The present multicenter, randomized crossover study compared the safety and efficacy of continuous infusion with those of short infusions of
ceftazidime in patients with
cystic fibrosis. Patients with chronic Pseudomonas aeruginosa colonization received two successive courses of intravenous
tobramycin and
ceftazidime (200 mg/kg of
body weight/day) for pulmonary exacerbation administered as thrice-daily short infusions or as a continuous infusion. The primary endpoint was the variation in the forced expiratory volume in 1 s (FEV1) during the course of
antibiotic treatment. Sixty-nine of the 70 patients enrolled in the study received at least one course of
antibiotic treatment. The improvement in FEV1 at the end of
therapy was not statistically different between the two treatment procedures (+7.6% after continuous infusion and +5.5% after short infusions) but was better after continuous
ceftazidime treatment in patients harboring resistant isolates (P < 0.05). The interval between the course of
antibiotic treatments was longer after the continuous infusion than after the short infusion of
ceftazidime (P = 0.04). The mean serum
ceftazidime concentration during the continuous infusion was 56.2 +/- 23.2 microg/ml; the mean peak and trough concentrations during the short infusions were 216.3 +/- 71.5 and 12.1 +/- 8.7 microg/ml, respectively. The susceptibility profiles of the P. aeruginosa isolates remained unchanged and were similar for both regimens. Quality-of-life scores were similar whatever the treatment procedure, but 82% of the patients preferred the continuous-infusion regimen. Adverse events were not significantly different between the two regimens. In conclusion, the continuous infusion of
ceftazidime did not increase its toxicity and appeared to be as efficient as short infusions in patients with
cystic fibrosis as a whole, but it gave better results in patients harboring resistant isolates of P. aeruginosa.