Tolerance, pharmacokinetics and efficacy of once daily amikacin for treatment of Pseudomonas aeruginosa pulmonary exacerbations in cystic fibrosis patients

Twenty cystic fibrosis patients aged 1.8-22 years (mean +/- SD: 9.6 +/- 4.8 years) with Pseudomonas aeruginosa pulmonary exacerbations were treated with amikacin (AM) (35 mg/kg/day in one daily 30 min infusion) associated with either ceftazidime (200 mg/kg/day in 3 i.v. injections) (n = 19) or imipenem (n = 1) at the same dose. Glomerular and tubular functions (creatinine clearance, 24-h proteinuria, beta 2 microglobulinuria, lysozymuria) and audiometry remained within normal ranges from day 0 to day 14. A peak concentration of AM of 83 +/- 19 mg/l and a trough concentration of 0.8 +/- 0.5 mg/l were observed in blood while AM levels in sputum were above the minimal inhibitory concentration 50 from 30 min to 16 h. No serum accumulation of AM was observed during the treatment. From day 0 to day 14, the following changes were observed: weight/height ratio: 96%-100% (P < 0.001); daily energy intake: 111%-128% of RDA (P < 0.001); prealbumin: 195-290 mg/l (P < 0.001); forced vital capacity (FVC): 66%-81% (P < 0.01); forced expiratory volume in 1 s: 60%-75% (P < 0.01); forced expiratory flow between 25% and 75% of FVC: 42%-56% (P < 0.01); nocturnal SaO2 also improved significantly; cardiac rate decreased from 89 +/- 18/min to 76 +/- 16/min (P < 0.001); respiratory rate decreased from 31 +/- 15/min to 26 +/- 10/min (P < 0.05); inflammatory parameters (white blood cells, polymorphonuclear cells, erythrocyte sedimentation rate) also improved. Once daily amikacin administration associated with ceftazidime is well tolerated for the treatment of Pseudomonas aeruginosa pulmonary exacerbations in cystic fibrosis patients. Serum peak levels and diffusion in sputum are higher than with a conventional schedule.