Serum and sputum concentrations of azlocillin, cefoperazone and ceftazidime in patients with cystic fibrosis.

Single-dose pharmacokinetics of azlocillin, cefoperazone and ceftazidime were studied in 17 patients with cystic fibrosis (CF). All patients had broncho-pulmonary infections caused by Pseudomonas aeruginosa. Three groups of five, six, and six patients were treated with azlocillin, cefoperazone, or ceftazidime, respectively. The size of the single dose was 133 mg/kg for azlocillin, 66.7 mg/kg for ceftazidime and 66.7 mg/kg for cefoperazone. The clearance values for the three antibiotics calculated from the single-dose data were, on the average, higher than the values previously reported for normal subjects. After the first dose, the patients received a repeated-dose treatment with the same antibiotic. During the first 5 days of therapy, a complement postural drainage of sputum was obtained four times a day for each patient. Cefoperazone could be measured in 47 (39.2%) of the 120 sputum samples assayed while ceftazidime was shown to be present in all 120 sputum samples examined. Azlocillin was not detected in any of the 100 sputum samples assayed.

Alternative antibiotics for the treatment of Pseudomonas infections in cystic fibrosis.

We have investigated the effectiveness of seven new beta-lactam antibiotics, azlocillin, piperacillin, ceftazidime, cefsulodin, cefoperazone, latamoxef (moxalactam), and cefotaxime, against acute pulmonary exacerbations caused by Pseudomonas aeruginosa in cystic fibrosis. Three hundred and fifty-five strains of Ps aeruginosa isolated from 310 sputum cultures (190 cystic fibrosis patients) were tested for susceptibility to the drugs by determination of minimal inhibitory concentrations (MIC). The highest activity was shown by ceftazidime (6% resistant strains) followed by cefsulodin and piperacillin (15 and 16% resistant strains); very low activity was found for cefotaxime and latamoxef (moxalactam). Ceftazidime was the most active drug against 32 pseudomonas isolates that were resistant to both carbenicillin and aminoglycosides (78% susceptible). A randomized, double-blind trial of azlocillin, piperacillin, ceftazidime, cefsulodin or cefoperazone was performed in 111 cystic fibrosis patients with predominant and susceptible pseudomonas in their sputum. Results were evaluated by a clinical, radiological and bacteriological scoring system: the best results were obtained with ceftazidime, followed by cefsulodin and piperacillin. However, pseudomonas was eradicated in only 22 (23%) of the cases with the most active drugs and persisted or reappeared in all the cases 1 to 3 months later. Ceftazidime always eradicated Staph. aureus and Haemophilus influenzae associated with pseudomonas. Similar eradication occurred nearly always with cefsulodin but rarely with the other drugs. No serious drug reaction occurred but a later fever and rash with piperacillin, transient diarrhoea with cefoperazone, vomiting with cefsulodin, and very frequent eosinophilia with ceftazidime should be mentioned. These five drugs offer, in varying degree, alternatives to traditional anti pseudomonas antibiotics in cystic fibrosis pulmonary infections, but they should be used only against well-proven resistant strains. Ceftazidime is best and cefotaxime and latamoxef (moxalactam) least useful.