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what are 2 reasons why you might not choose a PCN, cephalosporin, or carbapenem agent for a pt

1) beta lactam allergy 2) risk of seizures

What are the 4 drug factors that need to be considered when selecting an antimicrobial?

1- PK and PD 2- tissue penetration 3- drug toxicity 4- cost

What are the 7 host factors that need to be considered when selecting an antimicrobial?

1- allergy 2- age 3- organ function 4- metabolic abnormalities 5- pregnancy status 6- drugs 7- disease state

What are the 3 host factors that can cause a failure of antimicrobial therapy?

1- immunosuppression 2- surgical drainage of abscess or removal of foreign bodies 3- necrotic tissue

What are the 4 drug selection causes for failure of antimicrobial therapy?

1- inappropriate selection or dose or route 2- malabsorption 3- accelerated drug elimination 4- poor penetration to site of infection

What are the 3 reasons a person can have a fever?

1- infectious disease 2- a disease state that causes high temp 3- drugs that cause fever (b-lactam, sulfa, nitrofurantoin)

What are the 6 reasons we don't want to use non-preferred agents due to allergies?

1- inferior antibiotic efficacy 2- broad spectrum antibiotics 3- increase C. diff and MRSA 4- increase readmission 5- increase cost 6- increase adverse effects

traditiolnal dosing for aminoglycosides

1-2.5mg/kg IV Q*

What % of patients WITHOUT a penicillin allergy will have an allergic reaction to a cephalosporin ?

1-3%

what percent of patients w/o a penicillin allergy will have an allergic reaction to a cephalosporin?

1-3%

Vegetations: Bacteria within the vegetation grows _____ and protected from ______ and host _____

Slowly ABX and defenses

MRSA resistance: What is MecI?

Small DNA binding protein that prevents transcription and translation of PBP2a It is the repressor!!!

Mec-i

Small DNA-binding protein that prevents transcription and translation of PBP2a -repressor

What are the 1st Generation Cephalosporins active against?

Strep and staph little Gram Neg Rod coverage (Proteus, E. Coli, Klebsiella)

What is Piperacillin/Tazobactam cover?

Streptococci Enterococci Staphylococci (MSSA, MSSE) Anaerobes (including bacteroides) Excellent Gram Neg Coverage Covers Pseudomonas

What is Piperacillin/Tazobactam's coverage?

Streptococci (+), Enterococci (-), Staphylococci (+) - MSSA, MSSE -Anareobes including Bacteroides (-) -Excellent GNR coverage -Covers Psuedomonas (broad coverage)

What does Piperacillin/Tazobactam cover? (6)

Streptococci, Enterococci, Staphylococci, anaerobes, GNR, Pseudomonas

What do Cetriaxone and Cefotaxime cover? (2)

Streptococci, GNR

What do 2nd generation cephalosporins cover? (3)

Streptococci, MSSA, Increasing GNR coverage (HPEK)

What do 5th generation cephalosporins cover? (5)

Streptococci, Staphylococci, MRSA, Enterobacteriaceae, H. influenzae

What 3 things do Piperacillin/Tazobactam (Zosyn) cover?

Streptococcus Staphylococci Enterococci

What is Penicillin used for?

Streptococcus & Mouth flora -Strep Group A, B, C, G -Enterococcus (faecalis > faecium) -Streptococcus pneumoniae (increasing resistance) -Clostridium perfringens (necrotizing fascitis) -Peptostreptococcus

Gram + pairs

Streptococcus pneumoniae

Gram Stain--> Positive --> Cocci --> Pairs (diplococci) --> Pneumococci

Streptococcus pneumoniae

Which bacteria has increasing resistance to Penicillin?

Streptococcus pneumoniae (increasing resistance)

Gram Stain--> Positive --> Cocci --> Chains --> Streptococci--> Beta-hemolytic

Streptococcus pyrogenes Streptococcus agalactiae

Gram + chains b hemolytic (2)

Streptococcus pyrogens Streptococcus agalactiae

What does penicillin cover? (5)

Streptococcus, Enterococcus, Streptococcus pneumoniae, C. perfringens, Peptostreptococcus

What do aminopenicillins cover? (6)

Streptococcus, Enterococcus, Streptococcus pneumoniae, C. perfringens, Peptostreptococcus, H. influenzae

What are carbapenems relationship to Beta-lactamase?

Strong inducers

Why are carbapenems typically last line?

Strong inducers of resistance

Sulbactam

Sulfone group Nothing on L hand side

IE: patho of PVE/CDIE (early) what may directly inoculate the valve with bacteria from the patients skin of operating room personnel? Recently place ______ have greater susceptible to bacterial colonization than ____ valves

Surgery Nonendothelialized; native

What are the 3 breakpoints?

Susceptible Intermediate Resistant

Signs of IE: Osler nodes? Janeway lesions? Splinter hemorrhages? Petechiae? _____ of finger Roth spots? Emboli

Swollen, purple spots on finger/toes Hemorrhage on sole of feet and pains Specks on nails Red rashes, non painful Clubbing Hemorrhage on retina of eye

Unasyn: ______ irreversible B lactamase inhibitor Admin?

Synthetic IV and IM

Ampicillin and Sulbactam (Unasyn)

Synthetic Irreversible B-lactamase inhibitor Parenteral

What is the penicillin the DOC for?

Syphilis (T. pallidum)

Cefoxitin, Cefotetan, Cefuroxine (2nd generation) Covers most strep, MSSA T/F

T

t or f pseudomonas and capes bugs are often covered together

T

the 2 aminopenicillins (Ampicillin & amoxicillin) have similar activity to PCN T/F

T

What do "S" "I" or "R" mean next to a drug?

Tells whether the agent is Susceptible, intermediate, or resistant to treatments

What is BBW For fluoroquinolones? TQ**

Tendinitis

List the Tetracyclines

Tetracycline Doxycycline Minocycline

Definitive treatment

The "new" antibiotic for infection has been chosen as the best one for a patient based on test results (broad to narrow)

What's a breakpoint?

The MIC that is correlated with success so susceptible VS resistant

PCN V: What makes it PO available?

The ether next to the ring

What happens during an allergic reaction?

The mast cell that is primed comes in contact with the allergen which makes the mast cell release histamines and leukotrienes which causes the reaction

If a patient tests negative during their D-test, should you administer Erythromycin or Clindamycin?

The microbe is susceptible to clindamycin- you can send the patient home on clindamycin.

How are ring strain and allergy potential related?

The more ring strain, the more energy there is to be released when it is opened. The bigger the ring is, the less ring strain. Ring strain and allergy potential are directly related.

IE: what valve is affected with right sided?

Tricuspid

Healthcare related exposure is a HIGH risk factor for infective endocarditis A) True B) False

True

True/ False: All PCN classes cover Streptococcus

True

True/ False: Carbapenems are the most stable to B-lactamases

True

Which "quantitative testing" is the gold standard? A) Broth microdilution B) Etest C) Automation systems

A) Broth microdilution all of them test MIC

What is the first step when approaching a possible infection patient? A) Confirm presence of infection B) ID pathogen C) Selection of presumptive therapy considering every infected site D) More therapeutic response

A) Confirm presence of infection

MIC is high. Which drug should we use? A) Daptomycin B) Vanco

A) Daptomycin

Beta lactamase are considered what type of resistance? A) Energy independent drug degradation B) Energy dependent drug modification

A) Energy independent drug degradation Beta lactams requires NO ENERGY

Which macrolide is only used for GI MOTILITY? A) Erythromycin B) Azithromycin C) Clarithromycin

A) Erythromycin this drug causes prolong QTc

physical principles of blood flow based on pressure and resistance is describing? A) Hemodynamics B) Hematological C) Cellular changes D) Respiratory change

A) Hemodynamics

Which type of patient is at high risk of fungal endocarditis A) IVDA B) Immunocompromised C) HTN patient D) Prosthetic valve

A) IVDA B) Immunocompromised

What is NOT a contraindication for use of ANY BETA-LACTAM? A) Maculopapular rash B) SJS C) DRESS D) Acute interstitial nephritis

A) Maculopapular rash Note= all these you would not retry any BETA-LACTAM B) SJS C) DRESS D) Acute interstitial nephritis

Which valve is most commonly affected with infective endocarditis A) Mitral B) Aortic C) Tricuspid D) Pulmonary

A) Mitral B) Aortic Subacute= mitral valve Acute endocarditits= Aortic

Patient has STAPH endocarditis + MSSA on native valve. WHat drug and how long do we treat? A) Oxacillin 12 grams for 6 weeks B) Oxacillin 6 gram for 6 weeks C) Vancomycin 15 mg/kg IV for 6 weeks D) Cefazolin 2 g IV q8H for 6 weeks

A) Oxacillin 12 grams for 6 weeks

Patient has strep endocarditis on native (normal) valve. The MIC for penicillin is 0.12<x<0.5 . What is the treatment? A) Pen G plus Gentamicin for 4 weeks B) Pen G plus Gentamicin for 2 weeks C) Vancomycin for 4 weeks

A) Pen G plus Gentamicin for 4 weeks make sure to only use gentamicin in the first 2 weeks

What is the DOC for syphilis? A) Penicillin B) Aminopenicillins C) Penicillin resistant drugs D) Carbapenems

A) Penicillin

Which drug is #1 reported drug allergy? A) Penicillin B) Cephalosporins C) Monobactams D) Carbapenems

A) Penicillin

Which drug class is a "beta-lactams"? A) Penicillin B) Cephalosporins C) Monobactams D) Carbapenems

A) Penicillin B) Cephalosporins C) Monobactams D) Carbapenems ALL OF THEM

Which penicillin has POOR ACID STABILITY? A) Penicillin G B) Penicillin V

A) Penicillin G Notice= IM is a salt form

Which group is given prophylaxis therapy prior to dental procedure? A) Prosthetic valve B) Prior IE C) Cardiac transplantation D) Congenitial heart disease

A) Prosthetic valve B) Prior IE C) Cardiac transplantation D) Congenitial heart disease

Which ring is the "pharmacophore" for linezolid? A) Ring A B) Ring B C) Ring C

A) Ring A Ring B= Metabolism and Penetration (stability) Ring C= Solubility

Which organism is involved with Acute endocarditis? A) S. Aureus B) Viridans streptococci

A) S. Aureus

Gram positive cocci + POSITIVE catalase is what type of bacteria? A) Staphlyococcus B) Streptococcus

A) Staphlyococcus

Altering the target of bacteria will not respond to higher and higher dose of antibiotics? A) True B) False

A) True

Amoxicillin by itself has no anaerobic coverage, but when you add it with amoxicillin/clavulanate it will have anaerobic coverage including bacteroides? A) True B) False

A) True

Automated systems for detecting pathogens (bacteria) need both gram pos and gram neg panel and card selection to use machine? A) True B) False

A) True

Azithromycin or Clarithromycin is the best at treating atypical bacteria? A) True B) False

A) True

Beta lactamase inhibitors will have NOTHING HANGING of the left side of a beta-lactam ring? A) True B) False

A) True

Carbapenem is the most potent beta lactam? A) True B) False

A) True

Cefepime is 4th gen cephalosporin that can cover pseudomonas? A) True B) False

A) True

Cephalosporin with similar side chains to penicillin side chains will have a 5% chance of cross-reactivity ? A) True B) False

A) True

Disk diffusion only tells investigator if the antibiotic is "resistant or susceptible" but not intermediate? A) True B) False

A) True

Increase in Blood urea Nitrogen (BUN) and decrease urine output is associated with septic shock? A) True B) False

A) True

Inflammaion of the endocardium is called endocarditis? A) True B) False

A) True

Investigating if patient has "real allergy" and being able to "DE-LABEL" patients without a true allergy will help your patient get the best care? A) True B) False

A) True

Linezolid (Zyvox) can cause ADE of serotonin syndrome? A) True B) False

A) True

Mast cell degranulation can cause anaphylatic shock? A) True B) False

A) True

Metallo beta lactamases have increase activity against cephalosporins? A) True B) False

A) True

More ring strain with beta lactam drugs= higher potency? A) True B) False

A) True

Patient has had allergic reaction to penicillin, this patient may have INCREASE PROPENSITY TO DEVELOP ALLERGY to additional drugs (i.e any other drug)? A) True B) False

A) True

Pneumonia is typically strep pneumo? A) True B) False

A) True

Siderophore cephalosporins (Cifiderocol) is prescribed 7-14 days for kidney infections (pyelonephritis) A) True B) False

A) True

Staph and streptococci make up 75% of infective endocarditis A) True B) False

A) True

Streptococci viridans is most common strep with endocarditis A) True B) False

A) True

Sulbactam is a beta-lactamase inhibitor can also be used as the antibiotic? A) True B) False

A) True

Telavancin has longer half life than vancomycin? A) True B) False

A) True

Vanco, Linezolid, or Daptomycin can be used to treat ENTEROCOCCI bacteria? A) True B) False

A) True

Vancomycin is a TIME DEPENDENT MOA? A) True B) False

A) True

When treating IE, we stop doing blood cultures when it comes back negative? A) True B) False

A) True

Vancomycin can be characterized as " substrate denial" because blocks enzyme getting to its location (D-ALA D-ALA)? A) True B) False

A) True but it DOES NOT INHIBIT THE ENZYME IT IS TIME DEPENDENT MOA

Clavulanic acid or sulbactam will have two different attachments (covalent bonds) to beta-lactamase (enzyme) A) True B) False

A) True Serine on enzyme attacks ketone portion of drug (clavulanic acid) = opens ring Nucleophile on enzyme will attack michacalis menton rxn= this creates two different attachments

Beta lactams mimic D-alanine D-alanine segment in bacteria cell wall? A) True B) False

A) True This is how beta-lactams work

VISA can be characterized as adding a lot more glycopeptides ( D-ALA D-ALA ), which makes vancomycin less efficient at killing microbe? A) True B) False

A) True Vancomycin Intermediate staph aureus (VISA)

Vaborbactam (think of boron) will only react with serine protease? A) True B) False

A) True WILL NOT REACT WITH METALLO-PROTEASE Serine=attacks the boron

Base can break open a beta lactam ring? A) True B) False

A) True base can act like beta-lactamase

Combination therapy is used with antibiotics to prevent resistance? A) True B) False

A) True Kill organism before can create resistance

Methicillin has a unique structure which provides steric hinderance, which blocks beta-lactamase? A) True B) False

A) True note- methicillin has lower potency vs Pen G= is good, less affinity to penicillinase's

Daptomycin cannot be used for pneumonia? A) True B) False

A) True pneumona= use LINEZOLID

Every cephalosporin generation will NOT HAVE ENTEROCCI activity? A) True B) False

A) True **

Which anti MRSA drug has higher NEPHROTOXICITY A) Vanco B) Linezolid C) Daptomycin

A) Vanco

What type of stain technique is used to assess acid fast bacteria (TB)? A) Ziehl-Neelsen Stain B) India Ink C) Potassium hydroxide D) Giemsa stains

A) Ziehl-Neelsen Stain B) India Ink

Daptomycin has started to become resistant due to what gene mutation which adds lysine group to phopoholipid membrane on bacteria which prevents Daptomycin MOA? A) mprF B) yycG C) rpoC and rpoB

A) mprF

B lactamases: Classification? Which are most common in US?

A*** B C**** D

What is Delafloxacin the DOC for?

ABSSSI

IE: acute vs subacute Location/what valve?

AE: aortic SE: mitral

PBP2a (MRSA)

AKA MecA altered penicillin binding protein (like a 4x4 vehicle- moves slower but robust)

Beware of what with altered target?

Two component system!!!! They include a sensor, and an induced enzyme (alt target) that changes some biochemical pathway.

CRBI: risk factors Catheter factors? (4)

Type of catheter material Conditions of insertion Catheter site care Skill of the catheter inserted

Divergon

Type of gene (collection of genes) that turns on PBP2a

Divergon

Type of gene organization in which genes are divergently organized, thereby sharing regulatory elements, enabling co-regulation. This type of gene organization is often observed with a transcriptional regulator and its target genes or operon

3rd Gen penicillins

Typically not used Ticarcillin only one sorta used Some pseudomonas activity

common used for Bactrim

UTI, CA-MRSA, and pseumocistitis pneumonia

Penicillin

Upper respiratory Enterococcus Strep pneumoniae increase resistance C. Perfringes Peptostreptococcus DOC for syphilis Does not cover:bacteroides, gram -, or staph

What are 4th gen PCN? (4)

Ureidopenicillins Piperacillin Mezlocillin Azlocillin Big guns!!!!! No PO, expensive, last line, broad and potent

How are Ampicillin/sulbactam (Unasyn) and Amoxacillin/clavulanate (Augmentin) related?

Usasyn transitions to Augmentin (only oral)

Carapenem + B-lactamase Inhibitor

Used for complicated UTI Dose: 4g q8h INFUSED over 3 hours for 14 days ADE: Seizures, C.Diff, throbocytopenia, neuromotoe impairment

Monobactams (Aztreonam)

Used for gram neg only No gram + No anaerobes No cross reactivity with B-lactams

Daptomycin + Ceftaroline

Used in lab for MRSA May be a possiblity moving forward

What is reported being seen with Dapto resistance?

VISA resistance

B lactamase inhibitor: What are version 2.0? (3)

Vaborbactam Avibactam Relebactam

What are the 2 drugs that are reserved for MDR gram negative resistance?

Vabormere- meropenem/vaborbactam Recarbrio- Imipenem/cilastatin/relebactam

What was the result of the study evaluating Linezolid vs. Vancomycin for MRSA pneumonia?

Vanco has historically been DOC but linezolid was found to be better at penetrating into the lungs so it was better to use linezolid

first line for MRSA

Vancomycin could be pn, skin, meningitis, or even bacteremia

MRSA coverage

Vancomycin Telavancin Dalbavancin Oritavancin Linezolid Tedizolid Daptomycin Cetraroline TMP/SMX

CRBI: empiric ABX therapy GP? GN? Fungus?

Vancomycin GN option: Cefepime, Zosyn, carbapenems, +/- aminoglycosides Echinocandin for suspected candida

Staphylococcal endocarditis: native valve Oxacillin resistant tx?

Vancomycin 15 mg/kg IV q12h OR daptomycin >8 mg/kg QD x 6weeks

Staphylococcal endocarditis: prosthetic valve or other material Oxacillin resistant tx?

Vancomycin 15 mg/kg IV q12h PLUS rifampin 300 mg PO/IV q8h x >6weeks PLUS gentamicin 1 mg/kg IV/IM q8h x2weeks

Enterococcal endocarditis: PCN allergy tx?

Vancomycin 15 mg/kg q12h PLUS gentamicin 1 mg/kg IM/IV q8h x 6weeks Gentamicin resistant: use streptomycin same dose

Which Agents are our anti-MRSA agents?

Vancomycin, Linezolid, Daptomycin

What abx are anti-MRSA?

Vancomycin, Linezolid, Daptomycin, Telavancin

Surgery: need if.... Persistent _____ or increase size after prolonged tx _____ dysfxn ______ extension

Vegetation Valve Perivalvular

Dalbavancin (Dalvance)

Very long half life- lipoglycopeptide Dosed once on day one and then 8 days later

Gram Stain--> Positive --> Cocci --> Chains --> Streptococci--> alpha-hemolytic

Viridans Streptococcus Streptococcus pneumoniae (not to be confused with diplococcus)

Gram + chains a hemolytic (2)

Viridans streptococcus Streptococcus pneumoniae

What can the India Ink Stain be used for?

Virus

What are the Automated Systems for Quantitative Antimicrobial Susceptibility Testing? (Know them by name)

Vital Systems (Most common) MicroScan WalkAway System (Her favorite) Phoenix Sensititre

Automated MIC Systems Species identification complete in 3 hours 1. Vitek Systems (Vitek 1 and Vitek 2) 2. Microscan WalkAway System 3. BD Phoenix 4. Sensititre

Vitek

Automated MIC Systems Use small plastic cards 1. Vitek Systems (Vitek 1 and Vitek 2) 2. Microscan WalkAway System 3. BD Phoenix 4. Sensititre

Vitek

Automated MIC Systems susceptibility results in 15 hours 1. Vitek Systems (Vitek 1 and Vitek 2) 2. Microscan WalkAway System 3. BD Phoenix 4. Sensititre

Vitek

What are the 4 automated systems?

Vitek Microscan walkaway BD PHX Sensititre

Automated MIC Systems bioMerieux, Inc, Durham, NC 1. Vitek Systems (Vitek 1 and Vitek 2) 2. Microscan WalkAway System 3. BD Phoenix 4. Sensititre

Vitek Systems

What are the 4 automated systems?

Vitex Microscan walkaway BD Phoenix Sensititre

How can a WBW used in establishing the presence of an infection?

WBWs defend the body against invading organisms and will be elevated in response to an infection.

4th gen: piperacillin Spectrum similar to the 3rd gen but these are more potent on a ______ basis They are susceptible to what? Admin? Frequently combined with what?

Weight B lactamases IV or IM Aminoglycosides

For Utopiamycin: Well tolerated/ high side effects Limited Routes of administration/ Broad range of administration

Well tolerated and effective by all routes of administration

For Utopiamycin: Limited distribution in the host Widely distributed in the host

Widely distributed in the host

Carbenicillin

Withdrawn from market- nephrotoxic activity with pseudomonas

Does Cefepime (Maxipime) have good gram + coverage?

YES

penicillinase resistant drugs- Nafcillin, Methicillin, Oxacillin, Dicloxacillin Is it active against Streptococci?

YES

Is it okay to give Aztreonam with a penicillin allergy?

YES b/c not same class therfore no cross reactivity

Does penicillin cover Enterococcus ?

YES but has to be vancomyocin or penacillin susceptible

Are there any areas in the body that are sterile? If so, where are they?

Yes! -Bodily Fluids: synovial fluid, urine, spinal fluid -Tissues: bone, muscle, blood, connective -URT: kidneys & bladder **microbes isolated from these sites represent infections with potential for disease

What staining technique can be used for Acid Fast Bacilli? (Mycobacterium)

Ziehl Neelsen Stain

Determining Likely Pathogens (Direct Examination) What are other staining techniques? (4 of them)

Ziehl-Neelsen Stain India Ink (for fungi or mole or yeast) Potassium hydroxide (KOH) Giemsa Stains

Other stains

Ziehl-Neelsen stain: acid bacilli (myco) India ink: fungal KOH Giemsa: cytoplasmic/morphology

Which combination therapy product covers pseudomonas?

