IS8e1
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
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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
