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Antimicrobial Agents and Chemotherapy, July 2006, p. 2293-2299, Vol. 50, No. 7
0066-4804/06/$08.00+0     doi:10.1128/AAC.00995-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Absence of Cochleotoxicity Measured by Standard and High-Frequency Pure Tone Audiometry in a Trial of Once- versus Three-Times-Daily Tobramycin in Cystic Fibrosis Patients

Michael Mulheran,1* Pauline Hyman-Taylor,2 Kelvin H.-V. Tan,3,{dagger} Sarah Lewis,2 David Stableforth,4 Alan Knox,2 and Alan Smyth3

MRC Centre for Mechanisms of Human Toxicity, University of Leicester, Leicester LE1 9HN, United Kingdom,1 Division of Respiratory Medicine, University of Nottingham, Nottingham NG5 1PB, United Kingdom,2 Department of Child Health, University of Nottingham, and Department of Paediatrics, Nottingham City Hospital, Nottingham NG5 1PB, United Kingdom,3 Department of Respiratory Medicine, Birmingham Heartlands Hospital Birmingham B9 5SS, United Kingdom4

Received 9 August 2005/ Returned for modification 11 December 2005/ Accepted 12 April 2006

We undertook assessment of hearing in patients with cystic fibrosis who were taking part in a large randomized controlled trial of once- versus three-times-daily tobramycin for pulmonary exacerbations of cystic fibrosis (the TOPIC study). All patients were eligible to have standard pure tone audiometry performed across the frequency range of 0.25 to 8 kHz. High-frequency pure tone audiometry over 10 to 16 kHz was also performed with a subset of patients. Audiometry was undertaken at the start of tobramycin treatment, at the end of a 14-day course of treatment, and at follow-up 6 to 8 weeks later. We enrolled 244 patients, of whom 219 (125 children and 94 adults) completed treatment. Nineteen patients were excluded from analysis due to abnormal baseline audiometry. Complete pre- and posttreatment standard audiological data were obtained for 168/219 patients. We found no significant differences in hearing thresholds when they were assessed at the baseline, at the end of treatment, and at follow-up 6 to 8 weeks later were compared. In addition, no significant differences in hearing thresholds were detected between treatment regimens. Similar results were obtained for the subset of 63/168 patients who underwent high-frequency audiometry. We conclude that for a single 14-day course of tobramycin treatment in patients with cystic fibrosis with no preexisiting auditory deficit, no measurable effect on hearing was apparent with either once- or three-times-daily treatment. Estimation of the cumulative cochleotoxic risk in cystic fibrosis patients due to repeated aminoglycoside therapy, as evidenced by the patients excluded from this study due to hearing loss, also requires further characterization.

* Corresponding author. Mailing address: MRC Centre for the Study of Mechanisms of Human Toxicity, Neurotoxicology, Lancaster Road, University of Leicester, Leicester LE1 9HN, United Kingdom. Phone: 44 116 252 5170. Fax: 44 116 252 5616. E-mail: mm22{at}leicester.ac.uk.

{dagger} Present address: GlaxoSmithKline Respiratory Medicines Development Centre, GlaxoSmithKline, Greenford UB6 ONN, United Kingdom.

Antimicrobial Agents and Chemotherapy, July 2006, p. 2293-2299, Vol. 50, No. 7
0066-4804/06/$08.00+0     doi:10.1128/AAC.00995-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.





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