Ceftazidime in treatment of acute pulmonary exacerbations in patients with cystic fibrosis

Abstract

The pharmacokinetics and clinical efficacy of ceftazidime, a cephalosporin with activity against Pseudomonas aeruginosa, were studied in children with cystic fibrosis. Ceftazidime had high in vitro activity against P. aeruginosa strains isolated from our patients, with a mean MIC90 of 8 micrograms/ml. The first dose of 50 mg/kg IV of ceftazidime achieved serum concentrations of 40.8 +/- 19.7 micrograms/ml at one hour and 3.8 +/- 1 micrograms/ml at four hours after administration (mean values +/- SD). The MIC90 was exceeded by serum concentrations for up to three hours. The elimination of the drug from the blood followed a biexponential decay with an elimination half-life of 60.4 +/- 6.8 min and a total body clearance of 6.0 +/- 3.1 ml/min/kg. Renal clearance of the drug accounted for 75% of the total clearance; these are higher values than those reported for adults. Peak concentrations of ceftazidime in the sputum two hours after a single administration were 4.13 +/- 2.06 micrograms/ml; after seven and 14 days of treatment, sputum concentrations were significantly lower. Eleven children with acute pulmonary exacerbation were treated for 14 days with ceftazidime at a dose of 150 mg/kg/day (12 treatment courses). Significant clinical and radiologic improvements were obtained in nine of 12 patients. In six of 11 cases the P. aeruginosa count decreased by 10(4) CFU/ml. Ceftazidime was well tolerated, and no side effects appeared during treatment.