Zosyn - Piperacillin/ Tazobactam also has better GNR coverage

PCN G: What three structures are important?

Acid sensitive due to CH2 next to ring which makes the ring unable to protect the b lactam carbonyl Dimethyl are needed and most of the time cant add to them Carboxylic acid is essential!!!!

B lactamases: What are the acid/nucleophile for serine protease?

Acid: oxyanion hole Nucleophile: serine

What does Sulbactam cover?

Acinetobacter

What does Sulbactam have its own coverage against?

Acinetobacter (Oxidase-negative, Non-lactose fermenter, Gram-neg bacilli)

Avibactam

Active against ESBL (no metallo B-lactamase) in lab-not in practice Class A and Class C

What is the spectrum of Piperacillin?

Active against Haemophilus & many members of Enterobacteriaceae (E.Coli, Kleb) Active against Pseudomonas **Similar activity to ampicillin for Gram-positive **Uridopenicillin

What is the spectrum coverage of 1st generation cephalosporins?

Active against Strep & Staph (MSSA/E) Little GNR coverage: Proteus, E. Coli, Klebsiella **First gens only "PEK" the surface -- coverage gets deeper with each generation

Vegetations: It's formation destroy valvular tissue and continued destruction leads to acute ______ via ______ of valve leaflet Rupture of the ______ or _______ muscle Valve dehiscence in pt with _____

Acute HF Perforation Chordae tendineae or papillary muscle PVE

What is the group in piperacillin that tells us, we have pseudomonas activity?

Acyl- UREA **

IE: risk factors What other risk factors besides high risk and diseases? (5)

Advanced age Chronic IV access Cardiac implant device PWID Poor dental health

Gram - bacilli lactose fermenter oxidase positive (3)

Aeromonas Pasteurella Vibrio

Gram Stain --> Negative --> Bacilli --> Lactose Fermenter --> Oxidase positive

Aeromonas Pasteurella Vibrio

Host factors (6)

Allergy Age Organ failure Metabolic abnormalities Pregnancy Concomitant drugs or disease states

TQ** What are some Host Factors to consider when giving antibiotics?

Allergy Age Organ Function (do you need it renally dosed?) Metabolic abnormalities Pregnancy status Concomitant Drugs & Disease States

What is the clinical significance of acyl ureidopenicillins?

Allows penetration into pseudomonas! -still susceptible to beta-lactamases

List the Major Mechanisms of Resistance in order of decreasing levels of resistance:

Alterations of Target (most resistance) --> Energy Dependent Drug Modification --> Energy Independent Drug Modification --> Efflux Pumps (least resistance)

Vanco Resistant Enterococcus (VRE)

Altering one of the 5 D-ala groups in the cell wall - needs 5 d-ala to recognize bacteria

Amino glycoside coverage of Acinetobacter

Amikicin > tobra or gent

2nd gen PCN: aminopenicillins Special structure?

Amino group in side chain is protonated at physio pH. Positive charge provides acid stability which lessens likelihood of attack from B lactamases

Energy dependent drug modification examples:

Aminoglycosides

3rd gen PCN: ticarcillin Resistance develops rapidly so usually combined with an _______ Low resistance to normal B lactamases so combined with ______

Aminoglycosides Clavulanic acid

What is the drug of choice for Meningitis?

Aminopenicillin

What are the 2nd gen PCN? (3)

Aminopenicillins Ampicillin Amoxacillin All are PO with little GN

How are the PCNs and Aminopenicillins different?

Aminopenicillins cover -Haemophilus influenza (non-B-lactamase production) (-) -Slightly more active against Enterococci (DOC over PCN)

What is an example drugs classified as ribosome agent?

Amnoglycosides Oxazolinediones Tetracyclines Macrolides

What drugs are classified as aminopenicillins?

Amoxicillin & Ampicillin

Which agents are Aminopenicillins?

Amoxicillin & Ampicillin

Which is the DOC for Listeria monocytogenes?

Ampicillin

What are the 2 aminopenicillins?

Ampicillin Amoxicillin

Aminopenicillins

Ampicillin Amoxicillin NH2: acid stability- due to basic N -picks up proton in stomach acid pH--> picks up charge Better penetration w/ gram - Not protected against B-lactamases

Energy independent drug hydrolysis example?

B lactamase: hydrolysis requires no energy, so secreted enzyme, which has no access to energy, can remain active

Carbapenems are most stable to _____

B lactamases

What are the preferred agents for majority of inpatient infections?

B lactams

Which generation of cephalosporin covers anaerobic bacteria? A) 1st B) 2nd C) 3rd D) 4th

B) 2nd

Which generation of penicillins have more gram neg coverage and better oral availability? A) 1st gen B) 2nd gen C) 3rd Gen D) 4th gen

B) 2nd gen Aminopenicillins Ampicillin Amoxicillin

Which drug is effective at treating HAEMOPHILUS INFLUENZA non-beta lactamase production? A) Penicillin B) Amoxicillin C) Fluoroquinolones D) Nafacillin

B) Amoxicillin

Drug has a penicillin allergy, what drug should you NOT give? A) Cephalexin B) Amoxicillin C) Aztreonam D) Meropenem

B) Amoxicillin do not give drug in same class

Patient has ENTEROCOCCAL ENDOCARDITIS. What is the drug and length of treatment? A) Oxacillin 3 g IV q6H + Rifampin 300 mg IV q8H x 6 weeks B) Ampicillin 2 g IV + Gentamicin 3 mg/kg X 4-6 weeks C) Ampicillin 2 g IV + Ceftriaxone 2 g IV X 6 WEEKS

B) Ampicillin 2 g IV + Gentamicin 3 mg/kg X 4-6 weeks C) Ampicillin 2 g IV + Ceftriaxone 2 g IV X 6 WEEKS

What Element can stabilize Certain gram pos phospholipids within the peptidoglycan layer, making it more stable? A) Mg+2 B) Ca+2

B) Ca+2 Daptomycin disrupts (gets in the way) of Ca+2 interacting with bacterial membrane

Patient has penicillin allergy, what drug do we avoid? A) Cephalexin B) Cefoxitin C) Cefazolin D) Ceftriaxone

B) Cefoxitin note, will also avoid A) Cephalexin because WE ASSUME PATIENT DOESNT KNOW THE DIFFERENCE between penicillin allergy vs amoxicillin allergy

I have carbapenem-resistant Enterobacteriaceae. What drug should i use? A) Ceftolozane/tazobactam (Zerbaxa) B) Ceftazidime/Avibactam (Avycaz)

B) Ceftazidime/Avibactam (Avycaz)

Which drug has shown ADE's of increase CPK levels and decrease in nerve conduction? A) Vancomycin B) Daptomycin

B) Daptomycin

Bactrim covers pseudomonas? A) True B) False

B) False

Fastidious organisms do not need special nutrients for bacteria to grow? A) True B) False

B) False

Nonendothelialized valve are LESS susceptible to bacteria colonization vs normal valve? A) True B) False

B) False

Patients with PCN allergy will have an INCREASE risk of having CEPHALOSPORIN allergy? A) True B) False

B) False

Surgery removal of bacteria during endocarditis is 1st line treatment? A) True B) False

B) False

We can still give bactrim if patient is prego? A) True B) False

B) False

Beta lactamase are energy dependent, meaning they are not active until turn on? A) True B) False

B) False Beta lactamase are active right when they are secreted Enzyme that do phosphorylation (i.e kinases) are NOT active untill turn on by energy

5th gen cephalosporins (ceftaroline) covers pseudomonas and acinetobacter? A) True B) False

B) False Does NOT cover pseudomonas and acinetobacter It does cover MRSA

Colonization of bacteria is always treated? A) True B) False

B) False Infections= we treat

Linezolid (Zyvox) does not get absorbed from GI Tract? A) True B) False

B) False It does get absorbed= linezolid Does not get absorbed = vanco

Immature WBC will be more segmented with their nucleus? A) True B) False

B) False Mature WBC= Segmented

Beta-lactamase inhibitors are bacteriostatic? A) True B) False

B) False NOTE= THEY ARE ENZYME INHIBITORS= WHICH ALLOW DRUG TO ATTACK. THE DRUG= Bacteriostatic/cidal *****

Patient has penicillin allergy, we should use a broad spectrum antibiotic like fluoroquinolones because it has better outcomes for patient? A) True B) False

B) False Non-preffered agents (I.e broad spectrum antibitoics or anything thats not cephalosporin) is associated with WORSEN PATIENT OUTCOMES

Monobactams (Aztreonam) only treats GRAM POS? A) True B) False

B) False ONLY GRAM NEG!! No cross reactivity with BETA LACTAMS!!

Aztreonam only attacks GRAM + bacteria? A) True B) False

B) False Only GRAM -

You can overcome PBP2a with increased beta lactams? A) True B) False

B) False THE TARGET IS CHANGED.

VRSA MOA is by generating increase D-ALA D-ALA? A) True B) False

B) False This is describing VISA VRSA= Change D-ALA to latic acid or Serine

Maculopapular rash is considered an allergy (IgE mediated)? A) True B) False

B) False URTICARIA= IgE mediated allergy (i.e HIVES)

Patient who is in septic shock can still receive PO antibiotics? A) True B) False

B) False Wanna give IV

If bacteria is NOT sensitive to beta lactam drugs. Would you still prescribe ZOSYN? A) True B) False

B) False Zosyn= big guns for penicillin(best) but only works because of beta-lactam ring structure= if bug is not sensitive to beta lactam ring= DOESNT MATTER HOW MUCH ZOSYN, will not work

Monobactam is the most potent beta-lactam? A) True B) False

B) False has low ring strain= low potency

Vancomycin has high bioavailability? A) True B) False

B) False not bioavailable= this is why it is used in C. DIFF

Bacteria growth of MRSA is faster than MSSA? A) True B) False

B) False when gain resistance with PBP2a= it lost speed in crosslinking (i.e growth is slower)

Penicillin does not cover any anaerobes? A) True B) False

B) False It covers= peptostreptoccocus which is an anaerobe

Piperacillin/Tazobactam covers pseudomonas but not bacteroids? A) True B) False

B) False Pip/Tazo does cover bacteroides

Aminoglycosides (gentamicin, tobramycin, amikacin) only treat GRAM POS and ANAEROBES? A) True B) False

B) False Excellent GRAM NEG coverage and PSEUDOMONAS

Disk diffusion is a type of quantitative testing? A) True B) False

B) False Disk diffusion= qualitative testing

Only IgM mediated reactions are considered true allergy's A) True B) False

B) False IgE= true allergy

Ampicillin/Sulbactam (Unasyn) can treat psuedomonas? A) True B) False

B) False Pip/tazo covers pseudomonas

The 2 compartment method is what leads to VISA? A) True B) False

B) False leads to= Vanco Resistant Enterococcus (VRE)

Rhabdomyolysis is considered an "allergic reaction"? A) True B) False

B) False not an allergy

6 member ring has more ring strain vs 5 member ? A) True B) False

B) False 5 member ring has more stain= more likely to react with human immune system= more allergic (i.e penicillin) 6 member ring= cephalosporins= lessallergic because less ring strain

What is NOT considered a major criteria for Dukes definition of inefective endocardititis ? A) Blood culture positive for IE B) Fever greater than 38 celsius (100.4 F) C) Single pos BC for COXIELLA burnetii or anti-phase 1 IgG antibody D) Typical organisms consistent with IE from 2 separate BC

B) Fever greater than 38 celsius (100.4 F) 2 MAJOR CRITERIA= Definite IE 1 major + 3 minor= Definite IE or 5 minor criteria

How do aminopenicillins provide protection of the beta lactam ring in acid environment? A) Steric hinderance B) Has Amine group become + charged

B) Has Amine group become + charged note= still gets attack by beta lactamase

Patient has MRSA and VRSA (Vanco resistant staph A), What drug should you give? A) Vanco B) Linezolid

B) Linezolid

Which drug has ADE of serotonin syndrome? A) Vanco B) Linezolid C) Daptomycin

B) Linezolid

Beta lactam binds to MecR1 and causes what to happen? A) Bacteria can not cross link B) MecI is release from genes (transcription regulator) C) Creates PBP2a

B) MecI is release from genes (transcription regulator) than it will allow transcription of PBP2a

Beta lactamases must have a lewis acid and nucleophile to be effective. Which protease uses Zn+2? A) Serine protease B) Metallo protease

B) Metallo protease

Do we ever put energy in the periplasmic space? A) Yes B) No

B) No but we do put beta lactamases the small volume= makes high conentration of beta lactamases= drug dont work as well ONLY FOR GRAM NEG , Gram positive= we put beta lactamases outside cell so not as effective as working as gram neg= reason why old drugs work better with gram pos

MRSA is what type of protein? A) PBP2 B) PBP2a

B) PBP2a

Patient has strep endocarditis on native (normal) valve. The MIC for penicillin is less than 0.12. What is the treatment? A) Pen G plus Gentamicin for 4 weeks B) Pen G plus Gentamicin for 2 weeks C) Vancomycin for 4 weeks

B) Pen G plus Gentamicin for 2 weeks or just Pen g for 4 weeks or Just ceftriaxone FOR 4 weeks

Which classic penicillin can be taken orally? A) Penicillin G B) Penicillin V

B) Penicillin V Is still acid sensitive because 2 hydrogens off carbon but since Oxygen is there, it is less sensitive

Which bacteria is streptococcus + Beta hemolytic + positive bacitracin sensitive (making it GROUP A)? A) Streptococci Pneumoniae B) Streptococci pyogens C) Viridans Streptococci D) Streptococcus agalactiae

B) Streptococci pyogens neg bacitracin= group B= Streptococcus agalactiae

Gram positive cocci + Neg catalase is what type of bacteria? A) Staphlyococcus B) Streptococcus

B) Streptococcus

What bacteria would you NOT expect to find as infection in patients abdomen? A) Aerobic gram neg enteric B) Streptococcus C) Bacteroides D) Enterococcus

B) Streptococcus

Which aminoglycoside has stronger psuedomonas coverage? A) Gentamicin B) Tobramycin C) Amikacin

B) Tobramycin

Which type of echocardiogram is most INVASIVE and shows MOST INFORMATION? A) Transthoracic B) Transesphageal

B) Transesphageal note- NEGATIVE TEST DOESNT EXCLUDE inefective endocarditits

Energy independent drug hydrolysis B-lactamase

B- lactam hydroylsis requires no energy so secreted enzyme can remain active (breaks open 4 membered ring for energy)

PBP2a- MecA

B-lactam resistant PBP that allows for peptidoglycan cross-linking in the presence of all commercial B-lactams

What subclasses are there for metallo b lactamases?

B1 B2 B3

Vaborbactam

B=B-lactamase inhibitor B unhappy in molecule b/c it doesn't have octet but then gets charged--> unhappy Serine in active sit of B-lactamase fits in and bonds with B

Automated MIC Systems Becton, Dickinson & Company, Franklin Lakes, NJ 1. Vitek Systems (Vitek 1 and Vitek 2) 2. Microscan WalkAway System 3. BD Phoenix 4. Sensititre

BD Phoenix

Automated MIC Systems species identification complete in 4. 3hours 1. Vitek Systems (Vitek 1 and Vitek 2) 2. Microscan WalkAway System 3. BD Phoenix 4. Sensititre

BD Phoenix

Automated MIC Systems susceptibility results in 7.5-16 hours 1. Vitek Systems (Vitek 1 and Vitek 2) 2. Microscan WalkAway System 3. BD Phoenix 4. Sensititre

BD Phoenix

Automated MIC Systems also uses small plastic trays 1. Vitek Systems (Vitek 1 and Vitek 2) 2. Microscan WalkAway System 3. BD Phoenix 4. Sensititre

BD Phoenix + Vitek Systems

Are Beta-Lactams bacteriostatic or bactericidal?

Bactericidal Unless we don't have enough drug to kill all PBBs- then they are bactericidal at first

What is the difference between Bacteriostatic and Bactericidal?

Bactericidal= an agent that results in microbial death Bacteriostatic= an agent that inhibits more cell growth - associated with Minimum inhibitory concentration

For Utopiamycin: Bactericidal/ Bacteriostatic

Bactericidial- Dead cells do not mutate

What do Cefoxitin and Cefotetan cover? (1)

Bacteroides

What are the 3 things that penacillin DOES NOT COVER?

Bacteroides Gram - Staphylococci

What does Penicillin NOT cover?

Bacteroides Gram Neg Staphylococci

What does PCN NOT cover?

Bacteroides (-) Gram-negative organisms Staphylococci (+)

What does penicillin not cover? (3)

Bacteroides, GN organisms, Staphylococci

Metallo-B-lactamases

Bad news a OH is attracted to the Zn++ and acts as a nucleophile to open B-lactam ring in the antibiotic

Etest reads results from ___ of ellipse

Base

Why is the transpeptidase independent of energy?

Because it breaks one peptide bond (alannine) and adds a peptide bond (adding glycine to alannine)

ABs that cause "drug fever"

Beta lactams Sulfonamides Nitrofurantoin

Examples of Energy Independent Drug Modification

Beta-Lactamases ESBL, CRE

Why do bugs turn on PBP2a?

Beta-lactam antibiotics target PBP2.

Coverage of Azithromycin & Clarithromycin

Better Strep & Staph (+) coverage vs. erythromycin Better Gram-netgative coverage (Moraxella, H. influenza) Better atypical coverage

Ticarcillin

Bioisostere of carbenicillin More potent against pseudomonas Combined with sulbactam

Where are anaerobes commonly grown?

Blood

Why is Tazobactam a good agent?

Broad spectrum like sulbactam and good potency like clavulanic acid

What is unique about avibactam?

Broad!!! Class A, Class C and class A carbapenemases

Metallo b lactamases are especially worrisome due to: Their _____ activity profiles that encompass most ______ ABX, including what? Potential for _____ transference The absence of clinically useful _____

Broad; ceph; carbapenems Horizontal Inhibitors

Advantages of combo antibiotic therapy (3)

Broaden spectrum activity Synergism Preventing resistance

TQ** Antimicrobial Susceptibility Testing What are the 3 Minimum Inhibitory Concentration tests ?

Broth Microdilution E Test Automation Systems

Kinds of MIC (3)

Broth microdilution Etest Automation systems

IE: patho of PVE/CDIE (early) Bacteria also colonize the new valve from contaminated what? (4)

Bypass pumps Cannulas Pacemakers Nosocomial bacteremia subsequent to an IV catheter

Increases anaerobic coverage (including Bacteroides) a. Ampicillin/ Sulbactam (Unasyn) b. Amoxacillin/ Clavulanate (Augmentin) c. Piperacillin/ Tazobactam (Zosyn) IV Form

a and b

Transpeptidase

a bacterial enzyme that cross-links the peptidoglycan chains to form rigid cell walls - what the B-lactam antibiotic attacks

Patient has STAPH endocarditis + MRSA on NATIVE valve. WHat drug and how long do we treat? A) Oxacillin 12 grams for 6 weeks B) Oxacillin 6 gram for 6 weeks C) Vancomycin 15 mg/kg IV for 6 weeks D) Cefazolin 2 g IV q8H for 6 weeks

C) Vancomycin 15 mg/kg IV for 6 weeks or can use Daptomycin above 8 mg/kg x 6 weeks

Patient has STAPH endocarditis + MSSA + type 1 PCN allergy on native valve. WHat drug and how long do we treat? A) Oxacillin 12 grams for 6 weeks B) Oxacillin 6 gram for 6 weeks C) Vancomycin 15 mg/kg IV for 6 weeks D) Cefazolin 2 g IV q8H for 6 weeks

C) Vancomycin 15 mg/kg IV for 6 weeks type 2 allergy= Cefazolin

Which bacteria is Streptococci (Chains) + Alpha hemolytic + neg optochin test? A) Streptococci Pneumoniae B) Streptococci pyogens C) Viridans Streptococci D) Streptococcus agalactiae

C) Viridans Streptococci is pos optchin test= S. Pneumoniae

common used for cefdinir

CAP and sunus infections

common use for cetriaxone and cefoxitan

CAP, meningitis, SBP, pyelonephritis

Dx work up: Labs? (3) >____ sets of BC drawn at different sites Imaging/tests? (2) ______ sensitivity studies if BCs positive Physical for _____ findings of endocarditis

CBC w/diff, UA, ESR 3 EKG & echo ABX Classic

IE: risk factors Diseases/conditions? (6)

CHD DM Acquired valv dysfunction (rheumatic heart disease) CHF HIV infection Mitral valve prolapse with regurgitation

1) High potency toward a broad range of pathogens. 2) Low toxicity toward the host 3) Bactericidal action (dead cells do not mutate) 4) No interference with natural body defenses against infection 5) Well tolerated and effective by all routes of administration 6) Widely distributed within the host 7) Non-allergenic 8) Specific in its action (no side effects) 9) Compatible with other anti-infective agents 10)No bacterial resistance 11) Cheap

Characteristics of an ideal abx

For Utopiamycin: New / Old On Patent / Off Patent Cheap / Expensive

Cheap, Off Patent, Old

What is an advantage of Automatic Systems?

Can do Large Batches

advantages and disadvantages of automatic systems

Can do large batches Increase work flow Vs. Cant capture everything Hard to pick up resistant strains

List the order of ring strain among the beta lactic ring structures from most to least:

Carbapenem -- Penam -- Cefem -- Monobactam

What does Ceftazidime/Avibactam cover?

Carbapenem-R

DOC for ESBL

Carbapenems

What is most stable to B lactamases?

Carbapenems

What is the DOC for Amp-c producing bacteria?

Carbapenems

What is the DOC for ESBL? (extended spectrum B lactamase). **TQ**

Carbapenems

What is the broadest spectrum class of ABs?

Carbapenems- but does not work for MRSA

3rd gen PCN: ticarcillin Bioisostere of ______ More potent against _____ Admin? What is a concern about admin? (3)

Carbenicillin PSA IV or IM: not acid stable Sodium load, electrolyte problems, platelet dysfxn

Discuss the B lactam ring

Carbonyl is attacked and opens ring Beta carbon wants to be 109.5 degrees but it is 90 degrees which adds strain

What are 3rd gen PCN? (5)

Carboxy/indanylpenicillins Carbenicillin Indanyl carbenicillin Phenyl carbenicillin Ticarcillin Pseudomonas activity!!!

What test do you run to diagnose an organism as aerobic or anaerobic?

