Antibiotics to
Cefoxitin
2nd generation cephalosporin Treatment for: -same things as cefuroxine-Respiratory tract infections (S. pneumoniae; H. influenzae) - covers all H. spp unlike amoxicillin -V important in pediatrics- because it treats most important pathogens (S. aureus, GAS, GBS, S. pneumoniae) (and E. coli) -Important part is that is also treats B. fragilis (i.e. effects anaerobes) -Good for abdominal infections, UTIs, pelvic infections, etc -Also can be used for diabetic foot ulcers with poop flora
Ceftriaxone
3rd generation cephalosporin Treatment for: -Gram-negatives (less so the positives like S. aureus/GAS) -Gonorrhea -outpatient antibiotics (because it has a very long 1/2 life) -Also important for hospital acquired infections
Ceftazidime
3rd generation cephalosporin Treatment for: -important because it covers pseudomonas -also treats E. coli and H. infulenzae
Bacitracin
a cyclic polypeptide antibiotic which inhibits cell wall synthesis -It is active against Staph and strep and also clostridium -not active against gram-negative bacilli -it is used locally for the treatment of furuncles, carbuncles and abscesses. Local side effects are rare and include sensitivity.
Imipenem (meropenem)
Carbapenems- broad spectrum antibiotics -use this when you don't know what's going on -Multi pathogen infections -covers most of the pathogens
Broth Dilution
Each well doubles in dilution of the antibiotic. the stuff at the bottom is the bacteria and when this disappears we can it our minimum inhibitory concentration
Empiric vs. directed anti-microbial therapy
Empiric- won't have the culture. Treat based on knowledge of likely pathogens. Ex. cystitis- you dont need to do culture to see if its E. coli, empiric treat based on likely pathogens. In out-patient setting everything is empiric Directed- on day 2-4. In hospital you will culture everything that is relevant to the infection. On day 2-4 you get results back and move from empiric treatment that is broad and de-escalate and give whatever the bug is sensitive to. In hospital we start empiric and 50% of the time we have culture and de-escalate
Prophylaxis for staph infections
Good aseptic surgery techniques, having the patient shower/scrub down the night before or preferably the morning before. -Also give 1gram cafazolin 1hr to 30 minutes prior to surgery
Diffusion
each disc has an antibiotic that is put on a plate of bacteria -wider the zone of inhibition the more susceptible the bacteria is -the diameter is directly proportional to the susceptibility
How to manage TSS
Take out the packing and clean the wound, start IV Vanco and probably an IV immunoglobulin -Manage vitals symptomatically- may need fluids, respiration etc.
Contaminant or not
-Two cultures taken, Temp 37.9, central line- two cultures positive for S. epidermidis- likely real- multiple cultures positive -Two cultures taken, vague symptoms, POD 5- one positive for corynebacterium- contaminant- only one culture positive, common contaminant -Three cultures taken, weight loss- one culture positive for S. aureus- likely real- virulent pathogen
Sicker/more immunocompromised patients
-A greater number of critically ill patients in ICU's, greater numbers of critically ill patients in ICUs, greater numbers of immunocompromised patients and greater numbers of patients undergoing invasive instrumentation or possessing peripheral or central intravenous lines and urinary catheters. -These patients frequently receive multiple broad-spectrum antibiotics which facilitates colonization and infection with resistant bacteria
How do you treat a skin soft tissue infection
-Probably start with IV Vanco to cover your staph and strep basis -when you figure out what the pathogen is, if it isnt resistant we can go down to cloxicillin (Most staph infections are resistant to amoxicillin because they produce ß-lactamases so thats why we use clox)
Specimen selection
-Right specimen- without the correct specimen, test result could be inaccurate or mis-interpreted -Proper collection and transport- every specimen type usually requires specific collection devices, sufficient volume, and have specific transport and storage requirements. Failure to follow may result is false- negative results -Right test- ordering the wrong test when another test is more suited is detrimental to patient care
Serological detection of pathogens
-Serological detection depends on the demonstration of targeted antibodies to a specific pathogen antigen -Several classes of antibody are produced by humans- IgG and IgM are most relevant to diagnostic microbiology
Fluoroquinolones
(ciprofloxin, norfloxacin) -very broad spectrum with activity against gram-positives and gram-negatives. -active against mycobacterium, mycoplasma and chlamydophila -MAIN use is for treatment of serious gram-negative bacilli infections Adverse= GI upset and CNS.
