Arch Dis Child 1998;78:536-539 ( June )

Efficacy, tolerance, and pharmacokinetics of once daily tobramycin for pseudomonas exacerbations in cystic fibrosis

P Vic,^a S Ategbo,^a D Turck,^a M O Husson,^b V Launay,^a G A Loeuille,^d A Sardet,^a A Deschildre,^a D Druon,^e C Arrouet-Lagande^c

^a Department of Paediatrics, Lille University Hospital, Lille, France, ^b Department of Bacteriology, Lille University Hospital, ^c Department of Otorhinolaryngology, Lille University Hospital, ^d Department of Paediatrics, City Hospital, Dunkirk, France, ^e Department of Paediatrics, City Hospital, Camiers, France

Correspondence to: Professor Dominique Turck, Centre de Soins pour la Mucoviscidose, Clinique de Pédiatrie, Hôpital Jeanne de Flandre, 59037 Lille Cédex, France. email: dturck{at}chru-lille.fr

Accepted 16 January 1998

OBJECTIVETo compare once daily with thrice daily tobramycin for treatment of Pseudomonas aeruginosa infection in patients with cystic fibrosis.
DESIGN22 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.
RESULTSVariables 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.
CONCLUSIONSOnce daily tobramycin combined with three injections of ceftazidime is safe and effective for the treatment of pseudomonas exacerbations in cystic fibrosis patients.

Keywords: cystic fibrosis; antibiotics; aminoglycosides; Pseudomonas aeruginosa

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© 1998 by Archives of Disease in Childhood
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