Catalase test

Failure of antimicrobial therapy (3)

Cause by : Drug selection, host factors, or pathogens

ANY IGE MEDIATED PENICILLIN ALLERGY (OK TO USE WHICH CEPHALOSPORIN)

Cefazolin Cefuroxime Ceftriaxone Ceftazidime Cefepime

Approach to Cephalosporin use with a Penicillin allergy TQ What are the 5 cephalosporins you can use with a Penicillin allergy?

Cefazolin Cefuroxime ceftriaxone ceftazidime cefepime

What are the 6 Cephalosporin drugs?

Cefazolin Cephalexin Cefuroxime Ceftriaxone Ceftazidime Cefepime

What are the Cephalosporins?

Cefazolin Cephalexin Cefuroxime Ceftriaxone Ceftazidime Cefepime

What are our first generation cephalosporins?

Cefazolin (parenteral) & Cephalexin (oral) **mneumonic trick- all first gens have an "a" after Ceph/Cef (exception is Cefaclor)

What are the 1st generation cephalosporins? (2)

Cefazolin, Cephalexin

Prevention of IE: antimicrobial options Allergic to PCN or amp and unable to take PO therapy?

Cefazolin/Ceftriaxone 1 g IM/IV OR clindamycin 600 mg IM/IV

4th generation cephalosporins

Cefepime

What are the 4th generation cephalosporins? (1)

Cefepime

Good GNR coverage + Pseudomonas

Cefepime & Ceftazidime Piperacillin/ tazobactam Aminoglycosides Cipro & levofloxacin Aztreonam Mero, imi, doripenem (not for use in lungs though) Ceftazidime/ Avibactam Ceftolozane/ tazobactam

which 2 cephalosporins has pseudomonas coverage?

Cefepime (4th generation ) & ceftazidime

What is the 4th generation cephalosporin?

Cefepime (Maxipime)

What drugs are 4th generation cephalosporins?

Cefepime is the only 4th gen **It ends in "me) but has no "t" in it- so its just "me" (all by itself)

What are the siderophores cephalosporins? (1)

Cefiderocol

What is the newer cephalosporin?

Cefiderocol

What is the Siderophore Cephalosporins?

Cefiderocol (Fetroja)

What is the siderophore cephalosporin?

Cefiderocol (Fetroja)

If a patient has a true penicillin allergy what cephalosporin should they not get?

Cefoxitin

Penicillin Allergy (DO NOT USE WHICH CEPHALOSPORIN)

Cefoxitin

What are the 2nd generation cephalosporins?

Cefoxitin Cefuroxime Cefotetan (The furry fox is tan)

What are the two cephalosporins we dont wanna give if patient has penicillin allergy?

Cefoxitin Cephalexin

What 2nd generation agent(s) covers Bacteroides?

Cefoxitin & Cefotetan **I remember that 2/3 of the second gens start with "Cefo," Cefuroxime is the odd one out- so its not a "real" one and doesn't have bacteroides coverage

What are the 2nd generation cephalosporins? (3)

Cefoxitin, Cefotetan, Cefuroxime

What are the 2nd generation Cephalosporins?

Cefoxitin, Cefotetan, Cefuroxine

What are the 2nd generation cephalosporins?

Cefoxitin, Cefotetan, Cefuroxine

What agents are 5th generation cephalosporins?

Ceftaroline

What are the 5th generation cephalosporins? (1)

Ceftaroline

What is the 5th generation cephalosporin?

Ceftaroline

Good gram positive + MRSA

Ceftaroline (Teflaro)

Maintains gram - coverage -enterobacteriaceae -H. influenzae - DOES NOT cover Pseudomonas or Acinetobacter

Ceftaroline (Teflaro)

No anaerobes & no enterococcus

Ceftaroline (Teflaro)

What is the 5th generation cephalosporin?

Ceftaroline (Teflaro)

IF HAVE MULTI DRUG RESITANT FOR PSEUDOMMONAS, WE WANT TO USE WHAT?

Ceftolozane/tazobactam (Zerbaxa)

What are the 2 cephalosporins/B lactamase Inhibitor

Ceftolozane/tazobactam (Zerbaxa) Ceftazidime/ Avibactam (Avycaz)

What are the cephalosporin/ B-lactamase Inhibitors?

Ceftolozane/tazobactam (Zerbaxa) Ceftazidime/Avibactam (Avycaz)

NO pseudommonas coverage a. Ceftriaxone b. Cefotaxime c. Ceftazidime

Ceftriaxone & cefotaxime only ceftazidime has Pseudomonnas

HACEK endocarditis: What is tx? PCN allergy?

Ceftriaxone 2 g IV/IM q24h OR ampicillin 2 g IV q6h OR ciprofloxacin 500 mg PO q12h or 400 mg IV q12h x 4weeks Ciprofloxacin 500 mg PO q12h or 400 mg IV q12h x 4weeks

What are the 3rd generation cephalosporins? (3)

Ceftriaxone, Cefotaxime, Ceftazidime

What are the 3rd generation cephalosporins?

Ceftriazone, Cefotaxime, Ceftazidime ***Drugs ending in "me" or "ne" AND have a "t" (t for tres) in their name are third gens.

VISA related dapto resistance

Cell wall is thickened suggesting that it makes it harder to absorb the dapto through the cell wall -like a sponge

Ampicillin/Amoxicillin Allergy (DO NOT USE WHICH CEPHALOSPORIN)

Cephalexin

What are the 1st generation cephalosporins?

Cephalexin Cefazolin

What are the 4 beta-lactam drug classes?

Cephalosporins Penicillins Monobactams Carbapenems

What are the 4 classes of B lactams?

Cephalosporins Penicillins Monobactams Carbapenems

How is the SAR different between Cephalosporins and Penicillins?

Cephalosporins are not as potent- can manipulate positions 3 & 7 on cephalosporins.

How do we change the potency, spectrum of action, and selectivity of Penicillins?

Changing the left side chain -generally cannot hang things off dimethyl side chain

what are the atypicals

Chlamydia spp, legionella spp, mycoplasma pneumonia, and mycobacterium tuberculosis

What does cefiderocol treat?

Complicted UTI caused by -E. Coli -K pneumoniae -P. mirabilia -P. aeruginosa -Enterobacter cloacae complex

How do we dose Aminoglycosides? (based on PK)

Concentration-dependent bacteriCIDAL effects -use high dose, once daily to maximize peak:MIC ratio Aminoglycosides also possess a post-antibiotic effect (persistent suppression of organism growth after concentrations decrease below MIC) that appears to contribute to success of high-dose, once daily administration **Peak:MIC ratio

How do we dose Fluoroquinolones?

Concentration-dependent killing activity, but optimal killing appears to be characterized by AUC: MIC ratio

What are the 3 problems in Diagnosis of Infection?

Confabulating Variables Drug Effects Fever

What are problems in diagnosing infection? (3)

Confabulating variables (GAP or fill in blanks) Drug effects (what can mimic infection) Fever (autoimmune diseases or drugs)

What is the use of Penicillinase-resistant class?

Covers Staphylococci (+) DOC for MSSA (+) Active against Streptococci (+)

What is the common use of Zosyvn?

Covers psuedomonas

Polymyxin B Resistance

Coverts the charge on Phosphates Adds N to repel positive charge lipopolysacchrides (endotoxin) toxic to humans but isn't as potent due to change of charge

If patients have a PCN allergy, can they use beta-lactams?

Cross reactivity to cephalosporins is roughly 3-5%, but to carbapenems it is roughly 11%

Transpeptidation

Cross-linking

Determining Likely Pathogens (Direct Examination) What is the order of a Gram stain?

Crystal Violet Iodine De colorization Counter stain (safranin)

Monitor therapeutic response:

Culture & sensitivity--> utilized to streamline therapy & improve therapy Parameters used to diagnose the infection: -WBC & temp normalize -Patients complaints diminish -Radiograph improvement -Antimicrobial serum

How do you monitor therapeutic response ?

Culture and sensitivity (broad to narrow) WBC and temp go down Patient is feeling better Radiographic improvement Antimicrobial serum

Definitive Antimicrobial therapy

Culture-documented therapy

E. coli endocarditis. How do you treat? A) Cefepime + Tobramycin B) Piperacillin + Tobramycin C) Ampicillin D) Ampicillin + Gentamicin

D) Ampicillin + Gentamicin

Which DOC is used for ESBL or AMP-C bacteria? A) Penicillin B) Aminopenicillins C) Penicillin resistant drugs D) Carbapenems

D) Carbapenems

Which is the only fluoroquinolone that covers MRSA? A) Ciprofloxacin B) Levofloxacin C) Moxifloxacin D) Delafloxacin

D) Delafloxacin

Which CARBAPENEMS does NOT cover psuedomonas or enterococcus? A) Imipenem B) Meropenem C) Doripenem D) Ertapenem

D) Ertapenem

What type of stain technique is used to assess fungi? A) Ziehl-Neelsen Stain B) India Ink C) Potassium hydroxide D) Giemsa stains

D) Giemsa stains

Which test if elevated will help diagnosis sepsis or pneumonia in patients? A) Erythrocyte sedimentation Rate (ESR) B) C-reactive protein (CRP) C) Cytokines D) Procalcitonin (PCT)

D) Procalcitonin (PCT) A and B are test used for endocarditits ALL OF THEM are test for inflammatory markers

What was the result in the study evaluating Daptomycin vs. Vancomycin for MRSA Bacteremia with MIC > 1mg/L?

DAP was better Vancomycin had a SS clinical failure rate

Fluoroquinolone resistance

DNA gyros has been altered such that fluoroquinolone can no longer bind to the essential Mg+2.

PBP's (Penicillin Binding Proteins) are no longer sensitive to methicillin.

Describe MRSA

DNA gyrase has been altered such that the fluoroquinolones can no longer bind to the essential Mg+2 .

Describe fluoroquinolone resistance

Small peptidoglycan portion, contains periplasmic space

Describe gram negative

Thick wall of peptidoglycan

Describe gram positive

IE: conditions assoc with higher incidence of IE? (3)

Diabetes Long term HD Poor dental hygiene

Tx guidelines: Need firm ______ ID organisms (____ and ______) ____ dose, route?, ______ ABX _____ therapy is often required Repeat ____ until negative Duration of therapy?

Diagnosis C and S High; IV; bactericidal Combo BCs 4-6 weeks

DAB

Diaminobuteric acid (amino acid)

TQ** Antimicrobial Susceptibility Testing measures the diameter of the zone of inhibition

Disk Diffusion

this test just tells you if there is a zone of inhibition or not

Disk Diffusion

Qualitative antimicrobial susceptibility test

Disk diffusion

For Utopiamycin: Does interfere with natural bodys defenses against infection/ Does not inferfere with natural body's defenses against infection

Does not inferfere with natural body's defenses against infection

What is the D test?

Double Disk Diffusion

Patient who suspect of having community associated MRSA (CA-MRSA) whose susceptibility profile reports erythromycin -R and clindamycin-S

Double Disk Diffusion (D Test)

When would you complete a "D-Test"

Double Disk Diffusion: Patients who are suspected of having community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) whose susceptibility profile reports erythromycin-R (resistant) and clindamycin-S (susceptible)

What are the 10 drugs that don't need a renal adjustment? (DRACC LEMON)

Doxycycline Rifampin Azithromycin Ceftriaxone Clindamycin Linezolid Erythromycin Moxifloxacin Oxacillin Nnafcillin

What abx are tetracyclines

Doxycyline, Minoclyline, Tetracycline, Tigecycline

Precautions with Bactrim

Drug Interactions Dermatological reactions - SJS Do not give if patient is G6PD deficient, pregnant at term, or to newborn

What can cause failure of antimicrobial Therapy?

Drug Selection: -inappropriate selection by dose or route -Malabsorption -Accelerated drug elimination -Poor penetration to site of infection Host Factors: -Immunosuppression -Surgical drainage of abscess or removal of foreign bodies -Necrotic tissue Caused by pathogens: -resistance

Mechanisms of resistance-Alter porins

Drug can't diffuse into cell (Gram -)

Which type of "endocarditis" has characteristics of "improper technique, fastidious isolates, non-bacteria culprit, antibiotic given prior to culture"? A) Right sided B) Left sided C) Native Valve D) Prosthetic valve E) Culture negative

E) Culture negative

Gram - bacilli lactose fermenter oxidase negative (4)

E. coli Klebsiella Enterobacter Citrobacter

What do Siderophores cover? (5)

E. coli, K. pneumoniae, P. mirabilis, P. aeruginosa, Enterobacter

What are carbapenems the DOC for?

ESBL or Amp-C producing bacteria

What is Carbapenems the DOC for?

ESBL or Amp-C producing bacteria

What are carbapenems the DOC for?

ESBL, Amp-C producing bacteria

what are carbapenems used for?

ESBL, pseudomonas, polymicrobial infections or MDR suspected empiric TX

which 2 are increased in Bone infections? a. Erythrocyte sedimentation rate (ESR) b. C-reactive protein (CRP) c. Cytokines d. Pro-calcitonin

ESR and C reactive protein

Summary: What resistance usually result in lower levels of resistance, but because they usually result in some level of cross resistance, emerge rapidly and are particularly common adaptations

Efflux pumps

Major mechanisms of resistance? (4)

Efflux pumps (weak) Energy independent drug degradation (b lactamases) Energy dependent drug modification Alteration of target (most dangerous)

Daptomycin ADE

Elevation of CPK levels decreased nerve conduction

Inflammation of the _______ Infection of the heart _____ by various microorganisms

Endocardium Valves

Cefazolin and Cephalexin (1st generation) No activity against... what 2 things?

Enterococci Anaerobic

What does 1st gen cephalosporins NOT have activity against?

Enterococci Anaerobic

What do 1st gens not have activity against?

Enterococci (-) Anaerobic (-)

What does Ertapenem not cover? (3)

Enterococci, Pseudomonas, Acinetobacter

What do 5th generation cephalosporins not cover? (4)

Enterococci, anaerobes, Pseudomonas, Acinetobacter

What do 1st generation cephalosporins not cover? (2)

Enterococci, anaerobic

What does ampicillin cover? (2)

Enterococci, little E. coli coverage

What do 2nd Gen cephalosporins NOT cover?

Enterococcus

What do 2nd generation cephalosporins not cover? (1)

Enterococcus

What does Ertapenem not cover?

Enterococcus Pseudomonas (-) Acinetobacter (-)

What does Ceftazidime NOT Cover?

Enterococcus and Anaerobes

What does Ceftazidime not cover? (2)

Enterococcus, anaerobes

What are the 2 new tetracyclines?

Eravacycline Omadacycline

Which one DOES NOT cover Pseudomonnas? a. Imipenem/cilastatin b. Meropenem c. Ertapenem d. Doripenem

Ertapenem all the others cover Pseudomonnas.

What is different about Ertapenem from Imipenem, meropenem, Doripenem??

Ertapenem does NOT cover Pseudommonas, NO Acinetobacter, and NO enterococcus

What is the difference between [imipenem, meropenem, doripenem] and ertapenem coverage?

Ertapenem does not cover pseudomonas or acinetobacter

What are Carbapenems?

Ertapenem, Meropenem, Doripenem, Imipenem

Establishing the Presence of Infections What are other Tests? (there are 4)

Erythrocyte sedimentation rate (ESR) C-reactive protein (CRP) Cytokines Pro-calcitonin

What other tests can be used to indicate infection

Erythrocyte sedimentation rate (ESR) CRP Cytokines Procalcitonin (PCT)

List the Macrolides

Erythromycin Clarithromycin Azithromycin

What abx are macrolides?

Erythromycin, Azithromycin, Clarithromycin

Which agents are in the Macrolide class?

Erythromycin, Azithromycin, Clarithromycin **Have immune modulation/ anti-inflammatory e

macrolides

Erythromycin, azithromycin, clarithromycin

TQ** What are 2 antibiotics that you use to test for D Test ??

Erythromyocin resistant Clindamyocin susceptable

Gram Stain --> Negative --> Bacilli --> Lactose Fermenter --> Oxidase negative

Escherichia coli Klebsiella spp. Enterobacter spp. Citrobacter spp.

Pneumococcal resistance is a concern with what class?

Even with cephalosporin 3rd gens

What is the coverage of fluoroquinolones?

Excellent Gram-negative Coverage of pseudomonas varies** Coverage of strep varies** Moxifloxacin has anaerobic coverage Atypical coverage: microplasma, legionella, chlamydia

What is the general coverage for aminoglycosides?

Excellent Gram-negative coverage + Pseudomonas Variable pseudomonas, serratia, acintobacter** ADEs: nephrotoxicity, ototoxicity

What is iMLSb or D test

For pts suspected to have community acquired MRSA with erythromycin-R and clindamycin-S profiles. It is a test to determine resistance and susceptibility of the strains and to see whether a D or O is made. Based on the results will determine what antibiotic to give pt. D = no clindamycin O= clindamycin

Why is protein binding important in the antibiotic selection?

Free unbound protein rather than total protein is best correlated with antibiotic activity degree of protein binding may have important clinical consequences in pts

IE: Acute endocarditis (AE) ______ form Assoc with _____ and _____ Primary pathogen?

Fulminating High fevers and systemic tox S.aureus

What can the Potassium Hydroxide staining technique be used for?

Fungi

Avibactam-pictured & Relebactam

Funky ring- B-lactamase inhibitor

Precautions with Macrolides

GI reactions (Erythromycin is used for GI motility) Motilin receptor agonist Drug Interactions - CYP450 interactions QT prolongation

common used for cefotetan and cefoxitan

GI surgical prophylaxis

What does monobactam cover?

GN only

Classic example of antibiotic resistance: Discuss E.coli

GN pumps tend to have 3 parts. Inner membrane portion AcrB, periplasmic adaptor AcrA, outer membrane channel TolC

What do aminopenicillins not cover?

GN rods, Bacteroides, Staphylococci

What do aminoglycosides cover? (3)

GN, Pseudomonas (T>G), Serratia (G>T), Acinetobactor (A>T/G)

aminoglycoside coverage

GN, pseudomonas, and synergy with GP

What does bactrim cover? (5)

GNR, Enterobacteriaceae, Staphylococci, MRSA, weak Streptococci

What does Delafloxacin cover? (2)

GP + MRSA, GN

What does Telavancin cover? (1)

GP only

GP vs GN?

GP releases b lactamase and will protect neighboring bugs GN: b lactamase is confined to periplasmic space in between outer and inner membranes.

vanco coverage

GP, MRSA, staph, enterococci, Cdiff

What do Imipenem, Meropenem and Doripenem cover? (4)

GP, Pseudomonas, Acinetobacter, anaerobes

What does monobactam not cover?

GP, anaerobes

What do aminoglycosides not cover? (2)

GP, anaerobic

carbapenem coverage

GP: MSSA, strep, GN: pseudomonas, acinetobacter, anaerobes

What is the significance of adding Chlorine as R groups onto Penicillin

Gain oral bioavailability Get some beta-lactamase inhibition Penetration

HACEK endocarditis: What organisms?

H.parainfluenzae, H.aphrophilus Actinobacillus actinomycetemcomitans Cardiobacterium hominis Eikenella corrodens Kingella kingae

Ampicillin & amoxicillin is great coverage for ______ _____

Haemophilus Influenzae (non B-lactamase production)

Gram Stain --> Negative --> Coccobacilli

Haemophilus influenzae Moraxella catarrhalis

What do the Ampicillins cover?

Haemophilus influenzae (B-lactamase Negative) Very little E. coli slightly more active against Enterococci

What can fever tell you about the presence of an infection?

Hallmark of infectious disease. Can be a manifestation of disease states other than infection Drug-induced fever

What is unique about vaborbactam?

Has boron!!!!

Polymyxin B Sensitive molecule

Has positive charges on drug and it interacts with neg charge on phosphates

Is skin testing for PCN allergy effective?

He says it is not great.

Gram - bacilli coccibacilli (2)

Heamophilus influenzae Moraxella catarrhalis

IE: discuss the pathogenesis of IE via hematogenous spread?

Heart defect leads to pressure gradient across valve. Fibrin-platelet deposition (NBTE) leads to bacteremia/colonized fibrin-platelet deposit. Further deposition of thrombus leads to vegetation.

How do you establish Severity of Infection? (5 things) TQ**

Hemodynamic Changes Cellular Changes Respiratory Changes Hematologic Changes Neurologic Changes

How can we establish the severity of the infection?

Hemodynamic changes, Cellular changes, Respiratory changes, Hematologic changes, Neurologic changes

What are 3 fastidious organisms

Hemophilus influenzae Neisseria gonorrhea Steptococcus pneumoniae

If there are colonies inside ellipse for Etest what does that indicate?

Heteroresistant strains

Class A PBP

High Molecular Weight bifunctional enzymes that catalyze transglycosylation and transpeptidation in vitro.

Class B

High Molecular Weight mono functional transpeptidases

For Utopiamycin: High potency/ Low potency Narrow Range, Broad Range

High potency toward a brogue range of pathogens

type 1 allergic rxn

IGE mediated allergic rxn DO NOT GIVE ANY DRUG WITHIN THE SAME B-LACTAM CLASS

allergy vs intolerance

IGE mediated allergic rxn: anaphylaxis, hives rash, hypotension, brochospasm, or angioedema VS. ADRs or ADEs: stomach upset, N, "makes me crazy", rash, raother

Urticaria (Hives) vs. Maculopapular Rash

IGE mediated; raised from skin, painful/itchy, distinct wheals, rapid appearance, & blanching VS. NOT IGE mediated, flat, not painful, delayed apperance, non-blanching, & can be disease-related (often misclassified as penicillin allergy)

Piperacillin and Tazobactam

IM/IV Restores potency of Augmentin Broadest spectrum of combo

List the overall approach for Selection of Antimicrobials? Confirm the presence of infection

Identify the pathogen, Selection of presumptive therapy considering every infected site, Monitor the therapeutic response.

ECHO: when is TEE performed? (3)

If TTE(-) or ongoing suspicion of IE or intracardiac complications in patients with initial TTE(+) High suspicion IE despite initial TEE(-), then repeat TEE 3-5 days or sooner Repeat TEE after initial TEE(+) if clinical features suggest new intracardiac complications

Why do we worry about drugs that can turn on and off inducibility? (rather than being constitutively active?)

If it is inducible- we work about it being a two component system - needs a sensor to turn on production and two component systems are BAD

Streptococcal endocarditis: native valve PCN allergic: dose?

If type I: vancomycin 15 mg/kg IV q12h x 4weeks

What is the 90-60 rule?