History of antibiotic use
-Alexander Fleming discovered penicillin in 1928 -Changes to antibiotics lead to changes in bacteria to become resistant and its been a race ever since -By the end of the 1980's, office-based physicians in the US were prescribing an estimated 110 million courses of antibiotics per year. (28% increase over the decade) -Many major pharmaceutical companies had either dismantled completely or dramatically downsized their antibiotic development programs. which resulted in few new antibiotics in the pipeline
Developing countries
-Almost 80% of the worlds population live in Africa, the Middle East, Latin America and Asia -Although these countries consume only 20% of the worlds supply of antibiotics, they have very high antibiotic resistance rates compared to other parts of the world -Due to combination of a heavy burden of bacterial infectious diseases, huge populations without even the rudiments of primary health care, rapid spread through crowding, poor sanitation and sexual contact -OTC antibiotics, overcrowding of hospitals, lack of infection control policies and self-medication are present and impact resistance -the mobility of the world population facilitates the spread of antibiotic resistant bacteria around the globe
Selective bacterial colonization
-Almost all patients who acquire systemic VRE infection are initially colonized with VRE in the large bowel -Selective bacterial colonization works by restoring a patients normal bowel microbiota with the administration of "normal bowel microbes" (probiotics or fecal microbiota transplantation) -This microbiota competes with the antibiotic-resistant bacteria in the resistant microbiota to lower their numbers and also reduces the likelihood of antibiotic-resistant infection or transmission to other patients
Antibiotic use/abuse
-Antibiotic resistance has been a problem in tertiary care hospitals for many years -The primary reason for the development of antibiotic resistance -Antibiotic resistance development is high in areas of the hospital with highest antibiotic usage (ICU) -Broad spectrum oral antibiotics are now frequently used in the community, which leads to maintaining resistance strains and therefore a greater chance of community- acquired infection caused by resistant organisms -~40-60% of antibiotics are used inappropriately or unnecessarily -
Principle of antigen detection
-Antigen detection can be used to identify organisms directly from patient samples -Principle is a specific antibody that binds to a specific antigen of a known pathogen and creates a visible reaction-some kits can be used in office setting, others usually in labs -Caution with interpretation of results- cross reactivity, sensitivity
Antigen detection
-Antigen detection- principle is to use a stationary antibody that binds a specific antigen (protein) related to an infection and produces a visible reaction -Theoretically can be used for almost any pathogen. More commonly used for streptococcus pyogenes, legionella, streptococcus pneumoniae, multiple viruses, clostridioides difficile -Most important limitations are sensitivity and cross reactivity
General rules for culture
-Bacteria and fungi- get a fresh specimen that represent the infected site. Swabs are the least sensitive but easiest and in general only suitable for bacterial culture -Heed specific transport and storage requirements -Specify if atypical organisms are expected -Aspirates and biopsies are best for unusual cases or definitive diagnosis. Histology can help too -Viruses- collect early in illness. Obtain specimen according to suspected disease, give history, transport in Virus Transport Medium (VTM). Acquire best specimen for disease -Generally speaking, culture is required for susceptibility testing
Continuous bacteraemia
-Bacteria are not cleared from the circulation and culture will demonstrate them at all times -Usually related to disease, sometimes to organism- especially endocarditis
Antibiotic cycling
-Based on the premise that intense use of one class of antibiotics eventually leads to resistance -By changing the major antibiotic class used, perhaps on a trimonthly basis, less intense selective pressure for that class of antibiotics may result in less resistance
Blood cultures
-Blood cultures are one of the most critical specimens in microbiology -Accurate collection and interpretation is critical to patient management
What happens in the lab
-Blood is inoculated into special culture bottles containing enriched media at the bedside -The bottles are incubated into an automated incubator/culture reader/computer -Specimens are incubated at 37 degrees C for a maximum of 5 days -An LED light reads each bottle every five minutes and detects growth "real time" -The computer alerts the user as soon as the culture is positive
Mechanisms of antibiotic resistance
-Can be intrinsic (DNA mutation in a target site or upregulation of an efflux pump) or extrinsic (acquire exogenous DNA) -Mutation in DNA is a common way to develop antibiotic resistance. Acquisition of foreign DNA (plasmid or chromosomal) is also a common way to develop resistance -The genes conferring antibiotic resistance may also be packaged in packets of DNA called transposons allowing the transfer of resistance from one organism to another or from one DNA site to the other -Therefore, acquisition of plasmids or transposons may result in the development of antibiotic resistance by previously susceptible bacteria
Industrialized vs developing countries antibiotics
-Developing have only ~20% of world supply of antibiotics, yet they have the highest rates of antibiotic resistance -Resistance to older traditional agents like choramphenicol, ampicillin and sulfonamides. (Ex. Typhoid fever and shigella causing dysentery are commonly resistant to the normal over the counter meds. A STI Chancroid is also resistant. Therefore, fluoroquinolones and third gen cephalosporins have replaced these agents -Industrialized- report antibiotic resistance to newer, more potent antibiotics which are widely abused. In addition, not only are industrialized countries able to purchase the more expensive agents, they tend to overuse these agents over the older antibiotics again contributing to the emergency of antibiotic resistance
Susceptibility testing
-Susceptibility testing of bacteria is done using one or several methods: broth dilution, agar dilution, diffusion, or rapid enzymatic methods -Provides information on the antimicrobials that effectively inhibit the growth of the organism -Testing is very specific to organism and drug and interpretation is not always possible -Interpretation (S,R,I) relates to many factors
Bacteraemia
-The presence of viable bacteria in the blood
Extended Spectrum ß-Lactamase (ESBL) Producing E. coli and Klebsiella Spp.
