Prophylaxis and Therapy for Pseudomonas aeruginosa Infection with Carbenicillin and with Gentamicin

Abstract

A series of 106 strains of Pseudomonas•aeruginosa were sensitive in tube dilution tests to gentamicin (M.I.C. 1 to 4 μg./ ml.) and moderately sensitive to a new semisynthetic penicillin, carbenicillin (M.I.C. 32 to 128 μg./ml.) ; one strain was found to be more sensitive to carbenicillin. Carbenicillin was inactivated by the penicillinase of Staph. aureus. Groups of mice were infected by inoculation of small burns with two strains of Ps. aeruginosa ; about 70% of the mice infected with these strains died with septicaemia. Courses of treatment with carbenicillin gave serum levels in burned or unburned mice up to 128 μg./ml., and the mice were completely protected against both strains. Gentamicin gave peak blood levels in recently burned mice of 64–128 μg./ml. but lower levels (4–8 μg./ml.) in unburned mice ; gentamicin protected the animals against the more sensitive strain of Ps. aeruginosa only (M.I.C. 0.5-1 μg./ml.). Similar results were obtained with treatment by carbenicillin or by gentamicin, starting at the time of infection or 24 hours later. In most experiments colistin sulphomethate gave no evidence of protection. A small controlled trial in progress on patients with burns has shown that Ps. aeruginosa was removed from a significantly larger proportion (10/24) of burns in patients treated with carbenicillin and probenecid than in untreated controls (1/23). The highest blood levels of carbenicillin (48–64 μg./ml.) were in the same range as its minimal inhibitory concentration against the infecting strains. A strain of Ps. aeruginosa which acquired resistance to carbenicillin in vitro was converted to a small colony form and showed a loss of virulence for burned mice. In a similar experitent with gentamicin the resistant variants were also small colony forms, but retained some virulence for mice. © 1967, British Medical Journal Publishing Group. All rights reserved.