Chemotherapy (Lec 11) Flashcards
Chemo is unique how?
1) selective toxicity (more toxic to parasite than host)
2) selects for resistant strains
3) lowers microorg load so host defense can kill the rest
2 issues with Chemo
1) potential hypersensitivity
2) organ directed toxicity
Mechanisms of drug resistance (6)
1) drug not absorbed
2) drug is inactivated
3) drug pumped out
4) target is modified
5) inc production of targets
6) metabolic pathway bypasses target
Antimicrobial resistance mutation can be passed to other bacteria by what methods? (2)
vertically to daughter cells
horizontally to unrelated cells
3 methods of horizontal transfer of antimicrob resistance mutation?
1) transduction
2) transformation
3) conjugation
Transduction transfer occurs how?
Example of bacteria that uses transduction?
Bacteriophage (virus) transfers the resistant DNA from one bacteria to another.
S. aureus
Transformation transfer occurs how?
Example?
Incorporation of DNA found free in environment into bacteria.
penicillin-resistant pneumococci
neisseria
Conjugation transfer occurs how?
Example?
Direct cell-to-cell contact through pilus or bridge.
Allows trxn of resistance to multiple drugs.
Gram - bacilli
3 adverse effects of antimicrobial therapy?
1) over-extension of pharmacologic actions
2) organ-directed toxicity
3) hypersensitivity rxns
Chloramphenicol is bactericidal against? (3)
pneumococci
meningococci
h. flu
MIC is?
Minimum Inhibitory Concentration of drug needed to inhibit bacterial growth
MBC is?
Minimum Bactericidal Concentration of drug needed to kill bacteria
Concentration Dependent Killing
bactericidal agents
rate and extent of killing dependent on drug concentration
e.g. aminoglycosides, quinolones
Time Dependent Killing
bactericidal agents
Kill dependent on length of time exposed to drug.
Increase in drug does not increase kill.
e.g. beta-lactams, vancomycin
Postantibiotic Effect (PAE) is?
What enhances PAE?
Persistent suppression of bacterial growth after limited exposure to drug.
Postantibiotic leukocyte enhancement assists this effect
3 mechanisms of synergism
1) Block of sequential steps in metabolism (TMP-SMX)
2) Inhibition of enz inactivation (beta-lactamase inhibitors)
3) Enhancement of drug uptake (penicillin ↑uptake of aminoglycosides)
2 mechanisms of antibiotic antagonism
1) bacteriostatic agent inhibits bacterialcide
2) drug induces enzyme inhibition towards itself
Drug misuses that cause tx failure? (4)
1) antibiotics to treat viral infections
2) antibiotics to treat fevers of unknown origin
3) too low a dose
4) not treating for long enough time period
Superinfections are?
Most frequently seen w/ which antibiotics?
new infection during tx of primary infection
broad spectrum antibiotics
Intestinal candidiasis
fungal
most common superinfection
tx: continue antibiotics, add oral nystatin or amphotericin B
Staph enterocolitis
life threatening superinfection
tx: stop antibiotic, start oral vancomycin
Pseudomembranous colitis
life threatening superinfection
(U) post clindamycin
caused by c. difficile
tx: stop antibiotic, start oral metronidazole or vancomycin
Antibacterial prophylaxis:
surgery
cefazolin
Antibacterial prophylaxis:
HSV
acyclovir
Antibacterial prophylaxis:
Group B strep
ampicillin or penicillin G
Antibacterial prophylaxis:
h flu type B
rifampin
Antibacterial prophylaxis:
malaria
chloroquine
Antibacterial prophylaxis:
meningococci
rifampin
Antibacterial prophylaxis:
pertussis
erythromycin
Antibacterial prophylaxis:
pneomococcemia
penicillin G
Antibacterial prophylaxis:
pneumocystis carinii
TMP-SMZ
trimethoprim-sulfamethoxazole
Antibacterial prophylaxis:
tuberculosis
isoniazid
Antibacterial prophylaxis:
UTI
TMP-SMZ
trimethoprim-sulfamethoxazole