-ESBL producing E. coli occurs with a prevalence of 5-30%. These strains are found both in the community and the hospital and is highest in the ICU -ESBL producing Klebsiella spp occurs with a prevalence of 5-20% -ESBLs are resistant to 3rd gen cephalosporin such as cefotaxime and ceftriaxone and are frequently concomitantly resistant to fluroquinolones, sulfonamides and aminoglycosides like gentamicin -ESBL may cause community acquired urinary infections, respiratory infections, bacteremias and wound infections -Currently, carbapenem resistant E.coli and Klebsiella are not common in Canada but expected to become more so
Community acquired infections
-Emergence of several antibiotic resistant organisms include: -CA-MRSA -multi-drug resistant ESBL producing E.coli -multi drug resistant Neisseria gonorrhoeae -ß-lactamase producing Haemophilus influenzae -Penicillin-resistant and multi-drug resistant S. pneumoniae Which represent a significant and growing threat -These changes have shifted therapy from traditional agents (penicillin or ampicillin) to more portent ß-lactamase stable antibiotics such as ampicillin/clavulanate, cefuroxime, cefixime or ceftriaxone
Interpretation of serology
-Enormous variation in antibody response exists, but generally presence of IgM or rising IgG level to a pathogen support a recent infection and stable IgG levels implies a remote infection -Paired sera for IgG with a ≥4 fold increase in titre is a more definitive indicator of acute infection
Antibiotic use in animals
-Food animals and some companion animals receive many times more antibiotics (4x in Can/US) than humans -Antibiotics are used to prevent or treat infections -Their main use is to facilitate faster growth of cows, hogs, poultry, and fish from each kilogram of feed. Resistant organisms and antibiotic resistance genes emerge in animals as they do in humans and have been shown to spread to humans
Pneumocystis carini
-Fungi/pathogen that causes pneumonia in people with HIV
Intermittent bacteraemia causes
-GU tract (25%) -Biliary tract (5%) -Skin/soft tissue (5%) -Abscess (10%) -Lungs and resp tract (20%) -Unknown or primary (25%)
OTC antibiotics/self medication
-In many countries, regulation of pharmaceuticals is poor or non-existent -Some patients prescribed oral antibiotics commonly do not finish the recommended course of therapy often stopping after they feel better and storing the remainder in the medicine cabinet -This leads to self medication, for inappropriate infections using inappropriate doses and duration of therapy often with outdated antibiotics -This situation could lead to selection of resistant bacteria and subsequent transfers of these bacteria to others
Major reasons for why antibiotic resistance has occurred
-Increased antibiotic use/abuse -More immunocompromised patients -OTC antibiotics/self-medication -Poor patient adherences -inadequate infection control -travel facilitating resistance spread -Industry advertising/promoting -developing countries -antibiotic use in food and companion animals
Fusidic Acid
-Inhibits protein synthesis by interfering with elongation factor G -Used to treat Staphylococcal and/or Streptococcal skin Infections -Local side effects include contact sensitivity.
Industry advertising/promoting
-Intense pressure from the pharmaceutical companies through detailing, promoting and advertising new broader spectrum antibiotics leads to increased antibiotic use -We are using more broad spectrum agents in hospital and community
Muciprocin
-It inhibits protein synthesis by binding to bacterial isoleucyl -tRNA synthetase -It is active against Staphylococci (including MRSA) and Streptococci (except Enterococcus -It is used for impetigo, folliculitis and other skin infections caused by Staphylococci and/or Streptococci. It is used to eliminate nasal carriage of MRSA. -Local side effects include dermatitis and rashes.
