Principles of Antimicrobial Chemo Flashcards
what 3 classes of antibiotics cause superinfection?
1) broad spectrum penicillins (ampicillin)
2) Cephalosporins- 3rd/4th gen
3) Clindamycin
selective toxicity
antibiotics can kill microbes while having no effect or minimal effect on host cell
Cell wall synthesis inhibitors
4 b-lactams, 2 other
B-lactams:
1) penicillins
2) cephalosporins
3) carbapenems
4) monobactams
Others:
1) vancomycin
2) fosfomycin
protein synthesis inhibitors
1) aminoglycosides
2) macrolides and ketolide
3) clindamycin
4) tetracyclines and glycylcyclines
5) streptogramins
6) other (chlroamphenicol, Linezolid)
inhibitors of nucleic acid synthesis or function
1) sulfonamides
2) trimethoprim
3) fluroquinolones
4) nitroimidazoles (metronidazole)
antimycobacterial drugs
Rifamycins (rifampin)
(aminoglycosides)
(fluoroquinolones)
Others (isoniazid, prazinamide, ethambutol)
Bactericidal drugs
kill sensitive organisms at serum levels achievable in patient so number of viable organisms falls rapidly after exposure to drug
what is the first line treatment for seriously ill or immunocompromised patients?
bactericidal drugs
bacteriostatic drugs
arrests growth and replication of bacteria at serum levels achievable in patient thus limited spread of infection.
6 main bacteriostatic drugs
1) Sulfonamides
2) Macrolides
3) Clindamycin
4) Tetracyclines
5) chloramphenicol
6) Linezolid
MIC (Minimum inhibitory concentration)
lowest concentraiton of antibiotic that inhibits growth of tested bacteria
MBC (Minimum bactericidal concentration)
lowest concentration of antibiotic that kills tested bacteria
concentration dependent killing
+ examples
increase of bacterial killing as blood concentration of bactericidal antibiotics increases
ex: aminoglycosides, fluoroquinolones
time-dependent killing
+ examples
some bactericidal antibiotics do not significantly increase rate of killing as concentration increases
rate of killing is proportional to time the blood concentration remains above the minimum bactericidal concentration.
ex: penicillins, cephalosporins, vanco
postantibiotic effect
+ examples
some antibiotics show persistent suppression of microbial growth after drug plasma levels have fallen below minimum inhibitory concentration.
could be due persistence of drug at binding site and need to synthetize new enzymes before growth can resume
(ex: aminoglycosides and fluroquinolones)
b-lactam (site & MOA)
cell-wall
inhibition of transpeptidases
vancomycin (site & MOA)
cell wall
inhibition of transglycosylase
fofomycin (site & MOA)
inhibition of enolpyruvate transferase
aminoglycosides (site & MOA)
30S
blockade of initiation complex, misreading code of mRNA template, and blockade of translocation reaction
macrolides (site & MOA)
50S
blockade of translocation reaction
Chloramphenicol (site & MOA)
50S
blockade of transpeptidation reaction
Tetracyclines (site & MOA)
30S
blockade of aminoacyl-tRNA binding
Quinupristin (site & MOA)
50S
blockade of translocation reaction
Dalfopristin (site & MOA)
50S
blockade of translocation reaction
Linezolid (site & MOA)
50S
blockade of initiation complex
Sulfonamide (site & MOA)
cytoplasm
inhibition of dihydropteroate syntehtase
Trimethoprim (site & MOA)
cytoplasm
inhibition of dihydrofolate reductase
Quinolones (site & MOA)
cytoplasm
inhibition of topoisomerases
Metronidazole (site & MOA)
DNA
DNA damage
drug resistance can result from what 2 changes in microbial DNA?
1) spontaneous mutation
2) DNA transfer of drug resistance (Plasmid)
What 4 mechanisms are responsible for antimicrobial drug resistance?
1) production of microbial enzymes that inactivate drug (ex: beta-lactamase)
2) development of microbial targets with decreased drug affinity (i.e. decreased topoisomerase affinity, 50S, 30S)
3) decreased drug concentration inside bacteria due to decreased permeability of cell membrane or multidrug efflux pump
4) increased production of essentail metabolite (i.e. PABA)
empiric therapy
antimicrobial treatment without laboratory identification of specific pathogen.
used when:
1) history and site of infection
2) severity of disease requires immediate treatment
specific therapy
specific antimicrobial treatment done after identifying causative pathogen by cultures nad susceptibiliyt testing of sample from infection site
prophylactic therapy
to prevent rather than treat infection. Indiscriminate use of prophylactic therapy can result in bacterial resistance and super infections
impaired immune systems can affect antimicrobail drug therapy. what clinical situations would this include?
1) advanced age
2) DM
3) alcoholism
4) malnutrition
5) HIV
6) immunosuppressive therapy
7) cancer chemo
T or F– bactericidal antibiotics are preferred inpatients with impaired immunity
T
when must surgical drainage occur before proper action of antibiotics can be achieved?
abscesses
why are some antibiotics contraindicated in very young or very old?
becauser renal and hepatic functions are poorly developed in newborns and diminished in elderly
do most antimicrobials cross placenta?
yes
what antibiotics should be avoided during pregnancy? (5 major classes)
1) tetracyclines/glycylcylines
2) aminoglycosides
3) some macrolides
4) fluoroquinolones
5) sulfonamides
direct cytotoxicity
when some antibiotics cause dose-related cytotoxicity to some organs or tissues
allergic reactions and antimicrobials
when some antibiotics or their metabolites have intrinsic ability to induce hypersensitiviy.
most allergenic antibiotics = beta-lactams, sulfonamides, and tetracyclines
drug interactions
mainly due to induction (i.e. by rifampin) or inhibitions (i.e. erythromycin) or metabolism of concamitant drug
superinfection
broad specturm antibiotics can lead to alteration of normal microflora of respiratory, intestinal, and GU tracts leading to opportunistic infections
what are 4 reasons why antibiotic combinations are used?
1) treat empirically severe infections (i.e. endocarditis)
2) delay drug resistance (i.e. TB)
3) treat mixed infection (i.e. periotneal infection)
4) achieve a synergistic effect (i.e. P. aeruginosa)
What are the 3 main mechanims of antibiotic synergism?
1) sequential blockade ( combine duse of drugs may cause inhibition of two steps in a bacterial metabolic pathway– ie.e trimethoprim-sulfametoxazole combo)
2) blockade of drug inactiving enzymes (i.e. clavulanic acid inhibits penicillinases)
3) enhanced bacterial drug uptake (i.e. b-lactam drugs increase bacterial permeability to aminoglycosides)
