Antimicrobial Agents I Flashcards
Bactericidal agents can compensate for pts with _____.
impaired host defenses
Is it beneficial or toxic for clindamycin to accumulate in bone? Why?
beneficial- treat osteomyelitis
What is an important consideration for metronidazole?
drug-drug interaction w/ alcohol due to inhibition of aldehyde metabolism
What are extended spectrum Abx?
effective against gram + AND -
Name the DQ CRIMES.
D- doxycycline Q- quinolones C- clindamycin R- rifampin I- isoniazis M- metronidazole E- erythromycin-like S- sulfonamides
What are the 5 major mechanisms of antibacterial resistance to Abx?
- altered targets 2. enzymatic destruction 3. alternative resistant metabolic pathway 4. decreased entry 5. increased efflux
Name 4 drugs that readily enter the CNS.
- chloramphenicol 2. sulfonamides 3. cephalosporin (3/4) 4. rifampin- metronidazole
What is an important consideration for the sulfonamides?
renal crystalluria
What is an important consideration for isoniazid?
genetic polymorphism of N-acetyl transferase metabolism; potential hepatotoxicity
What is mutational/chromosomal resistance?
multiple steps/generations; each succeeding generation becomes slightly more resistant
Name 2 drugs that have selective/toxic accumulations and where.
- aminoglycosides- inner ear/brush border 2. tetracyclines- bone and teeth
What is an important consideration for doxycycline?
not renally eliminated tetracycline
What drugs should not be used in pregnancy, or with caution? (6)
- aminoglycosides 2. metronidazole 3. chloramphenicol 4. tetracyclines 5. fluoroquinolones 6. voriconazole
Choose: Oral Abx DO/DO NOT cross the placenta.
DO
What is the post-antibiotic effect?
some Abx, like aminoglycosides and fluoroquinolones, continue to kill or inhibit growth or bacteria for several hours after the conc of drug falls below the MIC
What is direct Abx toxicity?
affect host cellular processes
What is transformation?
bacteria picks up free DNA from the environment
Superinfections are more common in those aged ____ or ____.
under 3yo, over 50yo
Bactericidal agents are req for treatment of infections that are _____.
not accessible to host immune system responses
Why are the DQ-CRIMES drugs important?
they have possible drug-drug interactions, genetic polymorphisms, or hepatotoxicity considerations
What are the cell wall synthesis inhibitors?
Penicillins (-cillin, Clavulanic acid) cephalosporins (Cef-) carbapenems (-penem) vancomycin
Abx’s may alter the activity of ____ drug metabolizing enzymes, causing indirect toxicity.
CYP450
Name 4 drugs that have selective/beneficial accumulations and where.
- clindamycin- bone 2. macrolides- pulmonary cells 3. tetracyclines- gingival crevicular fluid and sebum 4. nitrofurantoin- urine
How can resistance be minimized?
only use Abx when need is established; select Abx based on compatibility; use adequate duration and concentration
_____ agent is preferred in severe infections.
Bactericidal
Is it beneficial or toxic for tetracyclines to accumulate in gingival crevicular fluid and sebum? Why?
beneficial- treatment of periodontitis and acne
What is acquired resistance?
selective pressures produce successive generations of organisms with biological traits that minimize drug action
What are the 2 modes of acquired resistance?
- mutational/chromosomal resistance 2. plasma mediated
____ agents are req for treatment of infections that are not accessible to host immune system responses.
Bactericidal
What is concentration dependent killing?
some abx kill bacteria faster when given in doses that result in higher plasma concentrations
____ agents act more quickly and their action is often irreversible.
Bactericidal
What are the broad classifications of antibiotics?
gram + or - cocci; gram + or - rods; gram + or - anaerobes; atypical bacteria
Is it beneficial or toxic for aminoglycoside to accumulate in the inner ear and renal brush border? Why?
toxic- increased tendency for ototoxicity and nephrotoxicity
What determines whether an Abx is bactericidal or bacteriostatic?
mechanism of action/target; conc achieved in vivo; specific microorganism
What are the bacteriostatic mechanisms?
inhibition of protein synthesis (except aminoglycosides); inhibition of intermediary metabolic pathways
Pseudomembranous colitis due to ____ overgrowth can be life-threatening.