How to assess antimicrobial efficacy clinically and using lab
-Labs do gram stains and culture. If you haven't sterilized the blood or urine in 2-3 days, then something is wrong. It can take a little more time for the patient to get better -Is fever, shortness of breath, energy, etc getting better. -By day 2-4 you should be better, if not then something is wrong- so in clinic we are looking for signs and symptoms
Microscopy
-Light microscopy- depends on the use of stains that preferentially bind to structures. Some are simple wet preps. Gram stain done on almost all specimens -Fluorescent microscopy- fluorescent stain or antibody preferentially binds to organism -Electron microscopy- viruses -Darkfield- rarely done. Historically to identify syphilis
Proteomic identification
-MALDI-TOF is a revolution in microbiology. Represents the only way routine laboratories will perform identification in the next 10-15 years -It is matrix-assisted laser desorption/ionization- time of flight mass spec -uses mass spec to rapidly analyze the proteome of intact bacteria to provide definitive identification (~5min)
Methicillin-resistant Staphylococcus aureus (MRSA)
-MRSA occurs with a prevalence of 10-50%, mostly in hospitals and nursing homes -Altered PBP which is coded by the mecA gene- can be detected with PCR -CA-MRSA causing severe skin and soft tissue infections in healthy subjects as well as invasive infections such as necrotizing pneumonia have rapidly spread across the US and Canada -There are limited treatments for systemic infections caused by these organisms including vancomycin, linezolid, daptomycin, ceftobiprole, telavancin and tigecycline -Nasal carriers of MRSA can be treated with rifampin or topical mupirocin -Rare reports of VRSA are concerning- the result of a VRE strain transferring a transposon to MRSA creating VRSA- this theoretically could be treated with linezolid, ceftobiprole or tigecycline
Mycobacterium
-Main cause of tuberculosis
Biochemical identification
-Manual, semi-automated and fully automated methods exist -Fermentation of sugars, metabolism of AA, metabolism of other molecules are common
Molecular methods in bacteriology
-Molecular detection can be used to identify bacterial pathogens from patient samples -Assay generally have high sensitivity and specificity -Caution in interpreting results: cross reactivity, non-viability, colonization vs infection, sample contamination
Number of sites
-More sites helps enhance the specificity of the blood culture for true bacteremia -Helps decide if a positive culture consists of contamination or bacteremia -May help diagnose infections caused by organisms considered contaminants -May help determine if an infection is from an indwelling catheter- culture drawn from catheter positive before peripheral site -At least 2 different sites must be done for cultures to be useful
Bacterial culture
-Most bacteriology is done by culture -Specimens are inoculated to media supporting the growth of bacteria -Incubation typically takes 24-48 hours -Identification usually occurs after incubation is complete, but may take additional 24 hours -Susceptibility testing usually takes 24 hours after incubation is complete
Culture
-Most organisms can be cultured -Bacteria- most require nutrients, humidity, and heat. Some need special media or atmosphere. Almost all grow within 48-72 hrs -Fungi- may not require increased heat, require nutrients and humidity. Most require 7-20 days to grow (except yeasts). Most yeast grows very quickly on routine media -Viruses and chlamydia- require special cell cultures. 3-20 days for growth depending on the virus. Only done is specialized labs -Mycobacteria- most require 2-12 weeks to grow in special conditions
Penicillin-Resistant Streptococcus Pneumoniae
-Occurs in ~5-10% of blood and CSF isolates and in ~15-20% of non-sterile sites -Penicillin-resistance is mediated by alterations in affinity for penicillin-binding proteins (PBP) for ß-lactam antibiotics -Chromosomal resistance has occurred through the creation of mosaic PBPs through recombinational events of viridans streptococci and S. pneumoniae -The major concern with PRSPs is the fact that they are frequently co-resistant to cephalosporins, macrolides, tetracyclines, sulfonamides and even fluoroquinolone which limits treatment options -Treatment requires a third gen cephalosporin (ceftriaxone) with vanco (for ear infection/ minor infections possibly high dose amoxicillin or 2nd gen cephalosporin)
Transient bacteremia
-Occurs transiently when tiny abrasions or cuts occur on contaminated skin or mucous membranes -Usually no consequence to normal healthy hosts and usually asymptomatic -Can seed joints, bones, damaged heart valves, kidneys, damaged vessels, skin... and lead to symptoms and more serious bacteremia -Generally not detected using blood cultures
Identification of bacteria
-Once bacteria are growing, they may require definitive identification- important for specific disease associations and empiric antibiotic therapy -Identification traditionally done using stains and biochemical tests- surrogate for microbial metabolism
Methods in common use
-PCR -RT-PCR -real time PCR -NASBA (TMA and others) -Sequencing -Others
Poor adherence
-Patients might take an antibiotic only until resolution of their symptoms instead of completing the prescribed course -May not only lead to relapse or complications, but also contribute to the selection of antibiotic-resistant strains -Patients prefer to take antibiotics once daily or twice daily whereas patient adherence to therapy declines markedly with TID or QID administration
