Bacterial Cell Wall Synthesis Inhibitors Flashcards
Classes of bacterial cell wall synthesis inhibitors & examples
Beta Lactams
- Penicillins (penicillin, cloxacillin, amoxicillin, ampicillin, piperacillin, methicillin)
- Oxapenems (clavulanic acid + amoxicillin, sulbactam + ampicillin, tazobactam + piperacillin)
- Cephalosporins (cephalexin, cefuroxime axetil, ceftriaxone, cefepime)
- Carbapenems (imipenem, meropenem)
- Monobactams (aztreonam - azactam)
Non-beta Lactams
6. Vancomycin
Functions of peptidoglycan (murein) (3)
- Involved in binary fission of bacteria
- Gives structural strength to cell wall
- Counteracts osmotic pressure of cytoplasm
Mechanism of action of beta lactams
Bactericidal effect on bacteria during binary fission
- Bind covalently to the active site of the enzyme, transpeptidase (or penicillin-binding protein PBP)
- Activate murein hydrolase to cause autolysis of bacteria
Mechanism of resistance to beta lactams (4)
- Production of beta lactamase
- Mutation of transpeptidase gene so beta lactams are unable to bind to them eg MRSA
- Reduced permeability of cell wall due to reduced/altered aquaporins in outer membrane
- Presence of efflux pumps
Toxicity of penicillins (3)
- Allergy/hypersensitivity eg Stevens Johnson syndrome, TEN - products of degradation combines w host proteins - activates Ab production
- CDAD - ampicillin
- Neurotoxicity (convulsions, confusion, hallucinations) - when elevated blood levels occur in renal-impaired patients
Mechanism of action of oxapenems
- Weak antibacterial activity & affinity for beta-lactamases - not used alone
- Beta lactam ring forms a complex with bacterial beta-lactamase - prevents enzyme from destroying beta lactam ring of the co-administered beta lactam antibiotic
Toxicity of cephalosporins (3)
- Hypersensitivity - cross-allergy between cephalosporins & penicillins
- GIT (diarrhea, CDAD)
- Thrombophlebitis - irritation of vessel linings - inflammation, impaired blood flow, platelet accumulation - predispose to thrombosis - thrombus can lead to emboli, AMI, stroke etc
Spectrum of activity & PK of cephalosporins
- Mainly gram pos, some gram neg (enterobactericae (1G), Klebsiella (2G), PAE, gonococcus, meningococcus, H Influenzae, B pseudomallei)
- All renal elimination except ceftriazone (3G) - hepatic
Uses of carbapenems
Most effective beta lactams against anaerobes, able to penetrate gram neg cell envelopes
Meropenem
- Meningitis in children
- Intra-abdominal sepsis/skin infections
Tienam (Imipenem + cilastatin)
- Aerobic & anaerobic infections
- Pseudomonas & enterobacter infections
Toxicity of carbapenems (4)
- GIT (nausea, vomiting, diarrhea) - more with Tienam
- Rash
- Superinfections
- Seizures - rare
PK of monobactams
- Parenteral administration only
- Widely distributed, penetrates BBB when meninges are inflamed
- only small % metabolised in the liver, 60-70% renally excreted
Uses & toxicity of monobactams (1+2)
- Only gram neg aerobic
- Occasional skin rash
- Transaminasemia (increased AST & ALT)
- Little/no cross-sensitivity with other penicillins
Mechanism of action of vancomycin
Binds via high affinity H bonds to peptide components of amino sugars in peptidoglycan & prevents them from interacting with transglycosylase
Spectrum of activity & uses of vancomycin (2+4)
- Gram pos including MRSA, beta lactamase producing staph, C diff
- Combined with ceftriaxone - treats N. meningitidis & H. influenzae in infants
- Serious allergy to penicillin
- Pseudomembrane colitis esp if unresponsive to metronidazole
- Prophylaxis - endocarditis, implantation of prosthesis, in institutions with increased rate of MRSA
- Empiric for MRSA infection
Toxicity of vancomycin (3)
- Thrombophlebitis, fevers, chills (10%)
- Red neck/Redman syndrome (rash when infusion too rapid - prolong duration)
- Nephrotoxicity & ototoxicity - rare) - (A) with another oto/nephrotoxic agent eg aminoglycoside (B) in renal impaired patients
