Efficacy, tolerance, and pharmacokinetics of once daily tobramycin for pseudomonas exacerbations in cystic fibrosis
- P Vica,
- S Ategboa,
- D Turcka,
- M O Hussonb,
- V Launaya,
- G A Loeuilled,
- A Sardeta,
- A Deschildrea,
- D Druone,
- C Arrouet-Lagandec
- aDepartment of Paediatrics, Lille University Hospital, Lille, France, bDepartment of Bacteriology, Lille University Hospital, cDepartment of Otorhinolaryngology, Lille University Hospital, dDepartment of Paediatrics, City Hospital, Dunkirk, France, eDepartment of Paediatrics, City Hospital, Camiers, France
- Professor Dominique Turck, Centre de Soins pour la Mucoviscidose, Clinique de Pédiatrie, Hôpital Jeanne de Flandre, 59037 Lille Cédex, France. email:
- Accepted 16 January 1998
OBJECTIVE To compare once daily with thrice daily tobramycin for treatment of Pseudomonas aeruginosainfection in patients with cystic fibrosis.
DESIGN 22 patients with cystic fibrosis, mean (SD) age 11 (3.4) years (range 5.6–19.3), with pulmonary pseudomonas exacerbations were randomly assigned to receive a 14 day course of tobramycin (15 mg/kg/day) either in three infusions (group A) (n = 10) or a single daily infusion (group B) (n = 12), combined with ceftazidime (200 mg/kg/day as three intravenous injections). Efficacy was assessed by comparison of pulmonary, nutritional, and inflammatory indices on days 1 and 14. Cochlear and renal tolerance were assessed on days 1 and 14. Tobramycin concentration was measured in serum and sputum 1, 2, 3, 4, 8, and 24 hours after the start of the infusion. Analysis was by non-parametric Wilcoxon test.
RESULTS Variables improving (p < 0.05) in both groups A and B were, respectively: weight/height (+4% and +3.1%), plasma prealbumin (+66 and +63 mg/l), forced vital capacity (FVC) (+14% and +11%), forced expiratory volume in one second (+15% and +14%), and forced expiratory flow between 25% and 75% of FVC (+13% and +21%). Improvement was not significantly different between groups. Renal and cochlear indices remained within the normal range. Serum peak concentration of tobramycin on day 1 was 13.2 (7.1) mg/l in group A and 42.5 (11.2) mg/l in group B (p < 0.001); serum trough was 1.1 (0.8) mg/l in group A and 0.3 (0.2) mg/l in group B (p < 0.01). Tobramycin concentrations in sputum were two to three times higher in group B than group A.
CONCLUSIONS Once daily tobramycin combined with three injections of ceftazidime is safe and effective for the treatment of pseudomonas exacerbations in cystic fibrosis patients.