Inadequate infection control
-Patients who become colonized with antibiotic resistant bacteria are transferred to medical or surgical wards where these resistant strains might easily spread to other patients. This spread is most commonly facilitated by the hands of health care workers or from fomites used for patient care. -These antibiotic-resistant bacteria may produce infection while patients are in hospital or simply remain colonized but uninfected until discharge -If discharged, patients may be transferred to a community hospital or discharged home to finish convalescing and resistant organisms could then transfer to other patients, family or friends -Handwashing by healthcare personnel is most important to prevent the movement of antibiotic resistant pathogens
Serology limitations
-Persistence of IgM can be protracted for some infections -IgM production may be blunted or lag in acute infection -Single IgG provides no information on acuity -Re-infections or reactivations can occur even if IgG is present -Cross reactivity between closely related pathogens is common, especially in early illness -IgM cross-reactivity is common -Auto-immune disorders, pregnancy and immunosuppressed states complicate interpretation of serology
Nucleic acid amplification tests for pathogens
-Principle is the detection of pathogen nucleic acids by in-vitro amplification of RNA and DNA -Very versatile: nearly all pathogens can be detected and can be applied to most specimen types -Generally very sensitive and specific
Vancomycin- resistant enterococci
-VRE colonization is reported throughout Canada -Outbreaks of infections have occurred in most major Canadian centres -Many genes responsible for glycopeptide resistance (Van-A, Van-B, Van-D, Van-E, Van-F, Van-G). These genes are found on transposons or plasmids -Vancomycin resistance is mediated by transposon conferring resistance to both vanco and tecioplanin -Could also be mediated by a plasmid/chromosomal determinant that confers vancomycin resistance only -VRE are commonly resistant to aminoglycosides, penicillins, and fluoroquinolones leaving these superbugs virtually untreatable. -VRE can only be treated with linezolid, tigecycline or daptomycin
Collection procedures
-Wear gloves -Disinfect top of culture bottles with chlorhexidine/EtOH or EtOH then LET DRY -Wash vein site with chlorhexidine/EtOH in back and forth movement over a 4cm x 4cm area. Let dry and repeat -Puncture vein and collect specimens. Do not palpate vein after disinfection unless you have sterile gloves
Nitrofurantoin
-bacteriostatic/bactericidal versus gram-positive and gram-negative organisms. -used orally as first-line treatment of acute uncomplicated cystitis because of its excellent activity versus E. coli including resistant strains -not used for systemic infections (like pyelonephritis) because of poor bioavailability -should not be used in patients with creatinine clearance <30ml/min because of reduced efficacy and increased toxicity
Gramicidin
-binds to cell membranes and causes leakage of ions leading to cell death -It is active against staph and strep, but gram-neg. bacilli are resistant -used for similar infections as bacitracin and demonstrates virtually no toxicity when used topically -Side effects when used locally are limited to contact dermatitis
Blood culture contamination
-coagulase neg. strep, bacillus, diphtheroids, micrococcus, viridans group strep, cutibacterium are all usually contaminants -S. aureus, ß-hemolytic strep, E.coli and like, candida, S. pneumoniae, Pseudomonas, Haemophilus, Neisseria, Listeria are ALWAYS considered pathogens -If only one of multiple cultures grows an organism that is a typical contaminant, it probably is -If multiple cultures grow the same contaminant, it probably isnt
Criteria for a diagnosis of toxic shock syndrome
-fever -low bp -rash 3 or more of involvement from: -GI -Muscular -mucus membranes -kidney -liver -CNS -blood cell hemolysis
Fosfomycin
-good for both gram positive and gram negatives -it is used orally as first line treatment for acute uncomplicated cystitis (excellent activity vs. E. coli) Safely used in any trimester of pregnancy
Gram stain
-gram stain is the most important stain used in bacteriology -provides rapid information about bacteria associated with an infectious process -Provides basic information about inflammation (presence of neutrophils) and surface contamination (presence of epithelial cells) -Understanding the gram stain result requires clinical and microbiological correlation
Main disadvantages of Nucleic acid amplification tests
-inability to differentiate viability, lack of organism recovery, lack of susceptibility testing, cannot discriminate chronic infection or colonization from acute infection, potential for cross contamination, need for expertise and cost
Rifampin
-inhibition of DNA-dependent RNA-polymerase which prevents transcription. -very active against mycobacterium, legionella, and chlamydiophila -resistance develops within a matter of days if the agent is used alone
Polymyxins
-interfere with the structure and function of the outer and cytoplasmic (inner) membranes. -work for gram-negative bacilli, with gram-positive bacteria being resistant -Topically, they are rarely used alone and are usually combined with bacitracin or gramicidin or neomycin which possess activity against gram-positive bacteria -Local side effects are rare and include hypersensitivity (rashes, pruritis, drug fever
