Chemotherapy against Pseudomonas aeruginosa in cystic fibrosis. A study of carbenicillin, azlocillin or piperacillin in combination with tobramycin

Abstract

A comparative study was made on tobramycin combined with either carbenicillin (500 mg/kg/day) or one of the new penicillins: azlocillin or piperacillin (both 300 mg/kg/day) in 50 cystic fibrosis patients with chronic Pseudomonas aeruginosa infection. Average 2-h levels of penicillins in serum were 46 micrograms/ml (piperacillin), 88 micrograms/ml (azlocillin) and 66 micrograms/ml (carbenicillin). The Pseudomonas strains were significantly more sensitive to piperacillin and azlocillin than to carbenicillin (minimal inhibitory concentrations 1.9, 2.3 and 4.2 micrograms/ml). In 21 of 54 treatment course temporary eradication of Pseudomonas was achieved. Improved ventilatory capacity and diminished proteolytic activity in sputum were seen in most patients with or without bacteriological treatment success. Resistant strains - often belonging to other types - appeared in the patients with treatment failure. With increased number of precipitating antibodies against Pseudomonas and with increased minimal inhibitory concentrations, the chance of eradication was smaller. Seven out of 20 treated with azlocillin and 14 out of 30 treated with piperacillin developed fever and exanthema by the end of treatment. Our experience suggests caution in the use of the new penicillins.