If you have an infection that has an antibiotic that is susceptible to it (which we always want to use antibiotics that the pathogen is susceptible to), 90% of the time that antibiotic will work. But if an infection is resistant to an antibiotic then 60% of the time it will STILL WORK! (body's immune system picks up the slack)

A Hapten or allergen (penicillin for example) will bind to B cell receptor on plasma cells. The plasma cell will than release _____

IgE antibodies

what is type 1 allergy?

IgE mediated

As pharmacists, we are most concerned with _____ mediated (Type 1) allergic reactions.

IgE-mediated

What are the 2 drugs in carbapenems class that have a high risk of seizures?

Imipenem cilastatin

What abx are carbapenems?

Imipenem, Meropenem, Doripenem, Ertapenem

What agents are Carbapenems

Imipenem/ cilastatin Meropenem Doripenem Ertapenem

What are Carbapenems?

Imipenem/cilastatin Meropenem Ertapenem Doripenem

What are the 4 Carbapenems?

Imipenem/cilastatin Meropenem Ertapenem Doripenem

What are some reasons why we can get "culture negative" endocarditis? (4)

Improper isolation or ID technique Fastidious organism Non bacteria culprit ABX admin prior to culture

B lactamases: Class B?

Increase activity against cephalosporin Metallo proteases are class B!!!!

ADEs of Daptomycin

Increased CPK

What is the function of the oxygen linker in Penicillin V?

Increases oral bioavailability -still not a good agent, but better than Penicillin

IE: subacute endocarditis (SE) ____ form Occurs in preexisting ______ disease Primary pathogen?

Indolent Valvular heart disease Viridans streptococci

Augmentin: Clavulanic acid is a naturally occurring ______ B lactamase inhibitor from Streptomyces clavuligeris. It is a suicide substrate. Increased spectrum now includes B lactamase producing: ? (5)

Irreversible S.aureus, H.influ, Klebsiella spp., E.coli and Proteus spp.

Klebsiella pneumoniae carbapenemase (KPC)

KPC is a Beta-lactamase that is able to confer resistance to all Beta lactams including extended spectrum cephalosporins and carbapenems

Most sensitive membranes in a human?

Kidney Neurons Heart

Vegatation of bacteria on fibrin clots can become "systemic embolic", if this embolism leaves the left side of the heart. Which organs are affected?

Kidneys Brain Spleen

New Delhi metallo b lactamase?

Klebsiella pneumoniae carbapenemase (KPC) Carbapenem resistant enterobacteriaceae (CRE)

What is ampicillin the DOC for?

L. monocytogenes

Gram + bacilli large nonspore forming (1)

Lactobacillus

Gram Stain--> Positive --> Bacilli --> Large--> Non-Spore Forming

Lactobacillus

What does Ceftazidime Cover?

Less Gram + coverage Good GNR AND PSEUDOMONAS**

What is Cetazidime's coverage?

Less Gram-positive coverage Good GNR coverage + Pseudomonas coverage (different from Ceftriazaone/ Cefotaxime) Still no Enterococcus, anaerobes

Fluoroquinolone coverage of Strep

Levofloxacin & Moxifloxacin > Ciprofloxacin (weak)

Coverage of Strep is what for Fluroquinolones? a. Ciprofloxacin > Levofloxacin > Moxifloxacin b. Levofloxacin & Moxifloxacin > Ciprofloxacin

Levofloxacin & moxifloxacin > ciprofloxacin weak MNemoic : lauren coughs mostly after strep

which GQ has pseudomonas coverage?

Levofloxacin and ciprofloxacin

What is the nucleophile and lewis acid in serine proteases?

Lewis acid: Oxyanion hole Serine Nucleophile: Serine side chain: HOR

B lactamases: What are the acid/nucleophile for metallo proteases

Lewis acid: Zn Nucleophile: OH will attack carbonyl

Clindamycin

Lincosamide Covers Gram-positives (Strep, MSSA) & anaerobes No Gram-negative activity Toxin suppressive effects Commonly ASSOCIATED with C. difficle

When might Linezolid be superior to vancomycin? When might it be inferior?

Linezolid may be superior in pneumonia Linezolid may be inferior for cath-related blood stream infections (CRBSIs)

What targets are the most difficult targets to make more resistant, and so resistance develops more slowly, and to a lesser degree than for _____ and ____ targets

Lipid; nucleic acid and protein Lipids are particularly difficult to modify because of the intricate packing required for a fxnl lipid bilayer

What do cephalosporins have no activity against? (LAME) whats the one exception?

Listeria Atypicals: chlamydia, legionella, mycoplasma MRSA Enterococci Ceftaroline can fight mRSA

Gram Stain--> Positive --> Bacilli --> Small

Listeria Propionibacterium Corynebacterium Gardnerella

What is Ampicillin theDOC for?

Listeria monocytogenes

What is the pathogen that causes meningitis?

Listeria monocytogenes

Class C

Low Molecular Weight act mainly as D-D-carboxypeptidases. Implicated in the degree of cross-linking and the maturation of the cell wall but are not essential for peptidoglycan biosynthesis.

For Utopiamycin: High/ Low toxicity toward the host

Low toxicity toward the host

What is the Minimal inhibitory concentration?

Lowest concentration of a chemical that prevents VISIBLE growth of a bacteria

Vegetations: Septic emboli from right sided endocarditis lodge in _____ leading to what? Emboli from left sided vegetations commonly affect organs with what?

Lung; pulmonary abscesses High blood flow (kidney, spleen, brain)

Quantitative antimicrobial susceptibility test

MIC

what is the Qualitative test?

MIC

Limitations with MIC testing:

MIC only represents concentration of antimicrobial needed to inhibit visual growth of the most resistant cells within the tested bacterial population, there can be a small percentage of bacteria present within the large numbers at site of infection that are antimicrobial-resistant (Observed with vanco)

Outcomes with vancomycin may be poor when ________

MICs are elevated

Alteration of target examples:

MRSA

What do Imipenem, Meropenem and Doripenem not cover? (1)

MRSA

What does Imipenem, Meropenem, & Doripenem not cover?

MRSA

penicillinase resistant drugs- Nafcillin, Methicillin, Oxacillin, Dicloxacillin does not cover what 4 things?

MRSA Bacteroides gram - organisms Enterococci

What does Penicillinase-resistant agents NOT cover?

MRSA Enterococci Gram Neg organisms Bacteroides

What are the 4 bacterias that are NOT covered by penicillinase resistant drugs?

MRSA enterococci gram negative bacteroides

What are the 3 bugs that vancomycin can treat?

MRSA enterococcus spp C. diff

What does ceftaroline cover?

MRSA gram positive enterobacteriaceae H. influenzae

What do the Penicillinase-resistant drugs not cover?

MRSA (+ anaerobe) Enterococci (+ anaerobe) Gram-negative organisms Bacteroides

When might Daptomycin be superior to vancomycin?

MRSA bacteremia when MICs are high

What do penicillinase-R not cover?

MRSA, Enterococci, GN organisms, Bacteroides

What do anti-MRSA cover? (4)

MRSA, MSSA, Streptococci, Enterococci

Examples of altered targets? (3)

MRSA: PBPs are no longer sensitive to methicillin Fluoroquinolones: DNA gyrase has been altered such that the Fluoroquinolones can no longer bind to the essential Mg VRE

What are penicillinase-R the DOC for?

MSSA

What is Ertapenem used for?

MSSA Strep Good GNR Anaerobes

what does adding the beta lactamase i to an amino PCN cover

MSSA and GN anaerobes (gut) HPEK still has strep, mouth anaerobes and enterococci

what does nafcillin, oxacillin cover?

MSSA and streptococci

What are the 4 ertapenem cover?

MSSA/E Strep GNR anaerobes

What is the spectrum for Ertapenem?

MSSA/E Strep Good GNR coverage Anaerobes

What do the Ampicillins NOT cover?

Most Gram Neg Rods Bacteroides Staphylococci

What do 2nd generation cephalosporins cover?

Most Strep, MSSA Increasing GNR coverage (proteus, E. Coli, Klebsilla, Haemophilus)

What do 2nd gens cover?

Most Strep, MSSA Increasing GNR coverage - PEK + Haemophilus (intra-abdominal coverage)

Mechanisms of resistance-Alteration of target

Most dangerous b/c can not push dose

Lipid targets and Microbial Resistance

Most difficult targets to make more resistant, and so resistance develops more slowly and to a lesser degree than for nucleus acid and protein targets. -lipids are particularly difficult to modify because of the intricate packing required for a functional lipid bilayer

ampicillin & amoxicillin does not cover....

Most gram - rods Bacterioides Staphylococci

What do the aminopenicillins NOT cover?

Most gram-negative RODS Bacteroides (-) Staphylococci (+) ***Very little E. coli coverage, not for UTI

What are unique characteristics of carbapenems?

Most stable beta-lactamases, Klebsiella Carbapenemase, strong inducer of resistance

B lactam ring structures: List in order of most strain to least (most potent to least)

Most: carbapenem 2nd most: penam 3rd most: Cefe Least: monobactam

Colistin

Mostly active vs Gram - microorganisms Not absorbed in the GI tract Nephro & neurotoxicity ADE

what are the FQ with respiratory penetration?

Moxi, gemifloxacin, and levofloxacin

Which fluoroquinolone has anaerobic coverage?

Moxifloxacin **I remember it has anaerobic coverage instead of pseudomonas

4th Gen Penicillins

Much better against pseudomonas

Cefem ring structure

Much less ring strain w/ 4 & 6 membered rings fused Cefalosporins use

Monobactam structure

Muych less reactive narrow spectrum of activity can use with penicillin allergy

Transglycosylation

NAG & NAM ** hoola hoops Backbone

What do we lose and gain with the aminopenicillins?

NH2 group Gain: oral bioavailability Lose: protection to Beta-lactamases

Where is the nucleophile in a haptenization reaction?

NH2 on the HSA

Are non-IgE mediated drug intolerances or side effects drug allergies?

NO

does cefepime have anaerobe coverage?

NO

can you give dapto with dextrose

NO reconstiture with sterile H2o

Can ESR, CRP, Cytokines, & PCT diagnosis an infection?

NO! they indicate an inflammatory process is happening, but not specifically an infection

Does Tazobactam work on metalloproteases?

NO- avibactam only

-MSSA/MSSE -strep a. PCN b. Ampicillin/Amoxacillin c. nafcillin d. Unasyn (ampicillin/sulbactam) / Augmentin e. Piperacillin/Tazobactam (Zosyn)

Nafcillin

What is the DOC for methicillin susceptible S aureus??? (MSSA)

Nafcillin

Which PCN(s) do(es) not cover Enterococci?

Nafcillin

Which PCN(s) do(es) not cover Mouth anaerobes?

Nafcillin

MSSA coverage:

Nafcillin 1st generation cephs B-lactam, B-lactamase inhibitors Clindamycin Levofloxacin TMP/SMX

What are the penicillinase resistant drugs?

Nafcillin Methicillin Oxacillin Dicloxacillin

What is used for Penicillinase-resistance?

Nafcillin Methicillin Oxacillin Dicloxacillin

For the most part, ________ and ________ can be considered equally effective for MSSA.

Nafcillin and Cefazolin But in practice the better drug is Nafcillin

Staphylococcal endocarditis: native valve Oxacillin susceptible tx? What if PCN allergic?

Nafcillin or oxacillin 12 g/d IV in 4-6 divided doses x 6weeks If type I: vancomycin 15 mg/kg IV q12h x 6weeks If type II: Cefazolin 2 g IV q8h x 6weeks

Staphylococcal endocarditis: prosthetic valve or other material Oxacillin susceptible tx? What if PCN allergic type II?

Nafcillin or oxacillin 3 g IV q6h PLUS rifampin 300 mg PO/IV q8h x >6 weeks PLUS gentamicin 1 mg/kg IV/IM q8h x 2weeks Vanco or Cefazolin

Which drugs are classified as penicillinase-resistant?

Nafcillin, Methicillin (not around anymore), Oxacillin (rare), Dicloxacillin

Which abx are penicillinase-R?

Nafcillin, Methicillin, Oxacillin, Dicloxacillin

What targets are the easiest to change, and thus the most likely to become resistant to the greatest degree

Nucleus acid targets (particularly RNA)

Methicillin

OCH3 in ortho positions to create steric hinderance to protect against B-lactamase attack removed from market due to hepatotoxicity Lower potency for Gram + than Pen G No Gram - activity

Methicillin: Special structure?

OCH3 must be ortho and no CH2!!!!

Infection of the tricuspid valve less common but most occurring in what population?

PWID

What can the Giemsa Stain be used for?

Parasites

Zosyn: Used _____ only Spectrum of inhibition is similar to _____ with a potency closer to clavulanic acid. Spectrum?

Parenterally Sulbactam Broadest of any combo

WHat is the drug of choice for syphilis?

Penicillin

What is the DOC for Syphilis?

Penicillin

excellent coverage for Strep Group A,B, C, G

Penicillin

What are the Penicillins?

Penicillin Ampicillin Amoxicillin Pipercillin Nafacillin

What is immune priming?

Penicillin binds to B cell receptor on Plasma protein. Plasma Protein releases IgE antibodies. IgE antibodies bind to IgE Receptor on mast cells.

B lactamases: Class A?

Penicillinase and TEM type, broad spectrum enzymes Some, but not all inhibited by currently available b lactamase inhibitor

List the classes within Beta-lactams:

Penicillins: PCN, Aminopenicillins, PCNase resistant, Extended Spectrum PCNs, B-lactam/B-lactamase inhibitors Cephalosporins (1st-5th generation) Carbapenems Monobactam

In Gram Negative Organisms, where is the highest concentration of beta-lactamases?

Peri-plasmic space

Which PCN(s) cover pseudomonas?

Piperacillin & Zosyn

Which PCN(s) have GNR coverage?

Piperacillin & Zosyn cover MOST GNR Unasyn and Augmentin cover some GNR

GN endocarditis: Pseudomonas aeruginosa tx?

Piperacillin OR ceftazidime OR Cefepime PLUS tobramycin 8 mg/kg/d x 6 weeks (peak 15-20 and trough <2)

Which one has GREAT COVERAGE against Pseudomonnas? a. Ampicillin/ Sulbactam (Unasyn) b. Amoxacillin/ Clavulanate (Augmentin) c. Piperacillin/ Tazobactam (Zosyn) IV Form

Piperacillin/ Tazobactam (Zosyn) IV form

B lactamases: ESBLs are frequently _____ encoded. They are responsible for ESBL production frequently carry genes encoding resistance to other drug classes. Therefore, ABX options in the tx for ESBL producing organism are extremely limited. What genes are involved?

Plasmid TEM-1/2 and SHV-1

What is the Clinical Significance of Serine Protease type ESBLs?

Plasmid encoded!!! Can degrade penicillins & 3rd gen cephalosporins Continue to evolve

B lactamase inhibitors primarily active against what?

Plasmid mediated b lactamases

What is the newer aminoglycoside?

Plazomicin

What would we look for on a differential WBC?

Polymorphonuclear leukocytes (mature) / Neutrophil Bands (immature) Infection causes an increase in bone marrow production of neutrophils to fight off the infection but they are released prematurely (as bands) so we will see a "left shift" meaning more bands in the WBC Differential

Pen G

Poor acid stability DOC for syphilis Ineffective against most S. aureus

What are the disadvantage(s) to Penicillin G?

Poor acid stability - cannot be given orally **Food effects absorption

Lab findings?

Positive blood cultures

CRBI: diagnostic criteria?

Positive semi quantitive culture of the catheter tip (>15 cfu/plate) AND Same organism grow from at least one percutaneous blood culture

Properties of Utopiamycin: High ______ toward a broad range of pathogens Low _____ toward the host Bacter______ action No interference with natural body ____ against infection Well tolerated and effective by all routes of ____ Widely _____ within the host Non-______ ______ in its action Compatible with other _____ agents Cheap

Potency Toxicity Bactericidal Defenses Admin Distributed Allergenic Specific Anti infective

IE: risk factors High risk? (3)

Presence of prosthetic valve Previous endocarditis Healthcare related exposure

Daptomycin

Primarily Gram + Really long Carbon tail and reaches into lipid membrane to rip it apart COOH in center of ring bind to Ca++

PBP2

Principle target of penicillins in gram + organisms that is sensitive to most beta=-lactams

Prevention of IE: Highest risk cardiac conditions Presence of a _______ Prior diagnosis of ____ Cardiac transplantation recipients who develop what? CHD

Prosthetic valve IE Cardiac valvulopathy

Infection following surgical insertion of a prosthetic valve: What two types?

Prosthetic valve endocarditis (PVE) Cardiac device IE (CDIE)

What targets can be changed over time, and can result in high levels of resistance?

Protein targets (topoisomerases, metabolic enzymes) Selective pressure mutations must flow thru the central dogma of molec biology: DNA to RNA to protein

Gram Stain --> Negative --> Bacilli --> Non-Lactose Fermenter --> Oxidase negative

Proteus spp. Proficendia spp. Serratia spp. Morganella spp. Salmonella spp. Shigella spp. Stenotrophomonas Acinetobacter spp.

What does Ampicillin/Sulbactam and Amoxicillin/Clavulanate not cover? (1)

Pseudomonas

What does Ceftolozane/Tazobactam cover?

Pseudomonas

What is the coverage of 4th generation penicillins?

Pseudomonas

What do Ceftriazone and Cefotaxime NOT Cover?

Pseudomonas Enterococcus Anaerobes

Pipercillin

Pseudomonas IM/IV Big guns

3rd gen: carbenicillin 1st PCN with activity against ______ Not stable to general B lactamases but stable to those produced by what? (5) Req large doses and produced tox so has been replaced by what?

Pseudomonas Pseudomonas, enterobacter, morganella, proteus, providencia which usually fxn as cephalosporinases Ticarcillin

What do fluoroquinolones cover? (4)

Pseudomonas (C>L>M), Streptococci (L/M >C), atypical

What bacteria does Cipro have better coverage for over the other two?

Pseudomonas aeruginosa

Gram Stain --> Negative --> Bacilli --> Non-Lactose Fermenter --> Oxidase positive

Pseudomonas spp. Flavobacterium spp. Alcaligenes spp. Achromobacter spp. Moraxella spp.

What does bactrim not cover? (4)

Pseudomonas, Enterococci, anaerobes, atypicals

What do Cetriaxone and Cefotaxime not cover? (3)

Pseudomonas, Enterococcus, anaerobes

a. Ceftolozane/tazobactam (Zerbaxa) b. Ceftazidime/ Avibactam (Avycaz) TQ ** these 2 have GREAT activity against ______

Psuedommonas

ADE's associated with inappropriate utilization of non-preferred antibiotics due to penicillin allergy

Pts with previous allergic rxn may have increased risk to develop allergy to add. drugs. This is not explained by cross-reactivity, and we should continue to push for cephalosporin therapy when appropriate. ONLY Cephalexin and cefoxitin pose cross reactivity risk with penicillin allergy...thus cephalosporins are safe to use. Use of non-preferred agents due to allergy is associated with worsened pt outcomes such as : 1. inferior ABX efficacy 2. increased readmissions 3. increased costs 4. broad spectrum ABX 5. increased C. diff and MRSA 6. increased ADRS/ADES

safety issues with macrolide antibiotics

QT prolongation, CVD caution, electrolyte abnormalities

What is a Disk Diffusion Assay?

Qualitative Testing for antimicrobial susceptibility testing Measures the diameter of the zone of inhibition **last line option

Antimicrobial Susceptibility Testing Minimum Inhibitory Concentration is a ______ tests A. Qualitative Testing b. Quanitative testing

Quanitative

What is the gold standard for antimicrobial susceptibility testing?

Quantitative Testing- MIC- Broth microdilution

What is an Etest?

Quantitative testing for antimicrobial susceptibility -gives more exact numbers

Advantages of an automatic system?

Quick, cost effective for hospital (decreased labor, quick response, large amount of samples)

Establishing the Presence of Infections White Blood Cells (WBCs) are also elevated in non infectious conditions such as what 3 things?

RA Leukemia drugs like corticosteriods

WBC elevated in what other diseases

RA, leukemia, corticosteriods use

What other reasons could there be for WBCs to be elevated?

RA, leukemia, drugs (corticosteroids)

Carbapenem > Penam > Cefem > Monobactam

Rank potency of beta-lactams

What is an allergic Reaction?

Re using penicillin, penicillin will now bind directly to IgE Receptors on mast cells, causing Cross Linking to happen, the mast cell will release granules

Is the CH2 linker between the carbonyl and the aromatic ring on Pen G protective or susceptible to attack by beta-lactamases?

Readily hydrolyzed by Beta-lactamases

Oritavancin (Orbactive)

Really long t 1/2, only dose once/ day and has a dual MOA: 1) works on cell wall 2) works on membrane **Having a dual MOA could prevent resistance from occurring

If a patient tests positive during their D test, should you administer Erythromycin or clindamycin?

Remember, D test positive = Erythromycin-R and Clindamycin-S. However, if D-test is positive, then clindamycin is also resistant for this microbe and they should not be given clindamycin EVEN if a different test says they are susceptible to clindamycin.

Daptomycin resistance lysyl phosphatidylglycerol transferase

Replace Ca++ with lysine to satisfy the +2 charge--> dapto doesn't work

Mechanisms of resistance-energy dependent drug modification

Requires energy and does not allow outside of cell

TQ**** Failure of Antimicrobial Therapy(Reasons why antibiotics may fail) Caused by Pathogens 1. _____

Resistance

Nafcillin

Resistant to B-lactamases similar to methacillin Staph MSSA IV only Can cause neutropenia or phlebitis

IE: persons who inject drugs is at high risk for disease of the ____ side of the heart and tends to be younger ______

Right Male

B-lactam ring structure

Ring is strained Very reactive- can react with other proteins besides target

Penam ring structure

Ring strain with 4 & 5 member rings fused

Daptomycin resistance genes that might have mutated

RpoC and rpoB- subunits of RNA polymerase

Staphylococcal endocarditis: IVDA Mostly caused by ______ ____ valve frequently infected Oxacillin susceptible tx?

S.aureus Tricuspid Nafcillin or oxacillin (vanco if PCN allergic or oxacillin resistant)

moitoring for vanco

SCR, renal, oto tox, redman

SE tends to involve what valve? AE?

SE: mitral AE: aortic

History of any of these rxns ___,____, & _____ to a Beta-lactam should be treated as CI to therapy with ANY beta-lactam due to safety data

SJS/TEN, DRESS, & allergic interstitial nephritis (poor kids :( )

What were the results of the meta-analyses evaluating macrolides and mortality in ICU patients with CAP?