Bacteriological diagnosis
-microscopy -routine culture and identification -susceptibility testing -Antigen (and toxin) detection -Nucleic acid amplification -serology -special consideration- blood cultures
Intermittent bacteremia
-occurs when bacteremia results from an infected focus- most bacteremias fall into these categories -Symptoms of bacteremia (septicemia) often occur after bacteremic phase is over- fever, rigors, chills, malaise, apprehension, hypotension -Ideal time to culture is just before fever- impossible in principle, but should be very soon after onset
Metronidazole
-very active against anaerobes -used to treat mild to moderate Clostridioides difficile infections Side effects: -causes intense nausea and vomiting
82 yo female in nursing home. Often incontinent. Otherwise well (no fever, confusion, dysuria, frequency or urgency) the nurses noted that her urine smells funny past 2 days and you order urine culture. It grows E. coli and is susceptible to fluoroquinolone or ciprofloxacin 1. Does this patient have a UTI 2. Should she be treated with ciprofloxacin -She was prescribed ciprofloxacin. after this her urine stopped smelling funny and we repeated culture to make sure no more E.coli. It grew candida albicans 3. does she have a UTI 4. Would you treat the fungus
1. No signs or symptoms so she does not have UTI. we dont want to treat ASB unless pregnant or someone going into prostate surgery and worried about bacteraemia 2. She should be given nothing and talk to the nurse because smelling urine isn't bad. Only treat if she had symptoms 3. Never did 4. We should not treat the yeast because she is asymptomatic. If you treat fungus, you kill normal flora and then you get multi-drug resistant bugs (BAD)
75 yo male. 2 day purulent cough, chest pain while breathing, fatigue, mild fever. He is 40-pack year smoker with chronic bronchitis and diagnosed with community acquired pneumonia. Sputum and blood cultures are collected and he is empirically started on IV levofloxacin. After 24 hr stay, he is discharged with oral clarithromycin 1. How was empiric therapy chosen 2. How to assess antimicrobial efficacy
1. Classic signs and symptoms of pneumonia. We like to do a X-ray to rule out bronchitis. Localized infection to the lungs so we use the guidelines. Levo is a strong drug for Resp infections, then we use the first line treatment when we know and send him home 2. want to make sure fever is going away and stuff. The moment he is stabilized for 24 hours and can take fluids we can send him, which should be within 2-3 days. Sputum should be negative and WBC going down
5 rules for blood culture collection
1. Must be clean 2. Must have a right volume (not too much or too little) 3. Must be from 2 or more DIFFERENT sites 4. Must be taken at the right time 5. Must be well labelled (patient, site, collector and clinical information)
3 mechanisms of antibiotic resistance
1. Production of antibiotic modifying/inactivating enzymes 2. Altered target 3. Decreased accumulation -The most common cause of ß-lactam resistance occurs due to enzymatic degradation of the antibiotic -Decreased affinity for the site of action of an antibiotic depends on the specific antibiotic -Alteration of penicillin-binding proteins (PBP) occurs through change in the structure of the target protein or through production of a new PBP -For antibiotics that act within bacterial cells such as erythromycin, chloramphenicol, clindamycin, or aminoglycosides, alteration of the target ribosomal subunit can cause resistance to the effects of the antibiotics
ß-lactam hypersensitivity reactions
1. Type 1- Immediate (anaphylaxis)- occurs in 1 in 10,000-15,000 (mortality 10-25%) within minutes with parenteral and within 2 hours with oral beta-lactams. Manifested by severe broncho-constriction (wheezing), laryngeal edema ± hypotension. Treatment is epinephrine with steroids and supportive care 2. Type 2- (accelerated)- occurs in 1% within 1-72 hours and is manifested by urticaria (hives), fever and rarely, wheezing and hypotension. Mortality is rare -Penicillins, Cephalosporins, and Carbapenems are contra-indicated in patients with Type 1 and 2 hypersensitivity (with pulmonary or cardiovascular component) 3. Type 3 (delayed)- occurs in 1-10% after 72 hours and s manifested by rashes, fevers, serum sickness, etc. Patients can receive a ß-lactam after having a type 3 reaction
25 yo. female with 1 day fever, chills, nausea, vomiting, flank pain, urinary urgency, and frequency. Diagnosed with acute pyelonephritis. We take urine and blood cultures and she is empirically started on IV ceftriaxone and admitted to hospital 1. Why do we take both blood and urine 2. How was empiric antimicrobial therapy chosen She is found to have E.coli in urine, which is resistant to amoxicillin. 3. how do you decide what pathogen directed therapy you put the patient on 4. how to assess antimicrobial efficacy
1. Urine looks for bacteria in the urine and blood looks for bacteria in the blood. Urine will be positive most of the time and blood less so, but it is still important to check and can give you more confidence in your diagnosis 2. We chose ceftriaxone because it has good activity against E. coli which is what we think it is. And we give a loading dose because it makes sure we get to the therapeutic dose faster (but doesn't mean we reach steady state faster). We want aggressive therapy in the first 24 hours 3. We want to focus on something narrowly for E. coli. Ceftriaxone is IV only, while the others are oral 4. Looking at signs and symptoms, to make sure they go away (should by day 2 or 3), Lab does cultures and it should be clear and blood leukocytes should go down. When person has no fever, feeling better, can eat and have oral fluids they can go home
