Pharmacology for APNs, Study Guide - ANTIMICROBIALS
Antimicrobials
Signs/symptoms of infection
o Fever
o Increased WBC
0 Bacterial: inc. granulocytes, neutrophils (when neutrophils are dec = BAD SIGN)
o Local: Pain, edema, erythema, purulent drainage
0 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
0 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)
0 Morphology: used to distinguish bacteria prior to culturing it
0 Gram stain: + or—
= Gram-positive = violet/purple
= Gram-negative = pink
0 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,
0 Host factors
= Organism susceptibility
= Severity/acuity of illness
= Comorbidities
= Allergy/ADE
= Renal/hepatic function
= Pediatric/elderly/pregnancy/lactation?
= 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
0 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
0 Broad spectrum (empiric/presumptive therapy)
= Against “broad spectrum” microbes
= Unknown pathogen used in possible life-threatening infection
¢ 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
May delay emergence of resistance
o oo o
oo
Good for multiple pathogens = synergistic effect
Blockade/inhibition of growth
Enhanced drug uptake
Cost
Can contribute to emergence of resistance!!!
0 Polypharm > drug-drug interactions - CYP450 implications
¢ Evaluation of therapeutic response
o0 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
e 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
e Organism susceptibility, - MIC, - how to interpret MBC
0 MIC: lowest concentration of antibiotic that will _
= 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
0 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
0 Bactericidal activity dependent on time serum concentration
o AUC/MIC ratio
0 More frequent dosing!!!
0 Beta-lactams, macrolides, vancomycin
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
0 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
0 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!!
0 Metronidazole: can’t breastfeed for 12-24 hrs!!
o Category D: amikacin, gentamicin, kanamycin, streptomycin, sulfonamides, tetracyclines,
tigecycline
Antimicrobials
Signs/symptoms of infection
o Fever
o Increased WBC
0 Bacterial: inc. granulocytes, neutrophils (when neutrophils are dec = BAD SIGN)
o Local: Pain, edema, erythema, purulent drainage
0 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
0 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)
0 Morphology: used to distinguish bacteria prior to culturing it
0 Gram stain: + or—
= Gram-positive = violet/purple
= Gram-negative = pink
0 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,
0 Host factors
= Organism susceptibility
= Severity/acuity of illness
= Comorbidities
= Allergy/ADE
= Renal/hepatic function
= Pediatric/elderly/pregnancy/lactation?
= 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
0 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
0 Broad spectrum (empiric/presumptive therapy)
= Against “broad spectrum” microbes
= Unknown pathogen used in possible life-threatening infection
¢ 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
May delay emergence of resistance
o oo o
oo
Good for multiple pathogens = synergistic effect
Blockade/inhibition of growth
Enhanced drug uptake
Cost
Can contribute to emergence of resistance!!!
0 Polypharm > drug-drug interactions - CYP450 implications
¢ Evaluation of therapeutic response
o0 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
e 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
e Organism susceptibility, - MIC, - how to interpret MBC
0 MIC: lowest concentration of antibiotic that will _
= 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
0 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
0 Bactericidal activity dependent on time serum concentration
o AUC/MIC ratio
0 More frequent dosing!!!
0 Beta-lactams, macrolides, vancomycin
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
0 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
0 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!!
0 Metronidazole: can’t breastfeed for 12-24 hrs!!
o Category D: amikacin, gentamicin, kanamycin, streptomycin, sulfonamides, tetracyclines,
tigecycline
