Aminoglycoside antibiotics cochleotoxicity in paediatric cystic fibrosis (CF) patients: A study using extended high-frequency audiometry and distortion product otoacoustic emissions

Abstract

Abstract

Despite known ototoxic effects of aminoglycoside (AG) antibiotics, audiological assessment is not routinely undertaken in UK CF patients. Consequently, the incidence of hearing loss is not well established. Objective: To document the incidence of hearing loss in cystic fibrosis (CF) children. Design: Hearing function of 45 children from Great Ormond Street Hospital was assessed using pure-tone audiometry up to 20kHz and DPOAEs up to 8kHz. Study Sample: 39/45 of participants had received intravenous (IV) AGs, 23 of which received repeated IV AGs every 3 months. Results: In this high exposure group, 8 (21%) had clear signs of ototoxicity; average 8-20kHz thresholds were elevated by ∼50dB and DPOAE amplitudes were >10dB lower at f2 3.2-6.3 kHz. The remaining 31/39 (79%) of AG exposed patients had normal, even exceptionally good hearing. The 21% incidence of ototoxicity we observed is substantial and higher than previously reported. However, our finding of normal hearing in children with equal AG exposure strongly suggests that other unknown factors, possibly genetic susceptibility, influence this outcome. Conclusions: We recommend comparable auditory testing in all CF patients with high AG exposures. Genetic analysis may help explain the dichotomy in response to AGs found.

Sumario

A pesar de los conocidos efectos ototóxicos de los antibióticos aminoglucósidos (AG), en el Reino Unido no se lleva a cabo de rutina una evaluación audiológica en los pacientes con fibrosis quística (CF); consecuentemente, la incidencia de hipoacusia no está bien establecida. Objetivo: Documentar la incidencia de trastornos auditivos en niños con fibrosis quística (CF). Diseño: Se evaluó la función auditiva de 45 niños del Hospital Great Ormon Street, usando audiometría de tonos puros hasta 20kHz y DPOAE hasta 8 kHz. Muestra Del Estudio: 39/45 participantes habían recibido AG intravenosos (IV), 23 de los cuáles los recibieron repetidamente por vía IV, cada 3 meses. Resultados: En este grupo de alta exposición, 8 niños (21%) mostraban claros signos de ototoxicidad; los umbrales promedio de 8-20 kHz estaban elevados por ∼50dB y las amplitudes de las DPOAE estaban >10dB más bajas en f2 3.2-6.3 kHz. Los restantes 31/39 (79%) pacientes expuestos a AG tenían una audición normal e incluso, excepcionalmente buena. La incidencia de ototoxicidad del 21% que observamos es sustancial y es más alta de lo previamente reportado. Sin embargo, nuestro hallazgo de audición normal en niños con exposición equivalente a AG sugiere fuertemente que otros factores desconocidos, posiblemente la susceptibilidad genética, influyen en los resultados. Conclusiones: Recomendamos evaluaciones auditivas similares en todos los pacientes con CF con alta exposición a AG. El análisis genético puede ayudar a explicar la dicotomía encontrada en cuanto a la respuesta a AG.

Key Words::

• Cochleotoxicity
• Ototoxicity
• Aminoglycoside antibiotics
• Hearing assessment
• High frequency audiometry
• Distortion-product otoacoustic emissions
• Cystic fibrosis paediatric population

Acknowledgements

The authors are very grateful to the CF children and families who participated in this research, and to staff members of the departments of Respiratory Medicine (CF unit) and Audiology at Great Ormond Street Hospital who assisted in this work. Thanks are due to Deafness Research UK (DRUK) for providing an equipment grant (reference number: 474:uei:ga) in support of this research. Parts of this work have been presented at the 32nd European Cystic Fibrosis Conference, Brest, France, 10–13 June, 2009.

Declaration of interest: The authors report no conflicts of interest. The authors are responsible for the content and writing of the paper.