1.5 yo with fever, irritability, not eating or sleeping, and favoring right ear. Right acute otitis media, probably caused by S. pneumoniae, H. influenzae, or virus was diagnosed. 1. Does he require antibiotics 2. If we chose antibiotics how is the drug, route, dose, etc. selected 3. 1 day later, brought back-what factors may contribute to unfavorable clinical response
1. We are using empiric antibiotics (not gonna stick a needle in buddies ear) and assume he needs antibiotics. He has a fever and is symptomatic, and we treat kids who are symptomatic 2. we want something that will cover the possible bacterias (amoxicillin good choice) and we want a relatively short does ~3-7 days. We give him amox 3/day for 7 days 3. Could be a viral infection not bacterial. The bacteria could be amox. resistant. Could be a different bacteria we hadn't covered with our drug. There might be non-compliance- child not taking the med 3/day. Also need to wait 2-3 days for effect, 1 day not long enough. If worse on day 2-3 that is bad and should come back, but 1 day isnt enough time
Cefazolin (IV)/ Cephalexin (oral)
1st generation cephalosporin Treatment for: -Prophylaxis to prevent post surgical infections (cefazolin) -E. coli (UTI) -Skin/soft tissue infections (S. aureus)
Cefuroxime
2nd generation cephalosporin Treatment for: -Respiratory tract infections (S. pneumoniae; H. influenzae) - covers all H. spp unlike amoxicillin -V important in pediatrics- because it treats most important pathogens (S. aureus, GAS, GBS, S. pneumoniae) (also treats E. coli)
Adequate volume for adults and children
Adults -The best way to increase sensitivity- bacteremias are usually low grade. -Each culture should be 10-20mL of blood. Two cultures should be taken from each patient -Anything less than 10mL is bad practice Children -Volume for kids depends on weight -Pediatric bottles should never be used for kids over 27 kg - use adult bottles and volume -No more than 4 mL per pediatric bottle
Gentamicin
Covers gram-negatives (and adding vanco covers gram-positives) -If we add ampicillin this is a good treatment for pyelonephritis Side effects: -causes nephrotoxicity and autotoxicity (can be high frequency hearing loss or vestibulocochlear loss)
B. fragilis
Found in everyone's colon -Most abundant organism in poop -obligate anaerobe -if it gets into the abdomen, it causes problems and abscesses -Also often found in diabetic foot ulcers
Enterococcus/ E. coli
Found in the intestine -Cause abdominal infections or UTIs
GAS/S. Pneumoniae
Found in the throat and skin -#1 bacterial cause of upper respiratory infections -#2 cause of skin/soft tissue infections -can also cause TSS and necrotizing fascitis
Pseudomonas
Found where there is water. -Commonly found during dialysis, in ICU, or with ophthalmology. Often found with burn victims -Most feared cause of hospital acquired infections because it is v resistant to antibiotics and difficult to treat
How to combat antibiotic resistance
Involves a multi dimensional plan 1. Prudent antibiotic use (antibiotic stewardship) 2. Practitioner education 3. Enforcing infection control practices 4. Development of new antibiotics 5. Active surveillance programs 6. Treatment guidelines 7. Patient supervision/adherence 8. Antibiotic cycling 9. Selective bacterial colonization 10. Bacterial vaccines 11. Computer technology 12. reassuring the public
Clari/ Azithromycin
Macrolides Treatment for: -GAS/Pharyngitis for those allergic to amoxicillin -covers legionella, chlamydophila, mycoplasma as well which makes it a good option for pneumonia- therefore it is a first line treatment for pneumonia for those who are not resistant to bacteria (Erythromycin was another macrolide that had been used but caused too much stomach upset so not used as much anymore)
Where do you find S.aureus
Mostly on the skin, nares, and throat -It is the #1 cause of skin/soft tissue infections -Can also cause TSS, SSSS, and food poisoning
Nosocomial acquired infections
Nosocomial- majority of the antibiotic resistant organisms have occurred within hospitals and long term care facilities. Organisms of concern include: -Methicillin-resistant S. aureus (MRSA) -Vancomycin resistant enterococci (VRE) -Resistant gram-negative bacilli (ESBL, CRE) In some institutions in North America and world-wide the prevalence of MRSA is 50% or higher. Also, mechanism of resistance from VRE has been transferred to S. aureus resulting an untreatable VRSA (only a limited number of cases of VRSA has been reported)
Pyelo, otitis media and skin/soft tissue duration of therapy
Pyelo- 5 days Otitis media- 3-7 days Skin/soft tissue- 7 days -Goal is to try and shorten the days so you can kill pathogen fast and leave good bacteria alone. The shorter the better. Longer in hospitals
Specimen and test: Bacteraemia
Specimen- Blood Test- aerobic and anaerobic bacterial culture
Specimen and test: Meningitis (viral)
Specimen- CSF Test- NAAT, viral culture
Specimen and test: Meningitis (bacterial)
Specimen- CSF Test- bacterial culture
Specimen and test: UTI
Specimen- Midstream urine, catheter urine Test- Quantitative culture
Specimen and test: Complicated or sterile site (CSF) bacterial infection
Specimen- aspirate or tissue Test- aerobic and anaerobic bacterial culture
