Antibacterials: Misc Related to B-lactams

Question 1

Clavulanic Acid

Answer 1

• family: B-lactamase inhibitor
• mechanism: Inhibits penicillinase/B-lactamase
• clinical: to overcome antibacterial resistance of penicillins
• toxicity/interactions: increased jaundice and acute hepatitis
• misc: administered with beta lactam family (amoxicillin and ampicillin) to protect them from enzymatic hydrolysis and to extend their antimicrobial spectrum

Question 2

Sulbactam

Answer 2

• family: B-lactamase inhibitor
• mechanism: Inhibits penicillinase/B-lactamase
• clinical: to overcome antibacterial resistance of penicillins
• misc: administered with beta lactam family (amoxicillin and ampicillin) to protect them from enzymatic hydrolysis and to extend their antimicrobial spectrum

Question 3

Imipenem

Answer 3

• family: B-lactam/carbapenem
• mechanism: Binds to PBP (transpeptidase) and prevents cross-linking of peptidoglycan cell wall
• kinetics: IV; administered with CILASTATIN because of susceptibility to renal dihydropeptidase I
• clinical: Reserved for severe life-threatening infections or sepsis; Broad spectrum includes some PRSP strains (not MRSA); Gram ­negative rods; Pseudomonas
• toxicity/interactions: CNS effects (confusion and seizures); Partial cross­reactivity with penicillins
• misc: CILASTATIN always co-administered (inhibits renal dihydropeptidase I)

Question 4

Ertapenem

Answer 4

• family: B-lactam/carbapenem
• mechanism: Binds to PBP (transpeptidase) and prevents cross-linking of peptidoglycan cell wall
• kinetics: IV; NOT affected by renal dihydropeptidase I
• clinical: Reserved for severe life-threatening infections or sepsis; Broad spectrum includes some PRSP strains (not MRSA); Gram ­negative rods; Pseudomonas
• toxicity/interactions: CNS effects (confusion and seizures); Partial cross­reactivity with penicillins
• misc: NOT susceptible to renal dihydropeptidase I

Question 5

Vancomycin

Answer 5

• family: none (antibacterial)
• mechanism: Binds D-ala-D-ala of nascent peptidoglycan pentapeptide and inhibits transglycosylation. This prevents peptidoglycan elongation and cross-linking of the peptidoglycan cell wall.
• kinetics: Parenteral (oral only for bacterial enterocolitis); eliminated in urine w/o modification
• clinical: Drug-resistant gram (+) infections–MRSA; back-up for c. diff
• toxicity/interactions: Chills, fever, phlebitis, ototoxicity, nephrotoxicity, “red man syndrome”; requires dosage modification w/ renal insufficient patients
• misc: Bactericidial

Question 6

Bacitracin

Answer 6

• family: none (antibacterial)
• mechanism: Cyclic polypeptide mixture – inhibits late stages of cell-wall synthesis (interferes with dephosphorylation in cycling of the lipid carrier that transfers peptidoglycan subunits to the growing cell wall)
• kinetics: Topical; poorly absorbed
• clinical: Gram (+)
• toxicity/interactions: neprotoxicity with systemic use
• misc: Topical only (b/c highly nephrotoxic)

Question 7

Cycloserine

Answer 7

• family: none (antibacterial)
• mechanism: Antimetabolite and structural analogue of D-ala – blocks incorporation of D-ala into peptidoglycan side chain
• kinetics: Highly polar
• clinical: Gram (+) and Gram (-) BUT only used on TB
• toxicity/interactions: Neurotoxicity (seizures, tremors, psychosis)
• misc: Only use for TB resistant to first line TB drugs