Antimicrobials Flashcards
What had biggest effect on human life expectancy?
A. Public health measures, sanitation, and immunization
B. Antimicrobials
A. Public health measures
% of death worldwide due to infectious disease?
10%
How are antibacterials classified?
By MOA
MIC definition?
Lowest concentration of drug that inhibits visible growth
MBC definition?
Lowest concentration of drug that kills bacteria
Define bacteriostatic in terms of MBC and MIC
MBC»_space; MIC
Define bactericidal in terms of MBC and MIC
MBC roughly equals MIC
The lower the MBC/MIC of an organism/drug combo, the ____ the organism.
more susceptible
Methods for determining microbial susceptibility/resistance?
Culture based (disk diffusion and E-test) or molecular detection of resistance mutations (i.e. PCR)
What is a hospital antibiogram?
Summary of antibiotic susceptibilities in your own site to track resistance trends
Pharmacodynamics is…
the biological effects of the drug on the body (i.e. time course and intensity of therapeutic and adverse effects)
Pharmacokinetics is…
the body’s effect on the drug (i.e. time course of absorption, distribution, metabolism, and excretion)
Cmax is?
Peak concentration of drug in body
AUC is?
Area under the curve
Time dependent killing goal?
Maximize time above the MIC; you want serum [drug] above MIC for at least 50% of dosing interval
Beta lactam MOA?
bind PBP and inhibit peptidoglycan synthesis
Name the 5 beta lactam subclasses
penicillins, carbapenems, monobactams, clavulanic acid, cephalosporins
Glycopeptides MOA?
inhibit transglycosylase activity in peptidoglycan synthesis
Function of PBPs?
make peptidoglycan
PBPs must have ____ function, and may also have ____ function.
peptidyltransferase; transglycosylase
Penicillin resembles…
D-Ala D-Ala moiety
Concentration-dependent killing goal?
Maximize Cmax and therefore AUC
Drugs with TDK MOA?
Penicillins, Cephalosporins, Macrolides, Clindamycin
Drugs with CDK MOA?
Fluoroquinolones, Aminoglycosides
Post antibiotic effect is…
time it takes bacteria to return to log phase growth after removal of abx
Bacteria with longer PAEs require need ___ frequencies of dosing.
lower
Which generally needs longer PAE? CDK or TDK?
CDK
Which generally needs longer PAE? Gram + or -?
Gram +
What are the three main antibiotic resistance mechanisms?
Enzymatically inactivate drug, alter drug target, alter drug exposure
What does beta-lactamase do?
Enzymatically inactivate beta-lactams
What does clavulanic acid do?
Inhibits beta-lactamase, overcome abx resistance
2 beta-lactamases to know?
ESBL (extended spectrum beta lactamases) and Metal-dependent/New Delhi
What is the “nuclear option” for beta-lactam resistance?
PBP mutation that alters affinity for beta-lactams, but still retain transpeptidase activity
Prioritize choosing abx with ____ fitness cost for resistance
higher
Gram ___ bacteria alter their membrane permeability to pump out abx
negative
2 ways to alter drug exposure?
decrease membrane permeability; increase efflux of drug to shoot out of cell
Main abx resistance mechanism for vancomycin?
Alter D-Ala D-Ala slightly with lac so that vancomycin cannot bind precursor.
Lipopeptides MOA?
disrupt cell membrane of G+ by binding phosphatidyl-glycerol forming pores
Why are lipopeptides specific?
Phosphatidyl-glycerol is abundant in bac cells but not human cells
What part of body should lipopeptides not be used to treat?
Lungs (surfactant)
Main lipopeptide to know?
Daptomycin
Main class of folate synthesis inhibitors?
Sulfonamides
Main sulfonamide to know?
Sulfamethoxazole
Are sulfonamides bacteriostatic or bactericidal?
Bacteriostatic, combine with trimethoprim to make bactericidal
Are fluoroquinolones bacteriostatic or bactericidal?
Bactericidal
Fluoroquinolone resistance is usually via ____ and/or ___
altering the drug target (mutations in topoisomerase genes); altering the drug exposure by decreasing uptake
Rifamycins MOA?
inhibit mRNA synthesis by binding DNA dep RNA Pol
Rifamycins bacteriostatic or bactericidal?
Either! Depends on concentration
Rifamycin to know?
Rifampin
Rifamycin is rarely used alone because it quickly develops abx resistance by ____
mutations in RNA polymerase gene (altered drug target)
2 main classes of drugs that damage DNA?
fluoroquinolones and nitroimidazoles
Main nitroimidazole to know?
metronidazole
Nitroimidazole MOA?
forms free radicals that damage DNA
Which class of abx is a prodrug? What does this mean?
nitroimidazoles - must be activated by microbial enzymes
Most likely cause of abx resistance in nitroimidazoles?
mutations in microbial enzymes that convert prodrug to active compound
Name all the classes of 30S ribosome antibiotics.
tetracyclines, aminoglycosides
Name the 2 important tetracyclines to know.
Tetracycline, doxycycline
Name the 2 important aminoglycosides to know.
gentamycin, streptomycin
Name the 2 classes of abx used for anaerobic microbes exclusively. Which one is bacteriostatic and which one is bactericidal?
Lincosamides, nitroimidazoles; lincosamides = static, nitroimidazoles = cidal
Aminoglycosides should not be used in what part of the body and why?
the GI tract; will be ineffective because anaerobes are intrinsically resistant
Tetracycline is bacteriostatic or bactericidal?
Bacteriostatic
Bacteriostatic drugs + bactericidal drugs = ?
Antagonistic effect
5 classes of abx that bind 50S subunit?
oxazolidenones, streptomycins, lincosamides, macrolides, chloramphenicol
Clindamycin falls under what class of antibiotic?
Lincosamide
2 main types of macrolides to know?
erythromycin, azithromycin
MLSb resistance is associated with which abx? Why does it happen?
macrolides, lincosamides, and streptogramins; similar MOA
What does the D test detect?
inducible clindamycin resistance
Main oxazolidinone to know?
linezolid
