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34 Cards in this Set

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Stage 1 of cell wall synthesis
- occurs in the cytoplasm and results in the synthesis of MurNAc-pentapeptide
- D-cycloserine
Stage 2 of cell wall synthesis
occurs on the membrane surface and results in synthesis of MurNAc-GlcNAc its attachement
- Vancomycin and Bacitracin
Stage 3 of cell wall synthesis
- occurs in the periplasm (-) or on the outside (+)
– it requires no energy
- cross-linking enzymes exchange the DADA peptide bond for a DAG peptide cross-link
B-lactam mechanism
- structural similarity to the DADA carboxyl terminus
- react w/ PBP's to form a stable complex & inactivate
efficacy of b-lactams in (+) vs (-)
- in (+), depends on ability to bind PBP
- in (-), depends on ability to bind PBP and ability to cross outer membrane
Resistance to B-lactams (5)
- Production of a B-lactamase
- ↓ perm of outer membrane
- express efflux pump
- inability to activate autolytic enzymes
- mutations in PBP's
what organisms produce B-lactamase?
- Staph aureus
- H. influenzae
- N. gonorrhoeae
- (-) enteric rods
what organisms tend to express efflux pumps for B-lactams?
- N. gonorrhoeae
- P. aeruginosa
- S. typhimirium
- usually in concert w/ ß-lactamase, porin mutations and mutations in PBPs
what organisms tend to have the inability to activate autolytic enzymes (and are resistant to B-lactams)
- staph
- strep
- listeria
- makes Ab static and not cidal
what organisms tend to have mutations in PBP's
- staph aureus
- N. gonorrhoeae
- H. influenzae
- Strep pneumoniae
resistance to vancomycin
- Only in E. faecium and E. faecalis
- plasmid mediated
- genes form a depsipeptide that vancomycin can't recognize
vancomycin mechanism
binds w/ high affinity to DADA carboxyl terminus to prevent incorporation in stage 2
Vancomycin Pharmacokinetics
- oral if GI infections (poorly absorbed)
– IV if other
– 6 hr half life
– eliminated unchanged in kidney
vancomycin toxic effects
- Severe ototoxicity and nephrotoxicity if high []’s
- Hypersensitivity reactions ovserved
vancomycin antimicrobial activity
- 1st choice for MRSA and pen-resistant Strep pneum (can be in combo w/ 3rd gen or rifampin)
- alternative for Staph aureus, various Strep, C. difficile
Penicillin pharmokinetics
- widely distributed except CSF, eyes, prostate
- penV, oxacillin, amoxicillin are oral
- penG, piperacillin, ticarcillin are parenteral
– minial metabolism and renal excretion
Penicillin side effects
- Anaphylaxis
- hypersensitivity
- neurotoxicity
PenG and PenV for (+) cocci
- strep groups A, B, C, and G
- E. faecium and E. faecalis (endocarditis and only w/ a aminoglycoside)
- Strep pneum (pneumococcus or diplococcus - resistant strains becoming more common)
PenG and PenV for (+) bacilli
- anthrax
- C. perfringens
- C. tentani
PenG and PenV for (-) cocci
– N. meningitidis
PenG and PenV for enteric (-) bacilli
- syphilis and other spirochetes
- Actinomycetes israelii
- V is an alternative to G for treating Strep. A, B, C, and G and pneumoniae
PenG and PenV antimicrobial spectrum (only groups)
- (+) cocci
- (+) bacilli
- (-) cocci
- enteric (-) bacilli
Penicillinase-resistant penicillins
- for penicillinase-producing Staph
- oxacillin & nafcillin
ampicillin and ampillin + sulbactam
- oral, penicillinase susceptilbe
– good for penG bacteria, and GDS
– also for (-) bacilli like H. influenzae, E. coli, P. mirabilis, Shigella and S. typhi
amoxicillin & amoxicillin + clavulanate
– oral, penicillinase susceptilbe
– good for penG ones, and GDS – also for (-) bacilli like H. influenzae, E. coli, P. mirabilis, Shigella and S. typhi
ticarcillin and ticarcillin + clavulanate
- IV, penicillinase susceptilbe
– good in P. aeruginosa
– alternative for aerobic (-) bacilli like E. coli and Proteus mirabilis
piperacillin and piperacillin + tazobactam
- used parenterally, good in 50% of Klebsiella and some (-) bacilli (if serious, add aminoglyocside)
- penicillinase susceptilbe
- T is a B-lactimatase inhibitor
cephalexin
- 1st generation cephalo
– best against (+) cocci
– use for surface infections
– give orally
cefuroxime
- 2nd generation cephalo
– best for (-) like sinusitis, otitis or LRIs like H. influenzae, B. fragilis and N. gonorrhoeae
– Parenteral admin
ceftriaxone
- 3rd generation cephalo
- good for (-) bacilli like H. flu and N. gonorrhoeae
- can cross BBB so good foor E. coli or K. pneumoniae
- good for meningitis w/ (-) bacilli (P aeruginosa)
- parenteral admin
cefotaxime
- 3rd generation cephalo
- good for (-) bacilli like H. flu and N. gonorrhoeae
- can cross BBB so good foor E. coli or K. pneumoniae
- good for meningitis w/ (-) bacilli (P aeruginosa)
- parenteral admin
ceftazidime
- 3rd generation cephalo
- good for (-) bacilli like H. flu and N. gonorrhoeae
- can cross BBB so good foor E. coli or K. pneumoniae
- parenteral admin
cephalospoin considerations
- don’t give if hx of Pen anapyhlaxis
– ok if hypersensitiviy or resistance
cephalospoin side effects
- pain when given IM
- disulfiram-like reaction w/ alcohol
- hypoprothrombinemia and serious bleeding
– risk of superinfections is ↑ w/ 2nd and 3rd generation