SS decrease in risk vs. non-macrolide pts

approved indications for tedizolid

SSTI

indicatiolns for linezolid

SSTI, blood, VRE, pna

What generations cover anaerobes?

Second

What is a serious side effect of imipenem?

Seizures

Failure of Antimicrobial Therapy Caused by Drug _____

Selection

PCN V: Synthesis? More stable to _____ so can be given orally

Semisynthesis: break up PCN G and add side chain Acid

Automated MIC Systems Thermo Scientific Trek Diagnositc Systems, Oakwood Village, OH 1. Vitek Systems (Vitek 1 and Vitek 2) 2. Microscan WalkAway System 3. BD Phoenix 4. Sensititre

Sensititre

Automated MIC Systems use conventional broth microdilution trays as dry plate -species identification and susceptibility in 18-24 hours 1. Vitek Systems (Vitek 1 and Vitek 2) 2. Microscan WalkAway System 3. BD Phoenix 4. Sensititre

Sensititre

MecR1

Sensor that detects drug and creates confirmational change to activate Zn metalloprotease

MecR1

Sensor that displays a penicillin reactive site on the outer surface of the gram positive membrane. When this site reacts with a penicillin, a conformational change activates a Zn metalloprotease. This metalloprotease is thought to be responsible for cleavage of MECi.

MRSA resistance: What is MecR1?

Sensor!!! Displays a penicillin reactive site on the outer surface of the GP membrane. When this site reacts with a PCN, a conf change activates Zn metalloprotease. This is responsible for cleavage of the repressor, MecI

What 2 disease states is PCT most studied in?

Sepsis pneumonia

What do our beta-lactamase inhibitors target?

Serine protease beta-lactamases Until we had avibactem, nothing targeted metallo-protease beta-lactamases

B lactamases: What type is ESBLs?

Serine proteases

what are the SPACE or CAPES bugs

Serratia Providencia Acinetobacter Citrobacter Enterobacter

Selection of presumptive therapy: 6 factors to consider

Severity & acuity of disease Host factors Drug factors Combo therapy Therapeutic response monitoring Antimicrobial failure

What can you induce from local signs regarding the presence of an infection?

Signs --> visually if infection is superficial Sxs --> refer to the organ system

Tedizolid phosphate (Sivextro)

Similar to linelozolid (oxazolidinone) but is not supposed to interact with serotonin (no Serotonin syndrome) and is once daily and comes in oral and IV (linezolid is only IV)

What areas of the body are colonized? (6)

Skin Oropharynx GI Genital Urinary Foreign objects

What are some areas where colonization of bacteria occur?

Skin Oropharynx GI Genitals

What are the areas of the body that are colonized?

Skin oropharynx (mouth) GI Tract Genetial Tract

Therapeutic outcomes: Fever subsides within _____ of initiating therapy Persistent fever indicates what? BC should be negative within a few _____

1 week Ineffective ABX therapy Days

TQ** What is important(ADVANTAGE) about combination therapy?

1) Broadening the spectrum of coverage 2) Synergism 3) Prevents resistance

What is the process for a Gram Stain? (review from micro)

1) Fixate with heat (clear) 2) Add crystal violet (blue) 3) Treat with iodine (both Gram + and - will look the same up until this point - purple) 4) Decolorize (gram neg will be clear, gram+ will hold the purple color) 5) Counter Stain with Safranin -Gram+ will be purplish blue, Gram- will be pinkish red

What is the disadvantages of the automatic systems?

can't capture every microbe

oritovancin monitoring

cannot have UFH for 5 days after giving it can also elevate INR

What is a disadvantage of Automatic Systems?

cant pick up certain resistant microorganisms or fastidious organisms

safety issues with oxazolidiniones

cant used MAO within 14 days can cause serotonin crisis linezolid myelosupression, thrombocytopenia, optic neuropathy

What is avycaz used for?

carbapenem resistance

What is the drug of choice for ESBL or Amp-C producing bacteria?

carbapenems

What is absolutely critical for activity in the SAR?

carboxylic acid

What are the 3 BBW for fluroquinolones?

cardiovascular: aneurysm, QTc prolongation, TDP tendinitis/tendon rupture myasthenia gravis

If a patient has a true IgE mediated penicillin allergy what are the 5 cephalosporins they can get?

cefazolin cefuroxime ceftriaxone ceftazidime cefepime

What are the 2 1st gen cephalosporins?

cefazolin cephalexin

cephalosporins

cefazolin cephalexin cefuroxime ceftriaxone ceftazidime cefepime

What are the 1st generation cephalosporins?

cefazolin, cephalexin

What is the 4th gen cephalosporin?

cefepime

fourth gen cephalosporins and their coverage

cefepime (BROAD) staph strep, GNR HNPEC, SPACE, and pseudomonas

What is the siderophore cephalosporins?

cefiderocol (fetroja)

This drug is used for complicated urinary tract infections (cUTI)/ pyelonephritis caused by. E coli, pneumoniae, P. mirabilis, P aeurginosa and Enterobacter cloacae complex

cefiduracol (Fetroja)

derivative of ceftazidime that possesses a catechol siderophore moiety

cefiduracol (Fetroja)

which cephalosporin has a disulfuram like rxn

cefotetan

Approach to Cephalosporin use with a Penicillin allergy TQ If there is a penicillin allergy, do not use ____ cephalosporin

cefoxitin

What are the 2 second gen cephalosporins that cover bacteroides?

cefoxitin cefotetan

What are the 3 2nd gen cephalosporins?

cefoxitin cefotetan cefuroxime

which ones cover Bacteroides? a. cefoxitin b. cefotetan c. cefuroxime

cefoxitin & cefotetan

What is the 5th gen cephalosporin?

ceftaroline

which cephalosporins have MRSA

ceftaroline

fifth gen cephalosporins and their coverage

ceftaroline similar to ceftriaxone, good staph, MRSA, GNR

cefiduracol (Fetroja) is a derivative of _____ that possess a catechol siderophore moiety

ceftazadime

Aztreonam does cross react with ______because they have the same side chain

ceftazidime

good gram - coverage + Psuedomonnas a. Ceftriaxone b. Cefotaxime c. Ceftazidime

ceftazidime

less gram + coverage a. Ceftriaxone b. Cefotaxime c. Ceftazidime

ceftazidime

which cephalosporins have pseudomonas?

ceftazidime and cefepime

if have a carbapenem resistant strain use... a. Ceftolozane/tazobactam (Zerbaxa) b. Ceftazidime/ Avibactam (Avycaz)

ceftazidime/ avibactam (Avycaz

What are the 3 3rd gen cephalosporins?

ceftriaxone cefotaxime ceftazidime

3rd generation cephalosporins

ceftriaxone, cefotaxime, ceftazidime

What are the 3rd generation cephalosporins?

ceftriaxone, cefotaxime, ceftazidime

third gen cephalosporins and their coverage

ceftriaxone, ceftazidime, cefdinir less staph better strep, GNR ceftazidime has pseudomonas

Great Strep coverage a. Ceftriaxone b. Cefotaxime c. Ceftazidime

ceftriazone and cefotaxime

second gen cephalosporins and their coverage

cefuroxime, cefotetan, cefoxitan MSSA, most strep, HPEK cefoxitan and cefotetan have anaerobic (bacteroides) activity

If a patient is allergic to ampicillin or amoxicillin what cephalosporin should they not get?

cephalexin

Approach to Cephalosporin use with a Penicillin allergy TQ If there is a amoxicillin or ampicillin allergy, do not use ____

cephalexin A for amoxicillin/ampicillin and A in cephalexin

For most institutions (hospitals) formularies, no cephalosporins other than ________ and ____ pose a cross reactivity risk w/ PCN allergy otherwise cephalosporins are safe to use with penicillin allergy!

cephalexin & cefoxitin

first gen cephalosporins and their covg

cephalexin and cefazolin staph, strep, little PEK

What are the 8 drug classes that have anti-pseudomonas coverage? (CAMPFIRE)

cephalosporins carbapenems (not ertapenem) aztreonam fluoroquinolones aminoglycosides polymyxins beta-lactam/ inhibitors

Only ______ w/ side chains similar to a _____ pose a risk for 5% _____-______

cephalosporins penicillin cross-reactivity

counseling points for FQ

chelation with antacids, calcium, and iron photosentitivity, tendon pain

What fluoroquinolones cover pseudomonas?

cipro

What are the 3 fluoroquinolones?

cipro levofloxacin moxifloxacin

what are some medications that can contribute to AKI

cisplatin, amphotericin B, polymycin, radiocontrast, vanco, cyclosporin, tacrolimus, NSAID, loop diuretics

If D test is negative we can send them home on ______ but we always need to ask lab to do D tests

clindamycin

which antibiotic has highest risk for cdiff

clindamycin has boxed warning but all can cause it

how can you differentiate gram positive clusters vs gram positive chains

clusters is staph (MSSA, MRSA) chains are strep

Normal pathogens that live inside of us is _____

colonization

What is vabormere used for?

complicated UTI including pyelonephritis

What is the indication for Cefiderocol (Fetroja) ?

complicated urinary tract infections (cUTI) / pyelonephritis

a True PCN allergy is ______ for therapy w/ any member of the penicillin class

contraindication

What does unasyn and augmentin cover? what are the 2 increases coverage for these drugs?

cover: staphylococci (MSSA, MSSE) increase: anaerobic (bacteroides) and gram negative (haemophilus, proteus, e.coli, klebsiella)

patients w/ previous allergic reaction may have increased propensity (likelihood) to develop ALLERGY this is not explained by ______, and we should continue to push for cephalosporin therapy when appropriate

cross reactivity

What is definitive therapy?

culture documented therapy

What are the 2 bugs that carbapenem is the drug of choice for?

extended spectrum beta lactamase AmpC producing bacteria

culture documented therapy a. prophylaxis b. empiric c. definitive

definitive

What are the 2 drugs that are reserved for gram negative resistance MRSA?

delafloxacin tigecycline

Fever can be a manifestation of _____ states other than infection

disease

Name a qualitative test?

disk diffusion

what is the qualitative test?

disk difussion

Cefoxitin, Cefotetan, Cefuroxine (2nd generation) A. Covers Enterococcus b. Does not cover Enterococcus

does NOT cover enterococcus

What are the 4 carbapenem drugs?

doripenem Imipenem meropenem ertapenem

tetracyclines

doxycycline minocycline tetracycline tigecycline

What are the 3 drugs and 3 gram negative bacteria that carbapenems have activity against?

drugs: Imipenem, meropenem, doripenem bugs: enterococcus, pseudomonas aeruginosa, acinetobacter baumanni

What 5 bugs do cefiderocol cover?

e coli K. pneumoniae P. mirabilis P. aeruginosa Enterobacter cloaecae

Carbapenems

ertapenem meropenem doripenem imipenem

which antibiotic increases gastric motility

erythromycin (not a preferred macrolide but good for gastroparesis)

interpret a positive D test

erythromycin induced clarithromycin resistance

Penicillin covers Enterococcus. a. faecalis > faecium b. faecium > faecalis

faecalis > faecium

Establishing presence of infection

fever signs symptoms

whats fidaxomycin

first line for Cdiff pO only

What does sulbactam have coverage againsts?

acinetobacter

sulbactam has covg against

acinetobacter

Ertapenem has... a. MSSA/MSSE b. Strep c. Good GNR coverage d. covers anaerobes e. all of above

all

What is the drug of choice for listeria monocytogenes?

ampicillin

What 2 drugs are slightly more active against Enterococci?

ampicillin amoxicillin

What treats haemophilus influenzae?

ampicillin amoxicillin

if a patient has an IgE Penacillin allergy, what antibiotics should you avoid?

ampicillin amoxicillin pipercillin nafacillin

What antibiotic do we use to treat Haemophilus Influenzae (non B-lactamase production) ?

ampicillin & amoxicillin

-H fluenzae -Mouth -anaerobes -enterococci -strep a. PCN b. Ampicillin/Amoxacillin c. nafcillin d. Unasyn (ampicillin/sulbactam) / Augmentin e. Piperacillin/Tazobactam (Zosyn)

ampicillin/amoxicillin

What are the 3 beta-lactamase/inhibitors?

ampicillin/sulbactam (unasyn) amoxicillin/clavulanate (augmentin) piperacillin/tazobactam (zosyn)

What does 4th gen cephalosporins not cover?

anaerobes

metronidazole coverage

anaerobes

What does 5th gen cephalosporin 4 bugs not cover?

anaerobes enterococcus acinetobacter pseudomonas

What one is a TRUE allergy? a. stomach upset b. nausea c. anaphylaxis d. rhabdomyolysis e. makes me crazy f. rash

anaphylaxis rash is ? (questionable )

What is a true allergy?

anaphylaxis hives (urticaria)

Histamine is a vasodilator and will cause what 3 things?

angioedema anaphylatic shock hypotension

Clinical Practice Applications collect susceptibility testing results, compiled as an _____

antibiogram

What is prophylaxis therapy?

antibiotic administration in patients who do not have evidence of infection

What is empiric therapy?

antibiotics administration in patients suspected of having an infection but lacking culture documentation

name some medications that can prolong QT

antifungal, antipsychotics, methadone, FQ

pharmacist intervention to triage allergies and ensure receipt of best available therapy supports good ____ ___practice

antimicrobial stewardship practice

when do you draw a level for extended aminoglycoside dosing

anytime between 6 and 14 hrs from the start of the infusion. This will determine the interval to dose the medication

What are the three components to the SAR for classic penicillins?

aromatic ring, beta-lactam ring, carboxylic acid and steriochemistry

Coverage also includes _____ for (levofloxacin, moxifloxacin, fluroquinolone) TQ**

atypicals

What does Tigecycline cover?

atypicals, enterococci (VRE), MRSA, S. pneumoniae

FQ coverage

atypicals, good GN,

What does Doxycycline, Minocycline and tetracycline cover? (6)

atypicals, rickettsia, spirochetes, malaria, MRSA, S. pneumoniae

metronidazole counseling

avoid alcohol even 3 days after, make sure not prego, metallic taste, finish all, can elevate INR

safety concerns with tetracyclines

avoid in kids under 8, breast feeding and pregnancy, cation interactions, photosensitivity

safety concerns with bactrim

avoid in prego, breast feeding, or sulf allergy monitor: can incr. INR for skin rxn or hemolytic anemia if G6PD deficiency, hyperkalemia!

DDI with macrolides

avoid simvastatin/lovastatin with clarithromycin/erythromycin due to 3A4

alot of people use this for penacillin allergy patients very expensive drug only gram - coverage

aztreonam

monobactam

aztreonam

What are the 2 other beta lactam drug classes that are okay to give to a patient that has a penicillin allergy?

aztreonam carbapenems

monobactam drug and role

aztreonam IV GN and pseudomonas can be used in beta lactam allergy

uses for dapto

bloodstream, endocarditis, SSTI

Cefazolin and Cephalexin are active against a. Strep b. Staph (MSSE, MSSE) c. both

both

Monitor Therapeutic Response Culture & Sensitivity are used too... a. utilized to streamline therapy b. improvement of therapy c. both

both

patients dont normally difference between PCN vs amoxicillin --> assume patient is allergic to ____

both

Interpretation. What are Breakpoints? A_______ is a chosen concentration (mg/L) of an antibiotic which defines whether a species of bacteria is susceptible or resistant to the antibiotic.

breakpoints

Meropenem and Vaborbactam (Vabormere) What is the drug drug interaction?

breakthrough seizures due to valproic acid

What is the DDI with vabormere?

breakthrough seizures= valproic acid

Ampicillin/ Sulbactam (Unasyn) Amoxacillin/ Clavulanate (Augmentin) Piperacillin/ Tazobactam (Zosyn) IV Form alll have ____ coverage b/c we add that B lactamase inhibitor

broader coverage

What covers atypicals? TQ**

fluroquinolones

What are the 3 aminoglycosides?

gentamicin tobramycin amikacin

aminoglycosides

gentamicin tobramycin amikacin

when do you draw an aminoglycoside level for traditional dosing

get trough 30 min before 4th dose and get peak 30 minutes after the 4th infusion is complete

What coverage does carbapenems have?

good positive coverage some gram negative

how might listeria present on gram stain?

gram + rods

Cefazolin and Cephalexin (1st generation) Have little ____ coverage (E. coli, proteus, Klebsiella) a. gram - b. gram +

gram -

aztreonam is more $$$ and different antimicrobial spectrum. Aztreonam is a. gram - coverage only b. gram + coverage only

gram -

Fluoroquinolones Ciprofloxacin, Levofloxacin, & Moxifloxacin have excellent activity against _____ activity

gram - activity

Monobactams (Aztreonam) 1. Has gram ___ activity only 2. No gram _____ 3. No _____ 4. No cross activity w/ B lactams

gram - activity only no gram + no anaerobes no cross activity with B lactams

how might Neisseria present on gram stain

gram - cocci

whats the gram stain/morphology of pseudomonas

gram neg bacilli non-lactose fermenter oxidase positive

whats the gramstain/morphology of e coli.

gram neg bacilli oxidase neg

what antimicrobial spectrum is aztreonam?

gram negative

What 2 bugs are covered by aminoglycosides?

gram negative pseudomonas

What 2 bugs are good coverage by ceftazidime?

gram negative pseudomonas

What does aztreonam cover?

gram negative only

whats the gramstain/morphology of staph aures

gram pos cocci coagulase positive

What is the only bugs that telavancin cover?

gram positive

What 2 bugs are not covered by aminoglycosides?

gram positive anaerobic

whats the morphology of strep pneumo

gram positive diplococci

Determining Likely Pathogens (Direct Examination) A ______ ___ can be done for CSF Fluids, pulmonary, blood, and others

gram stain

why dont we use chloramphenicol

gray syndrome

Fever

hallmark of infections can be b/c of other disease state or a "drug fever"

What are the 3 fastidious organisms?

hemophilus influenzae Neisseria gonorrhea Streptococcus pneumoniae

describe lipophilic drug properties

hepatic clearance, large Vd, clearance inchanged in sepsis, higher intracellular conc, good bioavalability

Imipenem ADE

highest affect on seizure threshold

When the granules are released from Mast Cells they contain immunodulators such as _______

histamine

Urticaria (_____) IgE mediated _______ from skin ______/itchy Distinct ______ with clear ______ ______ appearance _______ (when pressed the center of a red hive turns white)

hives raised painful wheals, edges rapid blanching

What is the reason for using fluoroquinolones?

if patient has a true penicillin allergy

What are the 5 carbapenem drugs?

imipenem cilastatin meropenem doripenem ertapenem

carabapenems

imipenem/cilastatin meropenem doripenem ertapenem

Left shift means have more _____ cells in differential and indicates infection a. immature b. mature

immature

when would you use adjusted body weight? whats the formula

in obese pt use 0.4(ABW-IBW)+IBW

Patients w/ previous allergic reaction may have _____ propensity to develop _____ to additional drugs

increased allergy

What are the 3 side effects of cefiderocol?

injection site reaction diarrhea constipation

Polymyxin B

injury to plasma membrane Baceterialcidal Used topically- sometimes in IV when desperate Not absorbed from the GI tract

History of any of the following (extremely rare) reactions to a B lactam should be treated as contraindication to therapy with ANY B-Lactam due to ______ What are the 3 exceptions?

lack of safety data 1- SJS/ Toxic epidermal necrosis 2- DRESS 3- Allergic Interstitial Nephritis

What is the advantages of the automatic systems?

large batches

describe hydrophilic properties

low bioavailability and Vd, renal elimination, low intracellular conc, increased clearance in sepsis

What is the minimum inhibitory concentration (MIC)?

lowest concentration of an antimicrobial that will inhibit the visible growth of a microorganism

what is the MIC

lowest concentration with no growth

What 2 are in a differential that increase in a viral infection ?

lymphocytes and monocytes

NOT IgE mediated a. Urticaria (Hives) b. maculopapular rash

maculopapular rash

can be disease related (viral infection) a. Urticaria (Hives) b. maculopapular rash

maculopapular rash

delayed appearance a. Urticaria (Hives) b. maculopapular rash

maculopapular rash

more diffusely dispersed on skin a. Urticaria (Hives) b. maculopapular rash

maculopapular rash

mostly flat a. Urticaria (Hives) b. maculopapular rash

maculopapular rash

non blanching a. Urticaria (Hives) b. maculopapular rash

maculopapular rash

not painful a. Urticaria (Hives) b. maculopapular rash

maculopapular rash

how do you calculate IBW

male 50kg+2.3 (in over 5 ft) female 45.5kg+ 2.3 (in over 5ft

these antibodies are IgE antibodies. The Ige antibodies will bind to IgE receptors on ___ cells

mast cells

Other meds that cause "drug fever"

methyldopa hydrocortisone antipsychcotics

anaerobics

metronidazole clindamycin

Automated MIC Systems susceptibility results in 20 hours 1. Vitek Systems (Vitek 1 and Vitek 2) 2. Microscan WalkAway System 3. BD Phoenix 4. Sensititre

microscan walk away system

Automated MIC Systems Species identification complete in 2.5 hours but may take up to 6-18 hours 1. Vitek Systems (Vitek 1 and Vitek 2) 2. Microscan WalkAway System 3. BD Phoenix 4. Sensititre

microscan walkaway

Myth or fact PCN-allergic patients must avoid all cephalosporins b/c of potential cross reactivity

myth

For the most part, _____ and ____ can be considered equally effective for MSSA

nafacillin and cefazolin

What 2 drugs are equally effective for MSSA?

nafacillin and cefazolin

What are the 4 penicillinase resistant drugs that cover staphylococci and active against streptococci?

nafcillin methicillin oxacillin dicloxacillin

all of the PCNs cover enterococcus except for

nafcillin and oxacillin

what is intrinsic resistance? give an example

natural resistance ex) antibiotic too big to penetrate cell wall of bacteria

what is colonization?

naturally occurring in the body

televancin warnings

nephro and fetal risk avoid with UFH

aminoglycoside toxicities

nephro and oto make sure trough is below 2 mcg/mL

What are the 3 disadvantages of combo therapy?

nephrotoxicity antagonism additive toxicities

What are the 3 side effects for aminoglycosides?

nephrotoxicity ototoxicity neuromuscular paralysis

What are the 3 side effects of vancomycin?

