Antimicrobials & Neuropharmacology Exam with Complete Solution
Pharmacology for APNs, Study Guide - ANTIMICROBIALS
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