Efficacy of once-daily tobramycin monotherapy for acute pulmonary exacerbations of cystic fibrosis: A preliminary study

• Published in: Pediatric pulmonology 2001-05, Vol.31 (5), p.367-376
• Main Authors: Master, Vahid, Roberts, G.W., Coulthard, K.P., Baghurst, P.A., Martin, A., Roberts, M.E., Onishko, C.R., Martin, A.J., Linke, R.J., Holmes, M., Jarvinen, A., Kennedy, D., Colebatch, K.A., Hansman, D., Parsons, D.W.
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Anti-Bacterial Agents - administration & dosage; Anti-Bacterial Agents - therapeutic use; Antibacterial agents; Antibiotics. Antiinfectious agents. Antiparasitic agents; Biological and medical sciences; Ceftazidime - administration & dosage; Ceftazidime - therapeutic use; Cephalosporins - administration & dosage; Cephalosporins - therapeutic use; Child; cystic fibrosis; Cystic Fibrosis - complications; Cystic Fibrosis - microbiology; Delayed-Action Preparations; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Injections, Intravenous; Male; Medical sciences; once-daily tobramycin monotherapy; Pharmacology. Drug treatments; Pseudomonas aeruginosa; Pseudomonas Infections - drug therapy; Pseudomonas Infections - etiology; Pseudomonas Infections - microbiology; pulmonary exacerbations; Respiratory Function Tests; Respiratory Tract Infections - drug therapy; Respiratory Tract Infections - etiology; Respiratory Tract Infections - microbiology; Time Factors; Tobramycin - administration & dosage; Tobramycin - therapeutic use; Treatment Outcome; Tropical medicine
• ISSN: 8755-6863; 1099-0496
• DOI: 10.1002/ppul.1060

Our objective was to compare the efficacy, safety, and microbiology of once‐daily intravenous (IV) tobramycin with conventional 8‐hourly tobramycin/ceftazidime IV therapy for acute Pseudomonas aeruginosa (PA) pulmonary exacerbations in cystic fibrosis (CF). CF patients with PA‐induced pulmonary exacerbations were allocated to receive either once‐daily tobramycin (Mono) or conventional therapy with tobramycin/ceftazidime given 8‐hourly (Conv). The two longitudinal groups received therapy in a double‐blind, randomized manner over a period of 2 years. Tobramycin doses were adjusted to achieve a daily area under the time‐concentration curve of 100 mg·hr/L in both groups. Results were assessed for both short‐term changes (efficacy and safety after 10 days of IV antibiotics during acute exacerbations) and long‐term changes (efficacy, safety, and sputum microbiology between study entry and exit). Pulmonary function tests (PFTs) on admission were similar in both groups. After 10 days of IV antibiotics, absolute mean improvements in percent of predicted PFTs were 12.8, 12.1, and 13.7 for forced expiratory volume in 1 sec (FEV1), forced vital capacity (FVC), and forced expired flow between 25–75% of FVC (FEF25–75%) in the Conv group (n = 51 admissions( compared to 10.6, 9.9, and 10.6 in the Mono group (n = 47((P