indication

For the treatment of acute and chronic infections of the upper and lower urinary tract and in asymptomatic bacteriuria due to susceptible strains of bacteria.

pharmacology

Carbenicillin is a semisynthetic penicillin. Though carbenicillin provides substantial in vitro activity against a variety of both gram-positive and gram-negative microorganisms, the most important aspect of its profile is in its antipseudomonal and antiproteal activity. Because of the high urine levels obtained following administration, carbenicillin has demonstrated clinical efficacy in urinary infections due to susceptible strains of: Escherichia coli, Proteus mirabilis, Proteus vulgaris, Morganella morganii, Pseudomonas species, Providencia rettgeri, Enterobacter species, and Enterococci (S. faecalis).

mechanism of action

Free carbenicillin is the predominant pharmacologically active fraction of the salt. Carbenicillin exerts its antibacterial activity by interference with final cell wall synthesis of susceptible bacteria. Penicillins acylate the penicillin-sensitive transpeptidase C-terminal domain by opening the lactam ring. This inactivation of the enzyme prevents the formation of a cross-link of two linear peptidoglycan strands, inhibiting the third and last stage of bacterial cell wall synthesis. Cell lysis is then mediated by bacterial cell wall autolytic enzymes such as autolysins; it is possible that carbenicillin interferes with an autolysin inhibitor.

toxicity

Carbenicillin blood levels achievable are very low, and toxic reactions as a function of overdosage should not occur systematically. The oral LD₅₀ in mice is 3,600 mg/kg, in rats 2,000 mg/kg, and in dogs is in excess of 500 mg/kg. The lethal human dose is not known. Symptoms of overdose include diarrhea, nausea, stomach upset, and vomiting.

biotransformation

Minimal.

absorption

Rapidly absorbed from the small intestine following oral administration. Oral bioavailability is 30 to 40%.

half life

1 hour

drug interactions

Demeclocycline: Possible antagonism of action

Doxycycline: Possible antagonism of action

Mestranol: This anti-infectious agent could decreases the effect of the oral contraceptive

Methacycline: Possible antagonism of action

Methotrexate: The penicillin increases the effect and toxicity of methotrexate

Minocycline: Possible antagonism of action

Oxytetracycline: Possible antagonism of action

Rolitetracycline: Possible antagonism of action

Tetracycline: Possible antagonism of action