Cell wall antibiotics Flashcards
Describe the goal of antimicrobial chemotherapy
To provide an adequate amount of active drug at the site of infection to help eliminate invading pathogens in your patient
Describe time dependent killing
Time above MIC is the parameter that predicts efficacy (ex beta lactams)
Describe concentration dependent killing
Peak/MIC and AUC/MIC ratios are the parameters that predict efficacy (ex aminoglycosides- don’t need drug to be in system for long time, just need high peak concentration)
List three “cardinal truths” about antibiotics
- They are a lot easier to start than to stop
- Most problems have > 1 acceptable solutions
- Some problems have only 1 acceptable solution
List five general mechanisms of resistance
- enzyme inactivation (ex beta lactamase)
- alteration in target site (ex PBPs)
- altered bacterial membrane
- efflux pumps (more common in Gram -)
- environmental (ex oxygen tension- metrondiazole works in anaerobic env, aminoglycosides owrk in aerobic env)
List the two emerging carbapenem resistant Enterobacteriacae
Klebsiella producing carbapenemase (KPC) and New Delhi Metallo Beta Lactamase 1 (NDM-1)
List four classes of antibiotics that are considered beta lactams
penicillins
cephalosporins
carbapenems
monobactams
List one glycopeptide antibiotic
vancomycin
List one cyclic lipopeptide antibiotic
daptomycin
Beta lactams are ____ antibiotics- they cause bacterial cell death
cidal
List three steps in beta lactam mechanism of action
- Penetration and binding to Penicillin Binding Proteins (PBPs)
- Inhibition of transpeptidation so that peptidoglycan cross-linking cannot occur
- Loss of cell wall integrity ignites cell autolysis (inhibition of the inhibitor)
In Gram negative organisms, antibiotic must pass through a ____ before binding to PBPs. In gram positive organisms, the antibiotic diffuses directly across peptidoglycan and binds to PBP
porin
List some organisms that natural penicillin is effective against
Gram positives: strep, enterococci, pneumococci, peptostreptococci, listeria, clostridia
Gram negatives: pasturella, Neisseria
Spirochetes: T. pallidum, Borrelia
List clinical uses of natural penicillin
Strep infections, enterococcal infections, meningococcal infections, all stages of syphilis, gas gangrene, periodontal infection
List two aminopenicillins
Amoxicillin (oral) and ampicillin (IV)
Describe the spectrum of coverage of aminopenicillins
Same as penicillin (strep, enterococci, pneumococci, peptostreptococci, listeria, clostridia, pasturella, Neisseria, T. pallidum, Borrelia)
PLUS E coli, proteus mirabilis, hemophilus
Describe clinical uses of aminopenicillins
upper and lower respiratory tract infection, UTI, enterococcal infection, listeria, endocarditis prophylaxis
List four semi-synthetic penicillins
dicloxacillin (oral)
nafcillin, oxacillin, methicillin (IV)
Semi-synthetic penicillins have a niche role in treating ________
Staphylococci
Semi-synthetic penicillins have NO coverage for _____ or Gram ______ organisms
anaerobes, Gram -
List two extended spectrum penicillins
ticarcillin and piperacillin
Describe the spectrum of coverage of the extended spectrum penicillins
Gram negative aerobes
Pseudomonas
Some enterococci, strep, staph
Explain why extended spectrum penicillins are not commonly used in practice
Rarely used in this form as the beta-lactamase inhibitor combination versions are used instead
Describe possible uses of extended spectrum penicillins
Pseudomonas, polymicrobial infections, nosocomial infections
List four penicillin + beta lactamase inhibitor combinations
Oral: amoxicillin-clavulanic acid
IV: ampicillin- sulbactam; ticarcillin-clavulanic acid; pipercillin-tazobactam
Describe the spectrum of penicillin + beta lactamase inhibitor combinations
Same as parent penicillin PLUS
S aureus, E coli, H influenzae, Moraxella, Klebsiella, Bacteriodes, etc
Describe clinical uses of penicillin + beta lactamase inhibitor combinations
Upper and lower respiratory tract infections, head and neck, cellulitis, abscess, pasteurella, intra-abdominal infections, nosocomial infections, Pseudomonas
Describe adverse effects of penicillins
Rash, hypersensitivity, diarrhea, interstitial nephritis
- nafcillin- neutropenia, phlebitis
- ticarcillin/ piperacillin- high salt load
List two first generation cephalosporins
cephalexin (oral)
cefazolin (IV)
Describe the spectrum of coverage of cephalexin
First generation cephaolsporin
Gram positive cocci, strep, staph, E coli, Klebsiella