nephrotoxicity ototoxicity redman syndrome

toxicities associated with polymyxin

neuro and nephro

Establishing the Presence of Infections Bands (immature) = left shift a. neutrophils b. basophils c. eosinophils d. all of above

neutrophils

3rd generation cephalosporins have _____ risk of cross reactivity in patients w/ penicillin allergy

no

Does Ertapenem cover Acinetobacter or Enterococcus?

no

Does ertapenem cover pseudomonas?

no

are all rashes the same? are all of them allergies?

no

do you renal adjust clindamycin

no

penicillinase resistant drugs- Nafcillin, Methicillin, Oxacillin, Dicloxacillin does it cover MRSA?

no only nafacillin for MSSA

why is ertapenam a poor carbapenem

no covg of PEA pseudomonas, enterobacter, or acinetobacter

Aztreonam

no cross reactivity with penicillin allergy cross reactivity with ceftazidime not preferred if cephalosporin appropriate (only covers Gram -)

WBC elevated (Another way to determine if infection is present)

normal range 4500-10000 see a left shift (more immature cells than mature cells)

Carbapenems

ok to give with penicillin allergy expensive $$$ more broad spectrum (not preferred if cephalosporin appropriate)

which one has coverage against Acinetobacter a. Ampicillin/ Sulbactam (Unasyn) b. Amoxacillin/ Clavulanate (Augmentin) c. Piperacillin/ Tazobactam (Zosyn) IV Form

only Ampicillin/ Sulbactam (Unasyn) has coverage against Acinetobacter

Includes Staphylococci coverage (MSSA, MSSE) a. Ampicillin/ Sulbactam (Unasyn) b. Amoxacillin/ Clavulanate (Augmentin) c. Piperacillin/ Tazobactam (Zosyn) IV Form

only Ampicillin/Sulbactam (Unasyn). & Amoxacillin/Calvulanate (Augmentin)

What drug form of vancomycin cover c. diff?

oral

what are 2 antibiotics with single doses

oritavanin, and delbavancin

What antibiotic covers streptrococcus & mouth flora ?

penicillin

What is the DRUG OF CHOICE for syphillis ? (Treponema pallidum)

penicillin

____ covers peptostreptococcus

penicillin

what are the 5 penicillin drugs?

penicillin amoxicillin ampicillin piperacillin nafcillin

penicillins

penicillin ampicillin amoxicillin piperacillin nafcillin

What is the #1 reported drug allergy in 10% of patients?

penicillin allergy

PBP2

penicillin binding site (like sports car... moves quickly to make cell wall)

What is the drug of choice for MSSA?

penicillinase resistant 4 drugs

Beta lactams

penicillins PCN aminopenicillins PCNase resistant extended spectrum PCNs B lactam/B lactamase inhibitors

What is the double disk diffusion (d-test)?

people with community associated MRSA tests for inducible macrolide lincosamide streptogamin B resistance (iMLSb) if the shape is D then don't give that drug either usually clindamycin and erythromycin

counseling points with bactrim

photosensitivity, finish all meds, drink lots of water, ask about sulfa allergy, confirm not prego or lactating

which PCN covers pseudomonas?

pip tazo

penicillin is not a protein but penicillin can break down & attach to our own ____ proteins

plasma proteins

Procalcitonin (PCT) is increased in ______ & ____

pneumonia & sepsis

What is the one sickness that daptomycin should stay away from and why?

pneumonnia its de-activated by lung surfactants

which antibiotics work on the cell membrane?

polymycin, daptomycin, telavancin, oritavancin

Imipenem, meropenem, Doripenem have good gram _____ coverage.

positive

Bacitracin spectrum of Activity

potent narrow spectrum antibiotic Mostly for Gram + cocci and bacilli

contraindicatns metronidazole

prego and alcohol

______ is produced by cells when there is injury to tissue and also produced in bacterial infections a. Erythrocyte sedimentation rate (ESR) b. C-reactive protein (CRP) c. Cytokines d. Pro-calcitonin

pro calcitonin

What are the 5 side effects for fluoroquinolones?

prolong QT tendonitis photosensitivity CNS GI issues

Antimicrobial therapy antibiotic administration in patients w/ no evidence of infection a. prophylaxis b. empiric c. definitive

prophylaxis

What are the 3 little gram negative coverage that 1st gen cephalosporins?

proteus e. coli klebsiella

Gram - bacilli non lactose fermenter oxidase negative (8)

proteus, serratia, salmonella, shigella, steno, acinetobacter, proficendia, morganella

What aminoglycosides has better coverage for pseudomonas? serratia? acinetobacter?

pse: tobramycin Ser: gentamicin Acin: amikacin

Gram - bacilli non lactose fermenter oxidase positive (5)

pseudomonas moraxella Flavobacterium Alcaligenes Achromobacter

What does zosyn cover that unasyn and augmentin don't cover?

pseudomonas streptococci enterococci

What are the 3 non-lactose fermenter gram negative bacteria?

pseudomonas aeruginosa acinetobacter baumannii stenotrophomonas maltophila

What is zerbaxa used for?

pseudomonas resistances

What does unasyn and augmentin not cover?

psuedomonas

what can we determine from a gram stain?

purple= gram + pink= gram - atypical will not stain morphology

Antimicrobial Susceptibility Testing Disk Diffusion is a ______ tests A. Qualitative Testing b. Quanitative testing

qualitative

Maculopapular _____ ____ IgE mediated not _____ more ______ dispersed on skin _____ appearance ___-_______ can be ______ related

rash not painful diffusely delayed non-blanching disease

What if the patient doesnt improve? Patients who fail to respond within 2-3 days require a thorough _____ ____

re-evaluation

Signs and symptoms of infection

redness depends where location of infection is (coughing, pus, etc.)

Mechanisms of resistance- efflux pumps

removes drug from cells

impenem associated w/ seizure particularly with ____ failure

renal

Carbapenems are strong inducers of ____

resistance

which antibiotics are DNA/RNAi

rifampin, quinolones, metronidazole, tinidazole

What is the side effects for meropenem and vaborbactam?

seizures CDAD thrombocytopenia neuromotor impairment

why do we avoid FQ

seizures, psych disturbances,tendon rupture, avoid in kids, QT prolongation, BG changes, photosensitivity, chelation, peripheral neuropathy

Automated MIC Systems which one takes longest to get identification and susceptibility? 1. Vitek Systems (Vitek 1 and Vitek 2) 2. Microscan WalkAway System 3. BD Phoenix 4. Sensititre

sensititre

a considerable body of evidence has established that PCN and cephalosporin cross reactivity is based on the _______ _____ structure and not the core Beta Lactam ring

side chain structure

cross reactivity occurs uncommonly, and only between molecules w/ similar R1 ____ ____

side chains

only cephalosporins with _____ chains similar to penicillin pose a risk for cross- reactivity

similar side chains to penicillin

what 4 areas of the body has colonization

skin oropharynx GI tract genital tract

Televancin uses

skin and soft tissure also HAP/VAP

common uses for tertacyclines

skin infections, acne, doxy: CAP, COPD exacerbations, STD, UTI, VRE

ampicillin & amoxicillin has... a. slightly more activity against Enterococci than PCN b. less coverage than Enterococci than PCN

slighty more coverage for enterococci than PCN

Hapten

small molecule that has to bind to a larger molecule to form an antigen

clindamycin coverage

staph, strep, and anaerobes

Nafcillin Methicillin Oxacillin Dicloxacillin covers _____

staphylococci

common used for cefazolin

surgical prophylaxis

what are some common indications for Bicillin l-a (penG benzathine)

syphilis given IM only!!

Antibiogram is percentage of strains susceptible to antimicrobial agent listed. t/f

t

Approach to Cephalosporin use with a Penicillin allergy TQ but if patient had cephalexin before and no problem you can use again t/f

t

Approach to Cephalosporin use with a Penicillin allergy TQ but if patient just has nausea or upset stomach, can use cephalexin t/f

t

Cefepime (Maxipime) has good GNR coverage and good gram positive coverage t/f

t

Cephalosporins as a class DO NOT cover enterococcus t/f

t

Clinical Practice Applications Understand discrepancies help distinguish between true resistance issues vs labortaory testing errors t/f

t

Depicition of Microtiter Plate is for gram - pathogens t/f

t

Duration of Therapy for Antimicrobials An individualized approach must be sought t/f

t

Duration of Therapy for Antimicrobials There are limited data describing the optimal duration of therapy t/f

t

Duration of Therapy for Antimicrobials When data are available, must be certain that patient fits the populations studied t/f

t

Establishing the Presence of Infections white blood cells are in 2 groups (granulocytes & agranulocytes) t/f

t

Etest methods have an ellipse and you read at the base of the ellipse. This is a Quantitative Testing t/f

t

Host Factors if someone has metabolic abnormalities may not absorb antibiotic as well t/f

t

Imipenem, meropenem, Doripenem has anareobe coverage t/f

t

Imipenem, meropenem, Doripenem has good gram - coverage and + , Pseudomonnas, and Acinetobacter t/f

t

Increasing resistance w/ GNR & anaerobes is a concern w 2nd cephalosporins & ampicillin/sulbactam t/f

t

Infection suspected ---> cultures obtained --> antibiotic initiated t/f

t

It takes 3-6 days to get cultures back t/f

t

Meropenem and Vaborbactam (Vabormere) is a Carbapenemn and B lactamase inhibitor t/f

t

No bactrum in later pregnancy stage t/f

t

Rectal fever is 0.6 higher in Celsius t/f

t

TQ* use of non-preferred agents due to allergy is associated w/ worsened outcomes t/f

t

There are various methods to detect organism and perform susceptibility t/f

t

We want complete zone of inhibition (circle) = which is D negative t/f

t

as a pharmacist, you ned to be an allergy detective and ask is this a true allergy (IgE Mediated or just an ADE?) t/f

t

ask: Has the patient previously received this abx w/ no issue? talk to the patient to clarify ambiguous allergy t/f

t

aztreonam is not preferred if cephalosporin is appropriate t/f

t

best way is temperature by oral t/f

t

carbapenems are more $$ and more broad spectrum ---> not preferred if cephalosporin is appropriate

t

carbapenems are okay to give with PCN allergy t/f

t

cephalosporin is gram - and gram + coverage t/f

t

example of similar side chains are Amoxicillin and cephalaxin t/f

t

if have IgE ceftriaxone allergy, do NOT give other cephalosporins t/f

t

if penacillin allergy, and patient has had cephalexin for example before with no issues, its okay to give again t/f

t

impienem can cause seizures t/f

t

many facilities have successfuly decreased carbapenem use just through better work up of PCN allergy t/f

t

similarly, carbapenems & aztreonam may be safely administered to these patients if use is appropriate t/f

t

so Imipenem, meropenem, Doripenem cover gram - and gram + t/f

t

What drug should NOT be given to a pregnant patient?

telavancin

tetracycline drugs and coverage

tetra, mino, and doxy cover CA-MRSA, VRE, S. pneumonia, atypicals, H.flu, moraxella, h. pylori, and rickettsai

What is immune priming?

the allergen attaches to a B cell which will then release IgE antibodies. The IgE antibodies will attach to a mast cell that has receptors for IgE. it is now primed

Susceptibility

the state or fact of being likely or liable to be influenced or harmed by a particular thing

What are the 2 side effects of linezolid?

thrombocytopenia serotonin syndrome

-Some GNR -Gut -anaerobes -MSSA/MSSE - H fluenzae -mouth -anaerobes -enterocci -strep a. PCN b. Ampicillin/Amoxacillin c. nafcillin d. Unasyn (ampicillin/sulbactam) / Augmentin e. Piperacillin/Tazobactam (Zosyn)

unasyn

blanching (when pressed, the center of a red hive turns white) a. Urticaria (Hives) b. maculopapular rash

urticaria

distinct "wheals" with clear edges a. Urticaria (Hives) b. maculopapular rash

urticaria

raised from the skin a. Urticaria (Hives) b. maculopapular rash

urticaria

rapid appearance a. Urticaria (Hives) b. maculopapular rash

urticaria

painful and itchy a. Urticaria (Hives) b. maculopapular rash

urticaria (hives)

IgE mediated a. Urticaria (Hives) b. maculopapular rash

urticaria which is hives

What are the 5 things that can happen to someone during an allergic reaction?

urticarial rash hypotension bronchospasm angioedema anaphylactic shock

quinprostine/dalfopristin

use with D5W in central line , not well toterated

Carbapenems have drug interaction with ______ ____

valproic acid

What is a DDI with carbapenems?

valproic acid

which antibiotics are area under the curve dependent

vanco

VISA resistance

vanco-intermediate S. aureas strains

What are the 4 drugs that can treat MRSA?

vancomycin daptomycin linezolid ceftaroline

What are the 4 anti-MRSA drugs?

vancomycin linezolid daptomycin telavancin

anti-MRSA

vancomycin linezolid daptomycin televancin tedizolid phosphate dalbavancin oritavancin

tigecycline coverage

very broad and good tissure penetration complicated SSTI, intraabdominal, and CAP

ampicillin & amoxicillin Does it cover E. coli coverage?

very little E coli coverage

What are the 4 automated system testings?

vitek systems microscan walkaway system BD phoenix sensititre

what factors must be taken into account in determining a proper antimicrobial dose?

weight site of infection route of elimination dosage selection

Establishing the Presence of Infections What defends the body against invading organisms?

white blood cells

Establishing the Presence of Infections What is elevated in response to infections?

white blood cells

use of non-preferred agents due to allergy is associated w/ _____ patients ______

worsening outcomes

do Piperacillin/Tazobactam (Zosyn) cover MSSA, MSSE?

yes

does Piperacillin/Tazobactam (Zosyn) cover Psuedomonas?

yes also E coli, preteus)

which one is betteR? a. Ceftolozane/tazobactam (Zerbaxa) b. Ceftazidime/ Avibactam (Avycaz)

zerbaxa

Pseudomonnas MOST Gram - coverage gut anaerobes MSSA/MSSE h fluenzae mouth anaerobes enterococci strep a. PCN b. Ampicillin/Amoxacillin c. nafcillin d. Unasyn (ampicillin/sulbactam) / Augmentin e. Piperacillin/Tazobactam (Zosyn)

zosyn

NO energy

β-lactam hydrolysis requires _______________, so secreted enzyme, which has no access to energy, can remain active.

dose vanco for Cdiff

125 mg QID X 10 days

target trough for vanco severe infections

15-20 mcg/mL

dosing for vanco

15-20 mg/kg Q 8-12 hrs

IV: PO conversion for oxazolidinones

1:1

IV: PO ratio metronidazole

1:1

IV:PO conversion with tetracyclines

1:1

Cephalosporins

1st gen: cefazolin, cephalexin 2nd gen: cefoxitin, cefotetan, cefurxoime 3rd gen: ceftriaxone, cefotaxime, ceftazidime 4th gen: cefepime 5th gen: ceftaroline Siderophere: Cefiderocol cephalosporins/b lactamases inhib: ceftolozane/tazobactam & ceftazidime/avibactam

What is the general trend in coverage within the generations of cephalosporins?

1st generations have little GNR coverage, but it increases throughout generations. Also begins covering pseudomonas and anaerobes

What is the dose of Meropenem and Vaborbactam (Vabormere)

4 g IV q8hr infused over 3 hours for 14 days (renally adjusted)

Beta lactam structure

4 member ring has highly strain bonds

name some common resistant pathogens

(kill each and every strong pathogen) klebsiella pneumonia, e. coli, acinetobacter, enterococcus faecalis, staph aures, pseudomonas aeruginosa

Beta-lactam ADEs

***Allergic reaction Interstitial nephritis (Zosyn- tubular malfunction) Seizures Thrombocytopenia Biliary sludging (ceftriaxone) Coagulopathy (cefotetan)

Mechanisms of resistance-Energy independent drug degradation

**if energy outside cell=independent*** Bug releases enzyme to destroy drug

<__% of patients w/ self reported PCN allergy have true IgE reaction

10%

For a patient WITH a penicillin allergy what is their percent risk of allergic reaction to ceftriaxone compared to a patient who is NOT pcn allergic?

-0.7%

For a patient w/ a penicillin allergy what is their percent risk of allergic reaction to ceftriaxone compared to a patient who is not penicillin allergic?

-0.7%

Combination Antimicrobial Therapy

-Broadening the spectrum of coverage -Synergism -Helps prevent resistance -Disadvantages: cost & potential for toxicity developing

Beta-lactamase inhibitors

-Combo products -Typically paired with aminopenicillins to block their breakdown since they are susceptible -Primarily against plasmid-mediated Beta-lactamases

If a patient has an infection- what would you expect to see then in the WBC?

-Elevated granulocyte counts, often with immature forms (bands) **mature neutrophils are sometimes called segmented neutrophils or polymorphonuclear leukocytes -With infection, can see WBC counts around 30,000-40,000 cells/mm3

Ampicillin/Sulbactam & Amoxicillin/Clavulanate

-Includes staphylococci coverage (MSSA, MSSE) -Increases anaerobic coverage (including Bacteroides) -Increases Gram Negative Rod (GNR) coverage: Haemophilus, Proteus, E.Coli, Klebsiella) -Does NOT cover Pseudomonas -Sulbactam has coverage against Acinetobacter

Two component system:

-Sensor, -induced enzyme (altered target) --> changes the biochemical pathway **Extremely dangerous

How do we select Presumptive Therapy?

-Severity and acuity of disease -Host factors -Drug factors -Combination Therapy -Therapeutic Response Monitoring -Antimicrobial Failure

What are the host factors to consider when starting therapy?

-allergies (type 1= anaphylaxis, type 2= just a delayed rash) -age -organ function -metabolic abnormalities -pregnancy status -concomitant drugs & disease states

What is PBPb2 and what is it's clinical significance?

-also called MecA -mutated PBP2 that causes methicillin resistance -resistance develops as a result of a B-lactam sensing protein, a transcriptional repressor, and a variant PBP2a

Efflux Pump -level of resistance -advantage(s)

-lower level of resistance because they result in some level of cross-resistance, energy rapidly, and are particularly common adaptations

Protein targets and Microbial Resistance

-topoisiomerases and metabolic enzymes -can be changed over time and can result in high level of resistance -selective pressure mutations and subsequent protein variants must flow through the central dogma of molecular biology: DNA --> RNA --> protein

bactrim dosing for uncomplicated UTI

1 DS tab PO BID X3 days

Approach for selection of antimicrobials

1. Confirm presence of infection 2. ID pathogen 3. Selection of therapy considering infection site (abs penetraitions differ) 4. Monitor therapeutic response

How do we determine severity of infection? (6)

1. Hemodynamic changes (vasodilation) 2. Cellular changes (glucose) 3. Resp. changes (metabolic alkalosis/acidosis) 4. Hematologic changes (PTT or ATT) 5. Neuro changes (decreased mental state or lethargic)

TQ**** Failure of Antimicrobial Therapy(Reasons why antibiotics may fail) Caused by Host Factors 1. _______ 2. Surgical drainage of ___ or removal of _____ ____ 3. _____ tissue

1. Immunosuppression 2. Surgical drainage of absess or removal of foreign bodies 3. Necrotic tissue

what are the worsened patient outcomes w/ Using Non-prefered agents 1. Inferior abx ______ 2. increased ______ 3. $$$ 4. _____- spectrum abx 5. increased ____ and _____ 6. ____ ADEs

1. Inferior abx efficacy 2. increased hospital readmission 3. $$$ 4. broad - spectrum abx 5. increased C diff and MRSA 6. increased ADEs

ID workup

1. Is infection present? 2. Test for microorgs 3. Considerations for antimicrobial therapy 4. F/U and monitoring 5. Streamlining therapy 6. DC

What are the 6 questions involved in an ID Workup?

1. Is there an infection present? 2. Testing for microorganisms 3. Considerations for antimicrobial therapy 4. Follow-up & monitoring 5. Streamlining therapy 6. Discontinuation

TQ** Selection of Presumptive Therapy What are the factors to be considered?

1. Severity and acuity of the disease 2. Host Factors 3. Drug Factors 4. Combination therapy 5. Therapeutic Response Monitoring 6. Antimicrobial Failure

Which of the 4 of automated MIC systems? TQ**

1. Vitek Systems (Vitek 1 and Vitek 2) 2. Microscan WalkAway System 3. BD Phoenix 4. Sensititre

4 classes of beta-lactams

1. cephalosporins 2. penicillins 3. monobactams 4. carbapenems

TQ**** Failure of Antimicrobial Therapy(Reasons why antibiotics may fail) Caused by Drug Selection 1. Inappropriate selection or ___ or _____ 2. ______ 3. _____ drug elimination 4. Poor ___ to site of infection

1. inappropriate selection or dose or route 2. Malabsorption 3. Accelerated drug elimination 4. Poor penetration to site of infection

Approach for Selection of Antimicrobials 1. Confirm the presence of ______ 2. Identification of the ______ 3. Selection of presumptive therapy considering every _____ site 4. Monitor _____ response

1. infection 2. pathogen 3. infected site 4. therapeutic response

Fluroquinolones can cause... 1. prolonged ___ 2. tendonitis/ tendon rupture/ achilles tendon rupture 3. _____ 4. CNS 5. Gastrointestinal (GI) ___, __, ___ 6. Drug interactions (decrease bioavailbility with multivalent cations)

1. prolonged QT 2. tendonitis 3. CNS 4. gastro issues like nausea, vomitting, diarrhea 5. drug interactions decrease bioavailability of multivalent cations

extended dosing for aminoglycosides

4-7 mg/kg Q24 bc conc dependent

Vancomycin Structure

2 Cl on aromatic rings... highly unusual

Vanco MOA

2 Vanco glycopeptide molecules create a sheet on D-Ala Carbohydrate "finger" inhibits transglycosolase

What is the dose for Cefiderocol (Fetroja) ?

2 grams IV infused over 3 hours every 6 hours for 7-14 days

After starting therapy, you should anticipate an improvement in _______ days.

2-3 days.

What is the dose for Cefiderocol?

2g IV INFUSED OVER 3 HOURS q6h x 7-14 days

Increasing resistance with GNR and anaerobes is a concern with what?

2nd generation cephalosporins and amp/sulb

If a or does not respond to an antibiotic in ___ days, a re-evaluation is needed

3

What 4 strep groups does penicillin have excellent coverage for?

A B C G

Two component systems

A type of signal transduction pathway commonly found in bacteria. - includes a sensor and an induced enzyme that changes the biochemical pathway Sensor=detects drug--> Response=usually alters target

What is a normal range in Celsius and Farenheit to not have a fever?

