Inhibitors Of Cell Wall Synthesis Flashcards
Beta-Lactam structure
Essential for activity
structural analog of D-Ala-D-ALA residue of NAM/NAG
Beta-lactam ring has high affinity for
Bacterial PBPs
Beta-lactam mechanism of action
T>MIC
Irreversible inhibition of PBPs=autolysin activation
Penicillin resistance due to
decreased permeability
Mutation in PBPs (G+ strains)
Enzymatic inactivation (beta-lactamase, ex.ESBL)
Penicillin G and V are active against
G+ cocci/bacilli
Anaerobes
NOT G- cocci, beta-lactamase producing strains
Penicillin G is given
IV or IM
Penicillin V is given
Orally
Nafcillin is active against
PCN G-resistant methicillin susceptible staph (MSSA) and streptococci
Methicillin is not used because
It causes acute interstitial nephritis
MRSA has emerged due to
Altered PBPs
PBP2/mecA is resistant to all beta-lactams except
Ceftaroline
Amoxacillin is active against G- bacilli due to
Charged amino group that enables transfer though outer membrane porins
Piperacillin-tazobactam has better activity against G- strains (notably P. Auriginosa) due to
Modified amino-PCN R group
Clavulate and tazobactam role
Protect antibiotics from inactivation by beta-lactamases in G- bacteria
Beta lactamase have _ half lives
Short
Penicillin G benzathine is given_
IM weekly
_ prolongs penicillin duration by extending half life
Probenecid
Adverse reactions of penicillins include
Nausea/diarrhea
Maculopapular rashes (amino penicillins-amoxacillin, esp in people with EBV)
Allergy- urticarial rash
Aminopenicillins
Amoxacillin
Extended-spectrum penicillins (aka anti-pseudomonal)
Piperacillin-tazobactam
Beta-lactamase inhibitors
Clavulanate
Tazobactam
Cephalosporin resistance due to
Production of beta-lactamases and altered PBPs
1st generation cephalosporin
Ceftazolin
Ceftazolin is used for
Prophylaxis against surgical site infections (MSSA and strep)
2nd generation cephalosporin
Cefoxitin (subgroups- cephamycins and cephalosporins)
3rd generation cephalosporin
Ceftriaxone
Ceftriaxone is useful for treating
G- meningitis (ESBL bacteria are resistant)
5th generation cephalosporin
Ceftaroline
_ is the only beta lactam active against MRSA
Ceftaroline
Carbapenems
Imipenem-cilastatin
_ are highly resistant to inactivation by beta lactamase
Carbapenems
Carbapenems are given
Parenterally and eliminated by kidneys
Imipenem is combined with cilastatin to
Block host renal inactivation
Carbapenems are used for
Resistant infections
Anaerobics
Mixed infections
Monobactams
Aztreonam
Aztreonam is only active against
G- aerobes
Glycopeptides
Vancomycin
Glycopeptides mechanism of action
Bactericidal
AUC/MIC
Binds D-ALA-D-ALA of NAM blocking addition to the chain
Vancomycin is only active against
G+
Only given orally for C. Diff
Vacomyicin is _toxic
Oto and nephro
Can also cause flushing reaction
Phosphoenolpyruvate analogs
Fosfomycin
Fosfomycin mechanism of action
Inhibits production of Mur A enzyme which synthesizes NAM
Enter bacteria via glycerophosphate transporter (not present in mammals
Fosfomycin is only used against
Urinary pathogens
Beta lactam inhibitors of cell wall synthesis
Penicillin V, G
Nafcillin
Amoxicillin (-clavulonate)
Piperacillin-tazobactam
Cefazolin
Cefoxitin
Ceftriaxone
Cefepime
Ceftaroline
Imipenem-cilastatin
Aztreonam
Non-beta-lactam cell wall synthesis inhibitors
Vancomycin
Fosfomycin