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Antimicrobial Agents and Chemotherapy, September 2009, p. 3650-3656, Vol. 53, No. 9
0066-4804/09/$08.00+0     doi:10.1128/AAC.00174-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Continuous versus Intermittent Infusions of Ceftazidime for Treating Exacerbation of Cystic Fibrosis{triangledown}

Dominique Hubert,1* Evelyne Le Roux,2 Thibaud Lavrut,3 Benoit Wallaert,4 Philippe Scheid,5 Dominique Manach,1 Dominique Grenet,6 Isabelle Sermet-Gaudelus,7 Sophie Ramel,8 Claire Cracowski,9 Anne Sardet,10 Nathalie Wizla,11 Eric Deneuville,12 and Rodolphe Garraffo3

Centre de Ressources et de Compétences pour la Mucoviscidose, Service de Pneumologie, Hôpital Cochin, Assistance Publique des Hôpitaux de Paris, Paris, France,1 Vaincre la Mucoviscidose, Paris, France,2 Service de Pharmacologie, Centre Hospitalier Universitaire, Nice, France,3 Centre de Ressources et de Compétences pour la Mucoviscidose, Service de Pneumologie, Hôpital Calmette, Lille, France,4 Centre de Ressources et de Compétences pour la Mucoviscidose, Service de Pneumologie, Hôpital de Brabois, Vandoeuvre-les-Nancy, France,5 Centre de Ressources et de Compétences pour la Mucoviscidose, Service de Pneumologie, Hôpital Foch, Suresnes, France,6 Centre de Ressources et de Compétences pour la Mucoviscidose, Service de Pédiatrie, Hôpital Necker, Assistance Publique des Hôpitaux de Paris, Paris, France,7 Centre de Ressources et de Compétences pour la Mucoviscidose, Centre de Perharidy, Roscoff, France,8 Centre de Ressources et de Compétences pour la Mucoviscidose, Centre Hospitalier Universitaire, Grenoble, France,9 Centre de Ressources et de Compétences pour la Mucoviscidose, Service de Pédiatrie, Centre Hospitalier du Dr. Schaffner, Lens, France,10 Centre de Ressources et de Compétences pour la Mucoviscidose, Service de Pédiatrie, Hôpital Jeanne de Flandre, Lille, France,11 Centre de Ressources et de Compétences pour la Mucoviscidose, Service de Pédiatrie, Hôpital Sud, Rennes, France,12

Received 7 February 2009/ Returned for modification 1 April 2009/ Accepted 9 June 2009

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 µg/ml; the mean peak and trough concentrations during the short infusions were 216.3 ± 71.5 and 12.1 ± 8.7 µg/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.

* Corresponding author. Mailing address: CRCM Adultes, Service de Pneumologie, Hôpital Cochin, 27, Rue du Faubourg Saint Jacques, Paris Cedex 14 75679, France. Phone: (33) 1 58 41 23 78. Fax: (33) 1 58 41 23 62. E-mail: dominique.hubert{at}cch.aphp.fr

{triangledown} Published ahead of print on 15 June 2009.

Antimicrobial Agents and Chemotherapy, September 2009, p. 3650-3656, Vol. 53, No. 9
0066-4804/09/$08.00+0     doi:10.1128/AAC.00174-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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