Specimen and test: Cervicitis, urethritis
Specimen- cervical swab, urethral swab, or urine Test- Gonorrhea and chlamydia NAAT
Specimen and test: Bacterial conjunctivitis
Specimen- conjunctival swab Test- bacterial culture
Specimen and test: Viral URTI
Specimen- nasopharyngeal swab or aspirate Test- NAAT or culture
Specimen and test: Systemic viral infection
Specimen- serum, blood Test- serology, NAAT
Specimen and test: superficial fungal infection
Specimen- skin scrapings, hair, nails Test- fungal culture
Specimen and test: Bacterial pneumonia
Specimen- sputum, endotracheal specimen, bronchial washings Test- bacterial culture
Specimen and test: Bacterial gastroenteritis/colitis
Specimen- stool Test- culture and C. difficile toxin
Specimen and test: Wound infection
Specimen- swab of wound bed, aspirate or tissue Test- aerobic bacterial culture
Specimen and test: Bacterial pharyngitis
Specimen- throat swab Test- culture (S. pyogenes) or antigen detection
Specimen and test: Bacterial vaginosis or vaginitis
Specimen- vaginal swab Test- gram stain for BV and yeast, trichomonas antigen
Legionella, chlamydophila, mycoplasma
These are atypical pathogens that we can't grow in the lab -Important causes of respiratory infections (pneumonias) -Legionella- causes pneumonia in older people -Mycoplasma- causes pneumonia in teens/Y.A. -Chlamydophila- can also cause pneumonia. #1 cause of STIs in the Western World
Vancomycin (IV)
Treatment for MRSA -Oral vancomycin is used for C. diff infections Side effects: -Hearing loss (autotoxicity) -Kidney toxicity (nephrotoxicity)
Amoxicillin/Ampicillin
Treatment for: -#1 go to for GAS/Pharyngitis -E. coli + enterococci (only if the patient is pregnant! used to treat asymptomatic bacteriuria, cystitis, and pyelonephritis) -H. influenzae and S. pneumoniae - treatment for respiratory tract infections (otitis, bronchitis etc)
Cloramphenicol
Treatment for: -B. fragilis (abscesses) mainly in children -Multi drug resistant pathogens -typhoid -Treats our atypical causes of pneumonia Side effects: -Causes aplastic anemia (effects WBC, platelets, etc)
Penicillin
Treatment for: -GAS/ Pharyngitis -Dental infections -Syphilis (can also be used for enterococcus)
Amoxicillin/clavulanate
Treatment for: -GAS/Pharyngitis -S. pneumoniae; H. influenae -E. coli; enterococcus- V. good for UTIs -treats B. fragilis- can be used for diabetic foot ulcers or abdominal infections -The #1 choice for BITE WOUNDS (also treats S. aureus)
Doxycycline
Treatment for: -Orally used for MRSA skin infections -respiratory infections- covers atypical pathogens of pneumonia as well as H. influenzae and GAS/SPN -treatment for acne -and for chlamydia Side effects: -Takes 4-6 weeks to work, and it will get worse before it gets better -Tetracycline destroys abdominal flora so that yeast overgrows in the colon and gets to vagina or causes oral thrush -Interacts with oral contraceptives causing break through pregnancies, and they are teratogens- so bad in pregnancy, bad during lactation and bad for children <8
Levofloxacin, Moxifloxacin
Treatment for: -Resp infections of lower airway- including the atypical pathogens -Quinolones- used for pneumonia and prostatitis Side effects: -Tendon ruptures in patients who are getting older and are on steroids (which already weaken tendons)- when giving someone this med, need to counsel them to take it easy until they are done- the median time to rupture is 6 days
Cloxacillin
Treatment for: -S. aureus (best choice of med if its not MRSA) -GAS/Pharyngitis
Clindamyacin
Treatment for: -Staph and Strep- skin/soft tissue infections -Same effect on MRSA orally (outpatient) -treatment for acne Side effects: -Most famous cause of C. diff infection (because it effects B. fragilis, one of the most important colonic flora)
piperacillin/tazobactam
Treatment for: -it works for everything- because it works for everything we only want to use it in worst cases to avoid resistance -INCLUDING pseudomonas (important) -Can be used for multidrug infections -if we suspect MRSA but aren't sure we could give this plus IV vanco
TMP/SMX
Treatment for: -oral activity against MRSA -Used for STIs -broad spectrum with activity against gram-positive cocci, and gram-negative bacilli (skin/soft tissue) -prophylaxis in neutropenic patients Side effects: -hypersensitivity reactions are common (rashes, seizures, anaphylaxis, infections, bleeding)
Ciprofloxacin
Treatment for: -pseudomonas! Only oral antibiotic that treats this -Fairly broad spectrum, not great for S. aureus or GAS -World standard treatment for prostate infections (because it is a zwitterion and will get in the prostate) -E.coli is becoming more and more resistant to this -also used to treat pyelonephritis
Ceftobiprole
Treats MRSA
Antimicrobial treatment in bacteria vs virus
antibiotics can be bad so especially URTI make sure you only give antibiotics when you know its bacteria
Effects of antimicrobial therapy on normal human microbiota
kills it all! -also leaves antibiotic resistant bacteria all over
What about S. aureus causes food poisioning
the enterotoxin. In a potato salad for example it can be liberated by the bacteria and then when people eat it itll interact with the abdominal viscera and cause vomiting and diarrhea by signaling the brain via vagus or parasympathetics
Why do hospitals have a screening policy for MRSA and VRE
to prevent nosocomial infections- these two bacteria increase morbidity and mortality rates in hospitalized patients. Use of more expensive drugs also may then result
