Antimicrobials
Signs/symptoms of infection
o Fever
o Increased WBC
o Bacterial: inc. granulocytes, neutrophils (when neutrophils are dec = BAD SIGN)
o Local: Pain, edema, erythema, purulent drainage
o Systemic: abnormal VS, inc. temp/HR, dec. BP
o *** frail/elderly may not present with these S/S – might not be eating, confusion, lethargy
Classes of microorganisms
o Bacterial, viral, fungal, parasitic!!!
Classifications of antimicrobials
o Antibacterial, antiviral, antifungal, antiparasitic agents!!
o Classified via…
Pharmacologic class, antimicrobial spectrum, biochemical pathway targeted, chemical
structure of pharmacophore
Identification of bacteria (morphology, gram stain, aerobic/anaerobic organisms)
o Morphology: used to distinguish bacteria prior to culturing it
o Gram stain: + or –
Gram-positive = violet/purple
Gram-negative = pink
o Aerobic/anaerobic
Aerobic: requires oxygen!!
Most common infections
Gram +: staphylocci MRS, streptococci, enterococcus VRE
Gram -: Moraxella catarrhalis, Neisseria gonorrhoeae, haemophilius influenza
SPACE bugs are hard to get rid of!!
Anaerobic: thrive w/o oxygen!!!
Local microbiota enter previously sterile tissue
Common anaerobes: clostridium perringes (C Diff), fusobacterium,
actinomyces, bacteroides fragilis (intraabdominal infections/bacteremia)
Considerations in antimicrobial agent selection- host, drug and other factors,
o Host factors
Organism susceptibility
Severity/acuity of illness
Comorbidities
Allergy/ADE
Renal/hepatic function
Pediatric/elderly/pregnancy/lactation?
o Drug
Risk vs benefit
Site of infection for agent penetration
Combination therapies (can be synergistic)
Bacteriocidal or bacteriostatic
Concentration or time-dependent killing
Cost
, Spectrum of activity- difference between narrow, extended and broad-spectrum agents
o Narrow-spectrum = IDEAL!!
Act only on single/limited group of microorganisms
Known pathogen – decrease level of MRSA chance
o Extended-spectrum
Effective against large numbers of gram+/gram- organisms
o Broad spectrum (empiric/presumptive therapy)
Against “broad spectrum” microbes
Unknown pathogen used in possible life-threatening infection
Risk for superinfections
Concept of antimicrobial prophylaxis
o Treatment for prevention of infection
Preoperatively for joint replacements, mechanical valve, etc.
Organ transplant
Immunosuppression
Pre-dental procedures
Risks/Benefits of combination therapy
o Indicated in severe infections
o May delay emergence of resistance
o Good for multiple pathogens = synergistic effect
o Blockade/inhibition of growth
o Enhanced drug uptake
o Cost
o Can contribute to emergence of resistance!!!
o Polypharm drug-drug interactions CYP450 implications
Evaluation of therapeutic response
o Review patient status always narrow spectrum if possible!!!
o Physical S/S, diagnostics
o Lack of response?
Wrong drug/dose/tissue concentration? Wrong bug? Is it MDR?
Host factors
Systematic approach for antimicrobial selection
Understand the following and be able to apply the concepts to a clinical situation
Understand the principles of treating infections based on Gram stain results and Culture/sensitivity results
Organism susceptibility, - MIC, - how to interpret MBC
o MIC: lowest concentration of antibiotic that will inhibit bacterial growth
Interpretation usually categorizes each result as…
Susceptible (S): bacterial strain susceptible when pathogen inhibited in Vitro by
concentration of drug associated with a high likelihood of therapeutic success
Intermediate (I): concentration of drug associated with uncertain therapeutic
effect
Resistance (R): strain considered resistant when concentration of drug
associated with a high likelihood of therapeutic failure
o MBC: the lowest concentration of a drug that kills the bacteria
, o Breakpoint MIC
clinical pharmacology of drug and susceptibility of organism
approximation of drug concentration safely achieved using standard dose/routes
Concentration-dependent killing – bacteriocidal
o Increase kill rate w/ increase concentration
o Allows daily dose w/ increase peak levels
o Aminoglycosides, quinolones
Time-dependent killing – bacteriocidal
o Bactericidal activity dependent on time serum concentration
o AUC/MIC ratio
o More frequent dosing!!!
o Beta-lactams, macrolides, vancomycin
Post antibiotic effect
o Antibacterial effect that persists after drug concentration falls below the MIC
Chemotherapeutic spectra (antimicrobial spectrum of activity)
Combination therapy
Synergy
Spectrum of antimicrobial activity
Antimicrobial prophylaxis
Resistance
Superinfections
o Use of broad-spectrum agents disrupts normal flora and causes the growth of opportunistic
organisms
Empiric regimen
o Initiated before offending organism is identified, sometimes prior to confirmation of an infection
Definitive regimen
o Initiated when causative organism is known
Antibiotic stewardship
o Antibiotic formulary
o Antimicrobial cycling: occurs when antimicrobials are cycled through to make it more effective
after not being used for a while within a population
Susceptibility testing
o Laboratory methods to determine sensitivity of the isolated pathogen to antimicrobial drugs
Follows identification of pathogen (culture)
Predicts MIC!!!
Risks associated with use of antibacterial drugs in pregnancy and lactation
o Azithromycin, clindamycin, penicillins = okay!!
o Metronidazole: can’t breastfeed for 12-24 hrs!!
o Category D: amikacin, gentamicin, kanamycin, streptomycin, sulfonamides, tetracyclines,
tigecycline