Carbenicillin in patients with cystic fibrosis:Clinical pharmacology and therapeutic evaluation

Abstract

Carbenicillin, a new semisynthetic penicillin (alpha-carboxybenzylpenicillin) with activity against Pseudomonas aeruginosa, has been studied. Forty per cent of 110 strains of P. aeruginosa and most strains of Proteus mirabilis and Proteus morganii were susceptible to 62.5 μg per milliliter or less of carbenicillin. Of strains of Staphylococcus aureus tested, the majority were inhibited by 6.25 μg per milliliter of less of carbenicillin. Concurrent administration of probenecid is necessary to maintain effective serum levels for 2 to 4 hours after an intravenous dose. About 80 per cent of an intravenous dose is excreted in urine within 4 hours. Only 1 per cent of the antibiotic inhaled as an aerosol is recovered in urine. Fifty-four patients with cystic fibrosis, during 85 episodes of acute exacerbations of their pulmonary infections, had favorable clinical and radiologic responses to carbenicillin therapy. Transient elimination of P. aeruginosa was achieved in a small number of patients, but there was a striking increase in isolation of Klebsiella pneumoniae in end-treatment cultures. A rise of serum glutamic oxaloacetic transaminase activity was found in 40 per cent of the patients treated. Carbenicillin, a new semisynthetic penicillin (alpha-carboxybenzylpenicillin) with activity against Pseudomonas aeruginosa, has been studied. Forty per cent of 110 strains of P. aeruginosa and most strains of Proteus mirabilis and Proteus morganii were susceptible to 62.5 μg per milliliter or less of carbenicillin. Of strains of Staphylococcus aureus tested, the majority were inhibited by 6.25 μg per milliliter of less of carbenicillin. Concurrent administration of probenecid is necessary to maintain effective serum levels for 2 to 4 hours after an intravenous dose. About 80 per cent of an intravenous dose is excreted in urine within 4 hours. Only 1 per cent of the antibiotic inhaled as an aerosol is recovered in urine. Fifty-four patients with cystic fibrosis, during 85 episodes of acute exacerbations of their pulmonary infections, had favorable clinical and radiologic responses to carbenicillin therapy. Transient elimination of P. aeruginosa was achieved in a small number of patients, but there was a striking increase in isolation of Klebsiella pneumoniae in end-treatment cultures. A rise of serum glutamic oxaloacetic transaminase activity was found in 40 per cent of the patients treated.