36.7- 37 C 98- 98.6 F

Standard Oral Fever Range

36.7-37 degrees C = 98-98.6 degrees F

Good GNR coverage:

3rd and 4th generation cephs Piperacillin/ tazobactam Fluroquinolones Carbapenems Aminoglycosides Aztreonam

Pneumococcal resistance is a concern even w/ ____ generation cephalosporins

3rd generation

what generation cephalosporins have lower risk of cross reactivity in patients w/ PCN allergy?

3rd generation

For reference, what is a normal WBC range?

4000-1000 cells/ mm3

if side chains are similar, there is a __% cross reactivity

5%

normal peak for aminoglycosides

5-10

zpack dosing

500 mg on day 1 then 250 mg on days 2-5

whats the dose of amoxicillin use for acute otitis media

90 mg/kg/day if using augmentin choose the one with lowest clavulante component

Clinical Practice Applications Infections caused by susceptible isolates respond to appropraite therapy 90% of the time whereas infections caused by resistant isolates respond to inappropriate antibiotic about 60% of the time

90-60 rule

what is the normal body temp for a human? F and C?

98-98.6 F 36.7-37 C

CRBI: duration of tx S.aureus? Enterococcus? GNR? Fungus?

>/= 14 days 7-14 days 7-14 days 14 days

90-60 rule

?

Per the Ambler B-lactamase Classification System: what class(es) is/are most common in the US?

A & C A = Penicillinases and TEM-type, broad spectrum enzymes C= Chromosomal cephalosporinases of GN bacteria

S.pneumoniae resistance: B lactam resistant strains of S.pneumoniae always harbor modified versions of their own class _____ and class _____ PBPs that are poorly acylated by B lactam

A and B

What is heteroresistant?

A few colonies that live can expand and grow a resistant strain

Pen V

A little bit more acid stable Can give orally- but have to give LARGE doses Reduced activity against gram -

What is the significance of epithelial cells in sputum specimens?

A predominance of epithelial cells in sputum specimens reduces the likelihood that recovered bacteria are pathogenic.

Energy Independent Drug Modification

B lactam hydrolysis requires NO energy, so secreted enzyme, which has no access to energy, can remain active.

Which chemical reactions require energy?

Acetylation phosphorylation adenylation

Energy Dependent Drug Modification

Acetylation, Phosphorylation, and adenylation ALL require energy to form the desired bond, and thus the enzyme is NOT active when secreted. Drug is functionally modified so that it is no longer able to bind to the target (which is still sensitive - meaning not changed).

Energy dependent drug modification example? (3)

Acetylation, phosphorylation, and adenylation Enzyme is NOT active when secreted

Energy

Acetylation, phosphorylation, and adenylation ALL require ________ to form the desired bond, and thus the enzyme is NOT active when secreted! Drug is functionally modified so that it no longer can bind to the (still sensitive) target.

PCN G: Poor ______ stability Dosing with ______ results in less decomposition Oral dose vs IV?

Acid Antacids Oral dose is 5x higher so not normally admin orally

Isoxazolyl PCNs: _____ stable so oral available as sodium salts _____ is most active and actually serves as B lactamase inhibitor Special tox?

Acid Dicloxacillin Oxacillin: hepatitis with prolonged use, neutropenia

Penicillin G structure- TQ

Acid sensitive due to 2H on C between ring and c=o No oral dosing

MRSA: The resistance is actually due to a group of genes that include what? (3)

B lactam sensing protein Transcriptional repressor Variant PBP2a that confers resistance

Enterococcal endocarditis: tolerate B lactam therapy What is tx?

Ampicillin 2 g IV q4h OR PCN 18-30 MU/d IV cont or 6 divided doses PLUS gentamicin 3 mg/kg IBW in 2-3 divided doses x4-6weeks OR Ampicillin 2 g IV q4h PLUS Ceftriaxone 2 g IV q12h x 6weeks

Prevention of IE: antimicrobial options Unable to take PO therapy?

Ampicillin 2 g IV/IM OR Cefazolin/Ceftriaxone 1g IM/IV

GN endocarditis: E.coli tx?

Ampicillin OR PCN OR broad spectrum cephalosporin PLUS aminoglycoside (genta) x6-8weeks

What abx are aminopenicillins?

Ampicillin, Amoxicillin

B Lactam / B lactamase Inhibitor Combinations What are the 3 drugs?

Ampicillin/ Sulbactam (Unasyn) Amoxacillin/ Clavulanate (Augmentin) Piperacillin/ Tazobactam (Zosyn) IV Form

What are the B-lactam/ B lactamase inhibitor combinations?

Ampicillin/Sulbactam Amoxacillin/clavulanate Ticarcillin/clavulanate Piperacillin/tazobactam

which one does NOT cover Pseudomonnas? a. Ampicillin/ Sulbactam (Unasyn) b. Amoxacillin/ Clavulanate (Augmentin) c. Piperacillin/ Tazobactam (Zosyn) IV Form

Ampicillin/Sulbactam (unasyn) Amoxacillin/ Clavulanate (Augmentin) only piperacillin/ tazobactam cover pseudamonnas

What does Bactrim NOT cover?

Anaerobes Atypicals Pseudomonas Enterococcus

what else does do Piperacillin/Tazobactam (Zosyn) cover?

Anaerobes, including Bacteroides

What does moxifloxacin cover? (1)

Anaerobic

Telavancin (Vibativ)

Anti-MRSA agent Gram-positive coverage only No anaerobic or gram-negative activity TERATOGENIC

Prophylaxis Antimicrobial Therapy

Antibiotic Administration in patients who do not have evidence of infection

Empiric Antimicrobial Therapy

Antibiotic administration in patients suspected of having an infection but lacking culture documention

Carbapenems are strong inducers of _____

B lactamase

IV drug user will get endocarditis, which valve is it typically infected? A) Mitral B) Aortic C) Tricuspid D) Pulmonary

C) Tricuspid

Prevention of IE: types of procedures? (2)

Any the require perforation of the oral mucosa Manipulation of the periapical region of the teeth of gingival tissue

What are the ADEs of Telavancin?

Appears more nephrotoxic than vancomycin! Prolongs QTc interval Interferes with clotting tests

What are sideophores the DOC for?

Complicated UTI, pyelonephritis

Follow up, monitoring, & streamlining (6)

Assess cultures & susceptibility results Streamlining Repeat cultures may be necessary Clinical cure (decrease symptoms/signs) Therapeutic drug monitoring Iv to po

Purpose of an echo?

Attempt to visualize vegetation's on heart valve

Which agent is active against some metalloproteases?

Avibactam

macrolide meds and coverage

Azithro, clarithro, and erythro atypical, h. flu, and s. pneumonia CAP and strep

Tazobactam

Azole ring- there to kill B-lactamase Nothing on left hand side

Monobactams

Aztreonam

What agents are classified as monobactam?

Aztreonam

What is the monobactam drug?

Aztreonam

What is the monobactams?

Aztreonam

Which abx is a monobactam?

Aztreonam

Quick overview of mechanism of B lactamase inhibiton?

B lactamase attacks carbonyl on b lactam ring and opens ring then a micheal acceptor is formed so that b lactamase will create permanent bond.

PCN degradation by what?

Nucleophile or b lactamase

If a patient has a penicillin allergy, it is contraindicated to giving any drug within the same _____ ______

B Lactam Class

What are the antibiotic workhorses?

B Lactams

Fever can be caused by drugs (drug-induced fever). What 3 drugs can cause fever?

B Lactams Sulfonamides Nitrofurantion

Patient has PROSTHETIC Valve + MSSA. What is drug and length of treatment? A) Oxacillin 3 g IV q6H X 6 weeks B) Oxacillin 3 g IV q6H + Rifampin 300 mg IV q8H x 6 weeks C) Oxacillin 3 g IV q6H + Rifampin 300 mg IV q8H x 6 weeks + 2 weeks of Gentamicin 1mg/kg q8H

C) Oxacillin 3 g IV q6H + Rifampin 300 mg IV q8H x 6 weeks + 2 weeks of Gentamicin 1mg/kg q8H If MRSA= just change oxacillin to Vanco **

We are estabalishing "presence of infection" from a fever variable. What drug is NOT causing drug fever? A) B-lactams B) Sulfonamides C) ACEi D) Nitrofurantoin

C) ACEi

What bacteria would you expect to cause infection in patients urinary tract? A) Aerobic gram positive B) Anaerobic gram neg C) Aerobic Gram neg D) Anaerobic gram positive

C) Aerobic Gram neg

Which drug is a monobactam? A) Cephalexin B) Amoxicillin C) Aztreonam D) Meropenem

C) Aztreonam

What is the hallmark lab value with diagnosis of Infective endocarditits? A) Anemia B) Increase C-reactive protein C) Blood culture D) Thrombocytopenia

C) Blood culture

Which drug is NOT expected to have cross reactivity with penicillin allergy? A) Cephalexin B) Cefoxitin C) Cefazolin D) Cefatrizine

C) Cefazolin

Psuedomonas endocarditis is treated with? A) Piperacillin B) Cefepime C) Cefepime + Tobramycin D) Piperacillin + Tobramycin

C) Cefepime + Tobramycin D) Piperacillin + Tobramycin TX for 6 weeks

What 3rd generation cephalosporin covers psuedomonas? A) Ceftriaxone B) Cefotaxime C) Ceftazidime

C) Ceftazidime

Patient has "HACEK" endocarditis + PCN allergy. What is the treatment? A) Ceftriaxone 2 g IV q24h X 4 weeks B) Ampicillin 2 g IV q6H X 4 weeks C) Ciprofloxacin 500 mg PO q12H x 4 weeks

C) Ciprofloxacin 500 mg PO q12H x 4 weeks if NO PCN ALLERGY= any of them will work

Patient needs prophylaxis therapy prior to dental procedure + PCN type 1 allergy. What is the treatment? A) Amoxicillin 2 g PO B) Ampicillin C) Clindamycin 600 mg PO D) Cephalexin 2 g

C) Clindamycin 600 mg PO

Which symptom is shown from endocarditis patients? A) Dyspnea B) Weight loss C) Fever D) Weakness

C) Fever

How many Hydrogen bonds must there be for vancomycin to work? A) Three H-Bonds B) Four H-Bonds C) Five H-Bonds

C) Five H-Bonds

Which drug class has ADE of tendon rupture and prolong QTc? A) Penicillins B) Cephalosporins C) Fluoroquinolones D) Monobactams

C) Fluoroquinolones

Patient has viral infection or TB. What WBC will be increased? A) Neutrophil B) Basophils C) Lymphocytes D) Eosinophils

C) Lymphocytes

Which drug is first line for treating BACTERIODES( ANAEROBES)? A) Cefepime B) Azithromycin C) Metronidazole

C) Metronidazole Say treating penumonia with Cefepime, notice bacteroides pops up= give METRONIDAZOLE

Which fluoroquinionlones cover anaerobic bacteria? A) Ciprofloxacin B) Levofloxacin C) Moxifloxacin

C) Moxifloxacin

Diagnosis of IE needs how many blood cultures? A) One B) Two C) Three

C) Three from different sites

What are the 3 body fluids that can be looked at through gram staining?

CSF fluid pulmonary blood

Augmentin

amoxicillin/clavulanate

Instead of having an amino group, if a penicillin has a CO2H group- what activity can be assumed?

CO2H group allows for penetration into pseudomonas. Also, not stable against beta-lactamases.

unique uses for azitromycin

COPD exacerbations and STDs and MAC prophylaxis

monitoring with dapto

CPK risk for myopathy and rhabdo

What is Meropenem and Varobactam the DOC for?

Complicated UTI including pyelonephritis

B lactamases: Class C?

Chromosomal cephalosporinases of GN bacteria

CRBI: risk factors Host factors? (8)

Chronic illness BM transplantation Neutropenia Malnutrition TPN admin Previous BSI Extremes of age Loss skin integrity

List the Fluoroquinolones

Ciprofloxacin Levofloxacin Moxifloxacin

Which agents are fluoroquinolones?

Ciprofloxacin Levofloxacin Moxifloxacin

FQs

Ciprofloxacin Levofloxacin Moxifloxacin delafloxacin

Fluoroquinolone pseudomonas coverage

Ciprofloxacin > Levlofloxacin > Moxifloxacin (none)

What is the coverage of Pseudomonas for fluroquinolones? a. Ciprofloxacin > Levofloxacin > Moxifloxacin b. Levofloxacin & Moxifloxacin > Ciprofloxacin

Ciprofloxacin > Levofloxacin > Moxifloxacin Clear Lake Mostly (mnemonic for psedummonas activity)

What abx are fluoroquinolones?

Ciprofloxacin, Levofloxacin, Moxifloxacin, Delafloxacin

Per Ambler B-lactamase Classification System: What class(es) is/are metallo-beta lactamases?

Class B: increased activity against cephalosporins

B lactamase inhibitor: What version 1.0? (2)

Clavulanic acid and sulbactam

Who standardized the MIC methods in the laboratory?

Clinical Laboratory Standards Institute- CLSI

Who standardized the MIC in the lab?

Clinical and Laboratory Standards Institute (CLSI)

Gram Stain--> Positive --> Bacilli --> Large--> Spore Forming

Clostridium Bacillus

Gram + bacilli large spore forming (2)

Clostridium and Bacillus

CRBI: what organisms? (5)

Coag negatives staph (31%) S.aureus (20%) Enterococci (9%) Candida species (9%) GNR (20%)

What is an antibiogram, and what is the cut off % when looking for idea agents to treat the pathogens?

Collection of susceptibility testing results, usually over a year period. Shows the balance between cost and effectiveness of each agent. Results over 80% are ideal

Colonization vs. Infection

Colonization is the presence, growth, and multiplication of the organism without observable clinical symptoms or immune reaction. Infection is abnormal or colonization gone wild and immune reaction/symptoms present.

Activity of B-lactamase inhibitors

Combo products Does not kill bacteria on its own Kills enzyme that tries to open B-lactamase NOT bacteria itself

Which PCN(s) covers Gut anerboes?

Combo products!- Unasyn Augmentin Zosyn

For Utopiamycin: Compatible with other anti-infective agents Non-compatible with other anti-infective agents

Compatible with other anti-infective agents

Meropenem and Vaborbactam (Vabormere) is used for what?

Complicated UTI including pyelonephritis

This test screen for inducible macrolide-lincdosamide streptogamin B resistance (iMLSb) TQ

D Test Double Disk Diffusion

Dont send home on clindamyocin susceptible if it is a. D positive b. D negative

D positive

What are the 2 only anti-MRSA antibiotics that are only given one dose?

Dalbavancin oritavacin

What fluoroquinolone treat acute bacterial skin and skin structure infections (ABSSSI)?

Delafloxacin

What is the newer fluoroquinolone?

Delafloxacin

What is Piperacillin?

Extended Spectrum PCN

What are a rapidly evolving group a b lactamases which shared the ability to hydrolyze 3rd gen ceph and aztreonam yet are inhibited by clavulanic acid?

Extended spectrum b lactamases (ESBLs)

In the Gram Positive Organisms, where is the highest concentration of beta-lactamases?

Extracellular environment

t or f ciprofloxacin has activity against strep pneumo

F

t or f you can use tigecycline in blood stream infections

F

t or f you need to renal dose adjust cefriaxone

F

t or f you need to renal dose ajust nafcillin, oxacillin, and dicloxacillin

F

T/F pts know the difference between penicillin vs amoxicillin allergy

F assume pt is allergic to BOTH

t or f you need to renal adjust moifloxacin

F dont use it in UTI

t or f PCN cover MRSA but not atypicals

F PCN do not cover either

t or f you can use daptomycin for pneumonia

F cannot use in lungs its inactivated by lung surfactant

t or F tigecycline has to be renal adjusted and has pseudomonas coverage

F for both

t or f carbapenems cover atypicals, VRE, and MRSA

F they dont cover any of these

True/ False: All PCN classes cover Mouth anaerobes

False- Nafcillin does not

True/ False: All PCN classes cover Enterococci

False- Nafcillin does not (but Nafcillin is DOC for S. aureus)

True/ False: Gram negatives never secrete a beta- lactasmase into the environment.

False- they usually do not, but it is not an absolute statement (potentially because there is porins in the outer membrane, it can be leaky to the outer environment)

True False: Eukaryotic and Prokaryotic cells have cell envelopes and peptidoglycan.

False: Eukaryotic cells do not have peptidoglycan.

True/ False: Augmentin is a competitive inhibitor

False: Irreversible Beta-lactamase inhibitor- suicide substrate

Automatic systems can analyze what 3 special organisms

Fastidious Anaerobes Mycobacteria

What does Fastidious mean? What are the fastidious organisms?

Fastidious: requires a specific environment to grow, more difficult to culture, susceptibility testing is difficult on these organisms -Hemophilus influenzae (-) -Neisseria gonorrhea (-) -Streptococcus pneumoniae (+)

What is the hallmark of infectious diseases?

Fever

Clinical presentation of IE: Sx? Signs? (2)

Fever Heart murmur, splenomegaly

When should you treat the patient until? (minimum)

First day of a negative culture

What is an example of a DNA targeting agent?

Fluoroqinolones rifampin

List the Aminoglycosides

Gentamicin Tobramycin Amikacin

Which agents are aminoglycosides?

Gentamicin Tobramycin Amikacin

Amino glycoside coverage of Serrate:

Gentamicin > tobramycin

What abx are aminoglycosides?

Gentamicin, Tobramycin, Amikacin

What is the coverage of Imipenem, Meropenem, Doripenem

Good G+coverage -MSSA/E -Strep - +/- for Enterococcus Good GNR coverage + Pseudomonas + Acinetobacter Anaerobes

What is cefepime used for?

Good Gram + -strep, MSSA Good GNR coverage PSEUDOMONAS

What is the coverage of Cefepime?

Good Gram-positive coverage -Strep -MSSA/E Good GNR coverage + Pseudomonas

What is the benefit of the Repository forms of Pen G?

Good for transient populations, STDs, non compliant populations, etc.

What are Imipenem Meropenem, Doripenem used for?

Good gram + -MSSA -Strep some Enterococcus Good GNR, Pseudomonas, Acinetobacter Anaerobes

What does Ceftaroline cover?

Good gram + **MRSA** Maintains GNR activity - Enterobacteriaceae -H. Influenza

What is the coverage of Ceftraoline?

Good gram-positive + MRSA (first cephalosporin for MRSA) Maintains GNR activity -Enterobacteriaceae -H-influenze

First stain performed

Gram

What do 1st Gen Penicillins Cover? (mostly)

Gram +

First Generation Penicillin used for?

Gram + MSSA

Vancomycin active against

Gram + & anaerobes MRSA agent Oral dose- C. Diff

serine protease related to ESBL

Gram - bacteria The plasmid is transmissible to other bacteria creates high molarity in periplasmic space

Piperacillin/Tazobactam (Zosyn) has excellent ____ coverage

Gram - coverage

Review- which agents produce beta-lactamases?

Gram Positive!!! -Gram Positive secrete Beta-lactamases into the environment, Gram negative keep them in periplasmic space

Efflux Pup:

Gram negative pumps have three parts: -inner membrane proton antiporter AcrB, the periplasmic adaptor AcrA, and the outer membrane channel TolC. *Acr comes from acriflavine resistance protein A and B.

Clavulanic Acid

Nothing hanging on left hand side of molecule O in 5 membered ring

2nd generations increase in ____ coverage

Gram-

What is the coverage for aztreonam?

Gram-negative ONLY No gram-positive No anaerobes No cross activity with Beta-lactams **can be used for people with penicillin allergies (less cross-reactivity)

What do Aminoglycosides NOT cover?

Gram-positive Anaerobic

What are the coverages of our anti-MRSA agents?

Gram-positive only -MRSA & MSSA -Strep -Enterococci **Vancomycin PO covers C. difficle (has to be PO- not absorbed systemically)

What do Ceftriazone and Cefotaxime Cover?

Great Strep Good GNR

What is the activity of Ceftriazone/ Cefotaxime?

Great Strep (+) coverage Good GNR coverage But NO pseudomonas (-) ,enterococcus, anaerobe coverage

what does HNPEK stand for

H. flu Neisseria Proteus E. coli Klebsiella

unique use for clarithromycin

H. pylori infection

Should you start antimicrobial therapy before or after taking a sample of the infected body material?

Infected body materials must be sample if possible or practical before starting antimicrobial therapy! -A delay in in obtaining infected fluids or tissues until after antimicrobial therapy is started might result in a false-negative culture or alterations in cellular and chemical composition of infected fluids

What are things to know about Meropenem and Varobactam?

Infusion over 3 hrs, breakthrough seizures

Linezolid MOA

Inhibit protein synthesis by binding to 50S subunit and preventing formation of the initiation complex.

MecI

Inhibitor or repressor that turns off PBP2a

Bacitracin

Inhibits cell wall synthesis by disrupting UPP which is a component of the flipase Bactericidal or bacteriostatic depending on organisms Refractory infections as Gram + organisms Oral occasionally used for treatment of pseudomembranous colitis

What are the ADE for Cefiderocol?

Injection site reaction Diarrhea Constipation GI

What are the ADEs of Cefiderocol (Fetroja) TQ****

Injection site reaction diarrhea constiptation other GI

Tx considerations: Large bacterial ______ _____ prevents WBC from confronting bacteria ABX only real tx and MAYBE _____

Inoculum Platelet fibrin network Surgery

Where are beta-lactamases in Gram - organisms?

Inside the periplasmic space

1. Efflux pumps 2. Energy independent drug degradation 3. Energy dependent drug modification 4. Alteration of target

Major mechanisms of resistance

What is colonization vs. infection?

Matter of circumstance Colonization is bacteria (normal flora) in a non-pathogenic state, like a normal area Infection is when the bacteria (or normal flora) becomes pathogenic Culture results do not identify only actual pathogens, must take into account severity of patients illness

PBP2a also known as what?

MecA

MRSA resistance: In the basal state, _____ constitutively blocks transcription of _____ and _____ genes as a dimer, while the ______ domain is zymogenic. If _____ detects B lactams in the extracellular space, it becomes acylated at its active site _____ residue. This triggers catalytic activation of the ______ domain, which faces the cytosol. The active protease induces proteolytic inactivation of _____ allowing the structural ____ gene to be produced, resulting in MRSA.

MecI; mecA and mecR1-mecI; mecR1-MP MecR1; serine; metallo protease MecI; mecA

What abx are carbapenem + beta-lactamase inhibitors?