Clostridium difficile
What are the inhibitors of DNA function?
fluoroquinolones (-floxacin) nitrofurantoin metronidazole
Bactericidal agent is preferred in ______ infections.
severe
Is it beneficial or toxic for macrolides to accumulate in pulmonary cells? Why?
beneficial- URI treatment
What is an important consideration for clindamycin?
not renally eliminated
_____ means the organisms are killed; ____ means organisms are prevented from growing.
Bactericidal; bacteriostatic
What is an important consideration for the quinolones?
ciprofloxacin is renally cleared but is a non-substrate inhibitor of P450
What kind of bacteria has a large reservoir for plasma-mediated transfer?
gram-negative coliform bacteria
What is an important consideration for rifampin?
induces P450, potential hepatotoxicity
What is transduction?
virus injects resistance to bacteria
What kinds of Abx are most likely to cause superinfections?
broad spectrum
Why are disturbances of host microflora/superinfections?
overgrowth of normally suppressed pathogens b/c of broad spectrum Abx
What is natural resistance?
microbes lack a susceptible target for drug action
Name the 6 narrow spectrum Abx.
- aminoglycosides 2. penicillinase-resistant penicillins 3. clindamycin 4. vancomycin 5. metronidazole 6. penicillin G, V
What are the 3 categories of Abx toxicity?
- direct 2. indirect 3. disturbances of host microflora/superinfections
What is plasma mediated resistance?
extrachromosomal DNA that can confer immediate resistance
What is conjugation?
plasmid transfer between 2 physically attached bacteria
What are broad spectrum Abx?
effective against gram +, gram -, AND atypical organisms
What are the protein synthesis inhibitors?
macrolides (-mycin) tetracyclines clindamycin chloramphenicol aminoglycosides
Which Abx’s are less likely to disturb the host flora?
narrow spectrum
____ agents can compensate for pts with impaired host defenses.
Bactericidal
Name 4 drugs that enter the CNS with inflammation.
- penicillin 2. vancomycin 3. ciprofloxacin 4. tetracycline
Bactericidal means_____; bacteriostatic means _____.
the organisms are killed; organisms are prevented from growing
What is escape?
purines, thymidine, serine, methionine released from purulent infections allows sulfonamide resistance; failure to lyse due to lack of osmotic pressure differences in penicillin resistance
_____ due to Clostridium difficile overgrowth can be life-threatening.
Pseudomembranous colitis
Most antibiotics distribute well into tissues outside the CNS, but vary in their ability to cross the ____.
BBB
Name the 6 broad spectrum Abx.
- macrolides 2. chloramphenicol 3. fluoroquinolones (moxi, gemi) 4. sulfonamides 5. tetracyclines 6. trimethoprim
Name the 4 extended spectrum Abx.
- aminopenicillins (amox, amp) 2. cephalosporins 3. fluoroquinolones 4. carbapenems
Is it beneficial or toxic for nitrofurantoin to accumulate in urine? Why?
beneficial- treatment of UTIs
What is an important consideration for the erythromycin-like drugs?
drug-drug interactions due to inhibition of P450
What are the bactericidal mechanisms?
inhibition of cell wall synthesis; disruption of cell membrane function; interference with DNA function of synthesis
Is it beneficial or toxic for tetracycline to accumulate in bone and teeth? Why?
toxic- causes abnormal bone growth and brownish tooth discoloration in fetuses and young children
What is indirect Abx toxicity?
allergic rxns and hypersensitivities
Where does direct toxicity typically manifest?
GI tract, liver, kidney, nervous system, blood and blood forming system
Which Abx’s require dosage adjustments if renally impaired?
- penicillin 2. cephalosporins 3. vancomycins 4. aminoglycosides 5 fluoroquinolones
What are narrow spectrum Abx?
effective against EITHER gram + or -