Nebulized tobramycin in the treatment of adult CF pulmonary exacerbations.
BACKGROUND
Repeated courses of intravenous (IV) aminoglycosides in cystic fibrosis (CF) patients are associated with cumulative nephrotoxicity. Targeting their delivery through the inhaled route during acute pulmonary exacerbations may also be effective, but without systemic side effects.


METHODS
Using a randomized crossover trial design, in a pilot study we compared 14 days of IV tobramycin with nebulized tobramycin 300 mg twice a day (TNS) in acute respiratory exacerbations in 20 CF adults chronically infected with Pseudomonas aeruginosa (Psa). Patients also received IV colistin in both arms.


RESULTS
Improvement in spirometry was similar between the two groups [mean change in FEV1 % predicted: IV group 16.4 (standard deviation 8.5) versus TNS group 19.9 (11.3), p=0.26], but there was more suppression of sputum Psa in the TNS group [mean difference between treatments 0.85 log10 colony-forming units/mL (CI 0.03 to 1.67), p=0.05]. IV tobramycin was associated with a greater urinary protein leak [mean difference between treatments 0.59 mg/24 hr (0.30 to 0.87), p=0.0005] and higher urinary levels of markers of acute renal tubular injury: N-acetylglucosaminidase [0.72 IU/mmol (0.37 to 1.07), p=0.0004], alanine aminopeptidase [1.19 IU/mmol (0.70 to 1.68), p=0.0001], and β2-microglobulin [0.44 μg/mmol (0.16 to 0.72), p=0.0046] than TNS. Compared with IV tobramycin, TNS treatment prolonged the time to next exacerbation requiring hospitalization (p<0.001). Patient satisfaction was similar with both treatments, and no serious adverse effects were recorded.


CONCLUSIONS
TNS is effective in treating acute exacerbations of Psa in CF patients, but with a renal sparing potential compared with the IV preparation.
1 University Hospital of South Manchester , Wythenshawe, United Kingdom .
Mohamed
M
Al-Aloul
Dilip
D
Nazareth
Martin
M
Walshaw
D000280:Administration, Inhalation; D000293:Adolescent; D000328:Adult; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics; D018592:Cross-Over Studies; D003550:Cystic Fibrosis / Q000175:diagnosis / Q000188:drug therapy* / Q000382:microbiology / Q000503:physiopathology; D018450:Disease Progression; D004739:England; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D007668:Kidney / Q000187:drug effects / Q000503:physiopathology; D008168:Lung / Q000187:drug effects* / Q000382:microbiology / Q000503:physiopathology; D008297:Male; D009330:Nebulizers and Vaporizers; D010865:Pilot Projects; D011552:Pseudomonas Infections / Q000175:diagnosis / Q000188:drug therapy* / Q000382:microbiology / Q000503:physiopathology; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000302:isolation & purification; D012141:Respiratory Tract Infections / Q000175:diagnosis / Q000188:drug therapy* / Q000382:microbiology / Q000503:physiopathology; D013183:Sputum / Q000382:microbiology; D013997:Time Factors; D014031:Tobramycin / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics; D016896:Treatment Outcome; D055815:Young Adult
D000900:Anti-Bacterial Agents; D014031:Tobramycin
cystic fibrosis; nebulized tobramycin; renal sparing