Meropenem and Varobactam

What is the nucleophile and lewis acid in metallo-proteases?

Metal= lewis acid Nucleophile = hydroxide- OH-

B lactamases: What types?

Metallo proteases: Zn and OH Serine proteases: oxyanion and serine nucleophile

What are the two types of B-lactamases?

Metallo-proteases and Serine type proteases

Nafcillin: Special structure? (3)

Methoxy, ring structure and no CH2 so resistant to B lactamases

Why does methicillin has a risk of hepatotoxicity?

Methyl groups on the aromatic ring can be metabolized to formaldehyde-- we replaced them with ethyl groups on Nafcillin and no longer had risk of hepatotoxicity

Good Anaerobic coverage:

Metronidazole Clindamycin B-lactam/B-lactamase inhibitor Carbapenem Cefoxitin & Cefotetan

Anaerobic agents

Metronidazole & Clindamycin

What abx are anaerobics?

Metronidazole, Clindamycin

Automated MIC Systems Beckman Coulter, Brea, CA 1. Vitek Systems (Vitek 1 and Vitek 2) 2. Microscan WalkAway System 3. BD Phoenix 4. Sensititre

Microscan WalkAway System

Automated MIC Systems Use conventional broth microdilution trays 1. Vitek Systems (Vitek 1 and Vitek 2) 2. Microscan WalkAway System 3. BD Phoenix 4. Sensititre

Microscan WalkAway System

Intermediate

Middle ground of both susceptibility and resistance

What is the function of the geminal dimethyl groups in PenicillinG?

Mimics the substrate that is supposed to fit into the enzyme target -so is the stereochemistry, mimics the d-alanine d-alanine substrate

IE: what valves are most commonly affected in cases involving a single valve?

Mitral Aortic **up to 35% of cases are both valves

IE: what valve is affected with left sided?

Mitral (45%) Aortic (5-35%) Both (<35%)

What coverage does Bactrim provide?

Moderage GNR activity -Enterobacteriaceae (no pseudomonas) Moderage GPC activity -Staph including MRSA -Weak Strep -No enterococcus

Nucleic Acids and Microbial Resistance

Nucleic acid targets- particularly RNA- are the EASIEST to change, and thus the MOST likely to become resistant to the greatest degree -slight modification of enzymes that already exist

IE: most common one?

Native valve endocarditis (NVE)

How do we handle Mycobacteria susceptibility testing?

Negative room required- very delayed responses- special shipping required

Gram Stain --> Negative --> Cocci

Neisseria Meningitidis Neisseria gonorrhoeae Veillonella

Gram - cocci (3)

Neisseria gonorrhoeae and meningitidis Veillonella

TQ** What is an DISADVANTAGE about combination therapy?

Nephrotoxicity Antagonism Addictive toxicities

Disadvantages of combo antibiotic therapy (3)

Nephrotoxicity Antagonism Additive toxicities

ADEs of Vancomycin

Nephrotoxicity Ototoxicity Redman Syndrome

For microtiter plate analyses where do we draw the line?

Next line (first clean spot)

Metronizadole

Nitroimidazole 1st line agent when anaerobes are of concern Agent of choice for C. difficule (mild to moderate) Drug Interactions: Warfarin, Disulfuram reactions w/ alcohol

Can B lactamase inhibitors be used alone?

No

Is Nafcillin orally bioavailable?

No

can you use ceftriaxone in neonates?

No

What is cefepime NOT used for?

No Enterococcus (gram +) No anaerobes

What do the Anti-MRSA agents not cover?

No Gram-Negative Anaerobes

What do Imipenem Meropenem, Doripenem NOT cover?

No MRSA

What does Ampicillin/Sulbactam & Amoxicillin/clavulanate NOT cover?

No Pseudomonas coverage

What does Ceftaroline NOT cover?

No anaerobes No Enterococcus NO Pseudomonas No Acinetobacter

What does Ceftroline NOT cover?

No anaerobes and Enterococcus (-) Psuedomonas or Acintobacter

For Utopiamycin Bacterial Resistance No Bacterial Resistance

No bacterial resistance

What is something to know about monobactam?

No cross activity with beta-lactams

What does Ertapenem NOT cover?

No enterococcus No pseudomonas No Acinetobacter

What does Cefepime not cover?

No enterococcus and No anaerobes (both -)

Gram Stain--> Positive --> Bacilli --> Branching or Filamentous

Nocardia Actinomyces Erysipelothrix

Gram + bacilli branching or filamentous (3)

Nocardia Actinomyces Erysipelothrix

For Utopiamycin: Allergenic Non-allergenic

Non-allergenic

What does an Erythrocyte Sedimentation Rate test reveal?

Non-specific measure of inflammation- inflammation is increased in infection

Penicillin V

Not as acid sensitive but still is... has O between ring and CH2

Ampicillin and Sulbactam

Not as potent as clavulanate IM/IV only Synthetic irreversible B-lactamase inhibitor Can use for acinetobacter

What does C-reactive protein Test reveal?

Not very significant for infection- it is an acute phase reactant and is a marker for inflammation **Increases in inflammation are common during infection

Best place to take temperature

Oral Rectal Axcillary

What is the benefit of 2nd generation penicillins?

Orally bioavailable

Where are beta-lactamases in Gram + organisms?

Outside the peptidoglycan layer

What are the oral penicillinase stable agents? (3)

Oxacillin Cloxacillin Dicloxacillin

What are the isoxazolyl PCNs? (3)

Oxacillin Cloxacillin Dicloxacillin

Isoxazolyl-Penicillins

Oxacillin- hepatitis with prolonged use, neutopenia Cloxacillin Dicloxacillin- B-lactamase inhibitor Acid stable- oral available

B lactamases: Class D?

Oxacillin-hydrolyzing enzymes More common in European/Australian

YycG Histidine Kinase

PAS sensor on outside of membrane No response yet Believe that future resistance will come from this

How do b lactam affect bacteria?

PBP will attack the carboxylic acid on b lactam ring which will inactive PBP so the bug wall will be destabilized

S.pneumoniae resistance: Of the six PBPs from S.pneumoniae, PBP____, PBP____, PBP____ and sometime PBP____ were found to be altered in the resistant clinical isolates

PBP1a, PBP2b, PBP2x, PBP2a

Mutant ______ confers MRSA

PBP2a

S.pneumoniae resistance: Sequencing revealed that mosaic genes encode PBP____, PBP___, and PBP____ in most resistant clinical strains. ______ is the product of recombination events between different alleles within a species or between orthologous genes of related species.

PBP2b, PBP2x, PBP1a Mosaicity

MRSA

PBPs are no longer sensitive to the methicillin

-Mouth -Anaerobes -Enterococci -Strep a. PCN b. Ampicillin/Amoxacillin c. nafcillin d. Unasyn (ampicillin/sulbactam) / Augmentin e. Piperacillin/Tazobactam (Zosyn)

PCN

Streptococcal endocarditis: native valve PCN susceptible (MIC<0.12) dose?

PCN G 12-18 MU/d IV cont or in 4-6 divided doses OR Ceftriaxone 2 g/d IV/IM x 4weeks Plus gentamicin 1 mg/kg IV/IM q8h x 2weeks

Streptococcal endocarditis: native valve PCN intermediate (MIC>0.12 to <5): dose?

PCN G 24 MU/d IV cont or in 4-6 divided doses x 4weeks PLUS gentamicin 3 mg/kg/d IV/IM in the first 2 weeks If prosthetic valve/valvular or prosthetic material x6 weeks

What are the first gen PCN? (7)

PCN G and V Nafcillin Cloxacillin, dicloxacillin, flucloxacillin, oxacillin

Which PCN(s) do(es) not cover H. influence? (based on summary slide)

PCN and Nafcillin

Drug factors (4)

PK & PD considerations Tissue penetration Drug toxicity Cost $

What drug factors should be considered?

PK and PD: -AUC: MIC ratio -Peak: MIC ratio -T>MIC Tissue penetration Drug toxicity Cost (direct and indirect costs)

What is something to know about vancomycin?

PO only covers C. difficile

Disadvantages of an automated system?

Specialists choose the panel and card selection can't ID certain resistant mechanisms Need to know overall or underclass of MIC Majority of results can be outliers

For Utopiamycin: Broad in its actions Specific in its action

Specific in its action

Prevention of IE: Antimicrobial options?

Standard: amoxicillin 2 g PO 30-60 min prior to procedure

IE: most common pathogens? (3)

Staph Strep Enterococci (E.faecalis)

Gram + cocci clusters and coagulase + (1)

Staph aureus

Gram + cocci clusters and coagulase - (5)

Staph epi Staph saprophyticus Staph hominis Staph hemolyticus Staph warneri

What do Penicillinase-resistant agents cover?

Staphylococci DOC for methicillin-susceptible S. aureus (MSRA) Active against streptococci

IE: what are the two pathogens usually responsible for >75% of cases? What is the primary pathogen?

Staphylococci and streptococci S.aureus

Ampicillin/Sulbactam & Amoxicillin/clavulanate covers?

Staphylococci coverage (MSSA, MSSE) Increases anaerobic coverage (including bacteroides) Increases Gram Neg Rod coverage (Haemophilus, Proteus, E. Coli, Klebsiella)

What do penicillinase-R cover?

Staphylococci, Streptococci

What does Ertapenem cover? (4)

Staphylococci, Streptococci, GNR, anaerobes

What do 1st generation cephalosporins cover? (3)

Staphylococci, Streptococci, little GNR coverage (PEK)

What does Ampicillin/Sulbactam and Amoxicillin/Clavulanate cover? (5)

Staphylococci, anaerobic coverage, GNR, Enterococci, Streptococcus

Gram Stain--> Positive --> Cocci --> Clusters --> Coagulase Positive

Staphylococcus aureus

Gram Stain--> Positive --> Cocci --> Clusters --> Coagulase Negative

Staphylococcus epidermidis Staphylococcus saprophyticus Staphylococcus hominis Staphylococcus hemolyticus Staphylococcus warneri

What is Sulfamethoxazole/ Trimethoprim the DOC for?

Stenotrophomonas maltophilia Nocardia Pneumocystis jiroveci (carinii) pneuomonia

What is bactrim the DOC for? (3)

Stenotrophomonas maltophilia, nocardia, Pneumocystis jiiroveci pneumonia

How is Methicillin Beta-lactamase Penicillinase Resistant?

Steric bulk- aromatic ring + ortho substituents on both sides = good protection of aromatic ring -if methoxy groups are in the wrong position (not ortho) or you put the CH2 in-between, it is no longer penicillinase resistant

What are the 4 rare reactions to a beta-lactam that should be treated as a contraindication to therapy with any beta lactam due to lack of safety data?

Steven johnson syndrome toxic epidermal necrosis DRESS allergic interstitial nephritis

What is the coverage of Erythromycin?

Strep (+), Moraxella (-) & atypicals Most MSSA has become resistant Most H. influenza has become resistant **mainly used for GI motility these days

What does Penicillin cover well?

Strep Group A, B, C, G Enterococcus Strep pneumoniae Clostridium perfringens Peptostreptococcus

True/ False: Daptomycin cannot be used for pneumonia

TRUE - inactivated by surfactant in the lungs

beta-lactam cross reactivity mxn

TRUE allergy: CI for any drugs in antibiotic class Cross reactivity with any side chain structure similar to drug allergy R1 side chain structure

ECHO: TTE vs TEE?

TTE: less invasive but harder to visualize valves. Performed in ALL cases of suspected IE TEE: provides most info but most invasive

B lactamase inhibitor: What is version 1.5?

Tazobactam

What are new Anti-MRSA antibiotics?

Tedizolid phosphate (sivextro) Dalbavancin (Dalvance) Oritavancin (Orbactie)

What generations cover Psuedomonas

Third (Ceftiazidime) and 4th

ADEs of Linezolid

Thrombocytopenia Serotonin Syndrome

How are beta-lactams dosed?

Time-dependent bacterICIDAL effects. Killing activity is enhanced marginally if drug concentration exceeds the MIC. Therefore, effective dosing regimens require serum drug concentrations to exceed MIC or 40-50% of dosing interval. Frequent, small doses, continuous infusion, or prolonged infusion T>MIC

Amino glycoside coverage of pseudomonas

Tobramycin > gentamicin

Streptococcal endocarditis: native valve PCN resistant (MIC>0.5): dose?

Treat with regimen for enterococcal endocarditis

What is the pathogen in syphilis?

Treponema pallidum

what is the bacteria name that causes syphallis, and we use penicillin to treat ?

Treponema pallidum

Antimicrobial Susceptibility Testing Special Considerations Special Screening & Confirmatory Tests for Resistant Organisms a. Methicillin-resistant Staphylococcus aureus (MRSA) b. Vancomyocin resistant S. aureus (VRSA) c. B lactamase producing gram negative organisms d. Inducible macrolide-lincosamide streptogamin B resistance (iMLSB) e. extended spectrum B lactamases (ESBLs) f. AmpC type B lactamases g. Metallo B lactamases h. Carbapenemase Resistant Enterobacteriaceae (CRE)

all of above

Cefepime (Maxipime) has a. strep coverage b. MSSA/ MSSE c. no enteroccocus d. all of above

all of above

Cefoxitin, Cefotetan, Cefuroxine (2nd generation) increase in gram negative coverage a. proteus b. e coli c. kelbsiella d. haemophilus e. all of above

all of above

Duration of Therapy for Antimicrobials Considerations include... a. pathogen b. infection type c. response to therapy d. source control? e. all of above

all of above

Establishing the Presence of Infections Polymorphonuclear leukocytes (mature) PMN contain a. neutrophils b. basophils c. eosinophils d. all of above

all of above

Follow Up, monitoring, & Streamlining In our clinical cure, we want to make sure we... a. have a resolution of fever b. normalizing WBC c. physical complaints (SOB, Cough, pain) d. normalization of BP (if in shock) e. improvement if in respiratory status (in pneumonia) f. all of above

all of above

Follow Up, monitoring, & Streamlining Make sure to... a. Assess cultures & susceptibility results b. Streamlining c. Repeat cultures may be necessary d. Clinical cure e. therapeutic drug monitoring f. all of above

all of above

Host Factors Which of following are Host Factors? a. age b. allergy c. organ function d. metabolic abnormalities e. pregnancy status f. cocomittment drug and disease states g. all of above

all of above

Imipenem, meropenem, Doripenem cover... a. MSSA/ MSSE B. Strep c. + /- for Enterococcus d. Good gram - coverage

all of above

Monitor Therapeutic Response Parameters used to diagnose the infection a. WBC & temperature is normalize b. patients complaints have diminished c. radiographic improvement d. antimicrobial serum e. all of above

all of above

What if the patient doesnt improve? think these things through... (she said dont memorize just understand) a. do we have the wrong dose? b. do we have the wrong drug? c. inability to reach PD goal? d. is there poor penetration to site? e. Is there lack of source control? f. is there resistance? g. is it a non bacterial infection like a virus? h. what if there was no infection?

all of above

What is B lactams ADEs? a. allergic reaction b. interstitial nephritis c. seizures d. diarrhea e. thrombocytopenia f. biliary sludging (ceftriazone) g. coagulopathy (cefotetan) h. all of above

all of above

Which of the following are drug factors? TQ** A. Pharmacokinetic and pharmacodynamic considerations b. Tissue penetration c. Drug toxicity d. Cost

all of above

Which of the following are drug factors? TQ** Want to consider the a. AUC: MIC Ratio b. Peak: MIC ratio c. T >MIC d. all of above

all of above

an allergic reaction can cause what manifestations? a. urticarial rash b. hypotension c. bronchospasm d. angioedema e. anaphylactic shock f. all of above

all of above

pharmacist intervention for allergies is important because it reduces the a. less effective b. more toxic b. broader spectrum d. more costly $$ abx e. all of above

all of above

there is special considerations for antimicrobial susceptibility testing for a. fastidious organisms b. anaerobes c. mycobacteria d. all of above.

all of above

Good gram - coverage a. Ceftriaxone b. Cefotaxime c. Ceftazidime

all of them

No Enterococcus or no anaerobes coverage a. Ceftriaxone b. Cefotaxime c. Ceftazidime

all of them

No enteroccus, no anerobes a. Ceftriaxone b. Cefotaxime c. Ceftazidime

all of them

Presence of an infection can be a. leukemyia b. drug fever c. malignancies d. all of above them

all of them

which ones increase in the presence of an inflammatory process? a. Erythrocyte sedimentation rate (ESR) b. C-reactive protein (CRP) c. Cytokines d. Pro-calcitonin e. all of above

all of them

What are the 5 side effects for beta-lactam?

allergic reaction interstitial nephritis seizures diarrhea thrombocytopenia

patients w/ previous allergic reaction may have increased propensity (likelihood) to develop _____

allergy

What is a Hapten?

also known as a allergen a small molecule which combined with a plasma protein can elicit production of antibodies

which antibiotics are concentratin dependent

aminoglycosides

which antibiotics are protein synthesis inhibitors?

aminoglycosides, macrolides, clindamycine, tetracyclines, linezolid, tedizolid, quinupistin/dalfopristin

What are the 2 aminopenicillins?

amoxicillin ampicillin

resistance

bacteria that are resistant to antibiotics

What 3 types does penicillin not cover?

bacteroides gram negative organisms staphylococci

What are the 3 ways to take a temperature? which one is the best? what about the other 2?

best- oral axillary- will be lower temp anal- will be a high temp

what is enzyme inactivation resistance

beta lactamase inhibitors ex) ESBL choose carbapenem

which antibiotics are time dependent

beta lactams

name some hydrophobic antibiotic classes

beta lactams, aminoglycosides, vanco, dapto, poly myxins

which antibiotics work on the cell wall?

beta lactams, monobactams, vanco, dalbavancin, telavancin, and oritavancin

Second Gen penicillin...

better bioavailability (amino group can get through porins) better gram - (still not great)

What are the 5 drugs that cover vancomycin resistant enterococcus (VRE)? which one has limited use ***?

daptomycin linezolid tigecycline eravacycline chloramphenicol****

you should ____patients w/out true allergy

de- label

what are two pathogens susceptible to ESBL and CRE

e. coli and klebsiella pneumonia

What are the 4 lactose fermenter gram negative bacteria?

e.coli Klebsiella pneumoniae proteus sp. enterobacter sp.

what are some common indications for augmentin

ear infection

common used for cefuroxime

ear infections, CAP, and sinus infections

what are some common indications for amoxicillin

ear infections, infective endocarditis prophylaxis, and h pylori

Antimicrobial therapy patients have infection but lack culture documentation a. prophylaxis b. empiric c. definitive

empiric

What do 1st gen cephalosporins have no activity against?

enterococci anaerobic

What do 2nd gen cephalosporins not cover?

enterococcus

What does 3 bugs ertapenem not cover?

enterococcus pseudomonas acinetobacter

What 3 bacteria does Etrapenem have no activity against?

enterococcus pseudomonas aeruginosa acinetobacter baumannii

What are the 4 microbes does penicillin cover?

enterococcus (faecalis > faecium) streptococcus pneumoniae clostridium perfringens peptostreptococcus

Telavancin

jkjkj

What are the most sensitive membranes in humans?

kidneys neurons heart

What does Ceftazidime cover? (3)

less GP coverage, GNR, Pseudomonas

What are the 3 bugs that are not covered by ceftazidime?

less gram positive enterococcus anaerobes

What fluoroquinolones cover strep?

levofloxacin moxifloxacin

daptomycin coverage

like vanco but also covers VRE

linezolid and tedizolid coverage

like vanco but plus VRE

are hydrophilic or lipophilic drugs more likely to have a 1:1 IV to PO ratio?

lipophilic bc better bioavailability

Gram + bacilli small (4)

listeria, propioni, coryne, gardnerella

Name 4 quantitative test

minimum inhibitory conc (MIC) broth microdilution etest automation systems

what is selection pressure resistance?

more resistant bacteria is left to multiply

How is streptococcus pneumoniae resistance different in its mechanism?

mosaic genes encode PBP2b, PBP2x and PBP1a **mosaicity is the product of recombination events between different alleles within a species

Streptococcus pneumoniae resistance

mossaic of class A and class B PBPs -PBP2x: Altered target- most dangerous- can't just push dose Mutates more rapidly that we can hit it with antibiotic

What does aminopenicillins not cover?

most gram negative rods bacteroides staphylococci

What are the 2 bugs that 2nd gen cephalosporins cover?

most strep MSSA

which FQ have IV:PO 1:1

moxi and levo

Fluroquinolones TQ** Which one has anaerobic coverage? a. ciprofloxacin b. moxifloxacin c. levofloxacin

moxifloxacin

What fluoroquinolone has coverage for anaerobic?

moxifloxacin

What is the side effect of daptomycin?

myalgia

B lactams have an excellent _____ profile

safety

What are the ADes of Meropenem and Vaborbactam (Vabormere) ?

seizure CDAD Thrombocytopenia neuromotor impairment

pip tazo coverage

strep enterococci mouth anaerobes h flu MSSA PSEUDOMONAs gut anaerobes most GNR

what does penicillin cover

strep mouth anaerobes enterococci DOC syphillis

What are 2 bugs that are covered by ceftriaxone and cefotaxime?

strep and gram negative

common indications for oral pen VK

strep throat and mild skin infections

common uses for cephalexin

strep throat, MSSA, and skin infections

what does amoxicillin cover

strep, enterococci, mouth anaerobes, H flu, DOC listeria meningitis GP cocci, GP anaerobes, and GN (HNPEK)

What does penicillin cover?

streptococcus and mouth flora

What bacteria does levofloxacin and moxifloxacin have better coverage for over cipro?

streptococcus pneumoniae

which antibiotics are folic acid synthesizers?

sulfonamides, trimethoprim, and dapsone

Local Signs of Presence of Infection You can see signs visually if infection is ____ Symptoms--> refer to the organ system

superficial

whats rifaximin used for

travelers diarrhea, E.COli, IBS, to prevent hepatic encephalopathy

Prophylaxis treatment

treatment given before...to prevent infection from happening

empiric treatment

treatment which begins after samples are collected but before lab results provide definitive results of infection

Nephrotoxicity is higher with higher __________________ vancomycin levels.

trough

Prevention of IE: antimicrobial options Allergy to PCN or ampicillin: type I? Type II?

type I: clindamycin 600 mg PO, Azithromycin 500 mg, clarithromycin 500 mg Type II: cephalexin 2 g


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