Continuous Versus Short Infusions of Ceftazidime in Cystic Fibrosis

Condition(s) targeted: Cystic Fibrosis; Pseudomonas Aeruginosa; Pulmonary Exacerbation

Intervention: ceftazidime (Drug)

Phase: Phase 4

Status: Terminated

Sponsored by: Association Nationale pour le Traitement à Domicile de l'Insuffisance Respiratoire

Official(s) and/or principal investigator(s):
Dominique Hubert, MD, Principal Investigator, Affiliation: AP-HP

The aim of this trial was to compare the safety and efficacy of courses of tobramycin and ceftazidime, administered intravenously as either thrice daily short infusions or 24 h continuous infusion, in cystic fibrosis patients with acute exacerbation of chronic pulmonary PA infection. In conventional treatment regimens, ceftazidime is administered in the form of thrice daily short infusions, but pharmacodynamic considerations suggest that continuous infusion could be more effective.

Study design: Treatment, Randomized, Open Label, Active Control, Crossover Assignment, Safety/Efficacy Study

Primary outcome: Change in forced expiratory volume in 1s (FEV1) between the beginning and the end of the IV antibiotic course, expressed as a percentage of the predicted normal value

Secondary outcome:

the interval between 2 successive IV antibiotic courses

quality of life scores

sputum collected at the beginning and the end of each antibiotic course

plasma ceftazidime concentration at steady state (Css) for ceftazidime continuous infusion, and before (C trough), 30 minutes (Cmax) and 4 hours after (C4) the beginning of ceftazidime short infusion

C-reactive protein, leukocytes and hepatic enzymes levels at the beginning and the end of each IV antibiotic course

Detailed description: Each patient received two successive IV antibiotic courses during a period of pulmonary exacerbation. One of these courses was delivered as thrice daily 30-minute infusions of ceftazidime in 100 ml of 0. 9% sodium chloride, and the other was delivered as a continuous infusion of ceftazidime in 230 ml of 0. 9% sodium chloride, over 23 hours. The daily dose of ceftazidime was 200 mg/kg, with a maximum dose of 12 g. For ceftazidime continuous infusion, a loading dose of 60 mg/kg (maximum 2 g) was used. All patients also received tobramycin (10 mg/kg), in the form of one 30-minute infusion per day. Portable devices were used: Intermate® SV 200 (Baxter) for the 30-minute short infusions of ceftazidime and tobramycin, Infusor® LV10 (Baxter) for continuous infusion of ceftazidime.

Minimum age: 8 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

- patients with cystic fibrosis older than 8 years

- with chronic Pseudomonas aeruginosa infection of the respiratory tract

- with at least 2 courses of IV antibiotic in the year before enrolment

- at the time of a pulmonary exacerbation

Exclusion Criteria:

- allergy to ceftazidime or tobramycin

- bronchial colonization with Burkholderia cepacia

- renal impairment

- history of lung transplantation

Assistance Publique des Hopitaux de Paris, Hopital Necker, Paris 75015, France

Assistance Publique des Hopitaux de Paris, Hopital Cochin, Paris 75014, France

Assistance Publique des hopitaux de paris, Hopital Trousseau, Paris 75012, France

Assistance Publique des Hopitaux de Paris, Hopital Robert Debré, Paris 75019, France

Hopital Albert Calmette, Lille 59000, France

Hopital de Brabois, Vandoeuvre-les-Nancy 54511, France

Hopital Foch, Suresnes 92150, France

Centre Héliomarin, Roscoff 29684, France

Centre hospitalier Dr Schaffner, Lens 62307, France

Hopital Sud, Rennes 35056, France

CHU Grenoble, Grenoble 38043, France

Hopital Jeanne de Flandre, Lille 59000, France

Hopital Hautepierre, Strasbourg 67000, France

Hopital Larrey, Toulouse 31000, France

Hopital Sainte Marguerite, Marseille 13000, France

Starting date: October 2001
Ending date: April 2004
Last updated: June 2, 2006