title: Continuous versus intermittent infusions of ceftazidime for treating exacerbation of cystic fibrosis.
abstract: 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.
authors.affiliation: Centre de Ressources et de Compétences pour la Mucoviscidose, Service de Pneumologie, Hôpital Cochin, Assistance Publique des Hôpitaux de Paris, Paris, France. dominique.hubert@cch.aphp.fr
authors.forename: Dominique
authors.initials: D
authors.lastname: Hubert
authors.forename: Evelyne
authors.initials: E
authors.lastname: Le Roux
authors.forename: Thibaud
authors.initials: T
authors.lastname: Lavrut
authors.forename: Benoit
authors.initials: B
authors.lastname: Wallaert
authors.forename: Philippe
authors.initials: P
authors.lastname: Scheid
authors.forename: Dominique
authors.initials: D
authors.lastname: Manach
authors.forename: Dominique
authors.initials: D
authors.lastname: Grenet
authors.forename: Isabelle
authors.initials: I
authors.lastname: Sermet-Gaudelus
authors.forename: Sophie
authors.initials: S
authors.lastname: Ramel
authors.forename: Claire
authors.initials: C
authors.lastname: Cracowski
authors.forename: Anne
authors.initials: A
authors.lastname: Sardet
authors.forename: Nathalie
authors.initials: N
authors.lastname: Wizla
authors.forename: Eric
authors.initials: E
authors.lastname: Deneuville
authors.forename: Rodolphe
authors.initials: R
authors.lastname: Garraffo
mesh_terms: D000293:Adolescent; D000328:Adult; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000009:adverse effects; D002442:Ceftazidime / Q000008:administration & dosage* / Q000009:adverse effects; D018592:Cross-Over Studies; D003550:Cystic Fibrosis / Q000188:drug therapy*; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D002442:Ceftazidime