EFFICACY, TOLERANCE, AND PHARMACOKINETICS OF ONCE-DAILY TOBRAMYCIN FOR PSEUDOMONAS EXACERBATIONS IN CYSTIC-FIBROSIS

Objective-To compare once daily with thrice daily tobramycin for treat ment of Pseudomonas aeruginosa infection in patients with cystic fibro sis. Design-22 patients with cystic fibrosis, mean (SD) age 11 (3.4) y ears (range 5.6-19.3), with pulmonary pseudomonas exacerbations were r andomly assigned to receive a 14 day course of tobramycin (15 mg/kg/da y) either in three infusions (group A) (n = 10) or a single daily infu sion (group B) (n = 12), combined with ceftazidime (200 mg/kg/day as t hree intravenous injections). Efficacy was assessed by comparison of p ulmonary, nutritional, and inflammatory indices on days 1 and 14. Coch lear and renal tolerance were assessed on days 1 and 14. Tobramycin co ncentration was measured in serum and sputum 1, 2, 3, 4, 8, and 24 hou rs after the start of the infusion. Analysis was by non-parametric Wil coxon test. Results-Variables improving (p < 0.05) in both groups A an d B were, respectively: weight/height (+4% and +3.1%), plasma prealbum in (+66 and +63 mg/l), forced vital capacity (FVC) (+14% and +11%), fo rced expiratory volume in one second (+15% and +14%), and forced expir atory flow between 25% and 75% of FVC (+13% and +21%). Improvement was not significantly different between groups. Renal and cochlear indice s remained within the normal range. Serum peak concentration of tobram ycin on day 1 was 13.2 (7.1) mg/l in group A and 42.5 (11.2) mg/l in g roup 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-O nce daily tobramycin combined with three injections of ceftazidime is safe and effective for the treatment of pseudomonas exacerbations in c ystic fibrosis patients.