We thank Banerjee and colleagues for their article which raises awareness of the ototoxic effects of aminoglycosides. We would also like to draw further attention to their vestibular effects.

Gentamicin is well described in the otolaryngology literature for its use in Meniere’s disease to treat vertigo, where its toxicity initially affects the vestibular system, then at higher doses the cochlear resulting in sensorineural deafness.(1) It is delivered locally to the round window by a variety of techniques including transtympanic injections or grommet insertions and gentamicin drops.(2) Dosing regimens are often titrated to effect, where vertigo symptoms are reduced before sensorineural hearing loss is observed.

It is therefore no surprise to see patients previously treated with aminoglycosides attending vestibular clinics. These patients have often received aminoglycoside treatment doses that have complied with locally agreed dosing regimens, yet experienced vestibular toxicity and acute imbalance, without necessarily experiencing sensorineural hearing loss. This suggests that despite their daily doses falling within dosing guidelines, the vestibular toxicity must be attributable to the cumulative dose, as gentamicin may persist in the inner ear for months after cessation of treatment.(3)

Regular medical interview, otoscopy and audiometry as the authors suggest would fail to identify those patients with vestibular toxicity, prior to the onset of sensorineural hearing loss. We commend the use of a simple bedside screen called the dynamic visual acuity test, or oscillopsia test which would help indicate early vestibular failure, enabling clinicians to consider altering therapy preventing further vestibular, or indeed cochlear side effects.(4)

1.Sajjadi H, Paparella MM. Meniere’s disease. Lancet 2008;372:406-14.
2.Pullens B, van Benthem PP. Intratympanic gentamicin for Ménière's disease or syndrome. Cochrane Database of Systematic Reviews 2011,Issue 3.Art. No.: CD008234. DOI: 10.1002/14651858.CD008234.pub2.
3.Schacht J. Mechanisms for Aminoglycoside Ototoxicity: Basic Science Research. In: Roland PS, Rutka JA, eds. Ototoxicity. Hamilton, Ontario: B.C. Decker Inc 2004:93-100.
4.Blakley BW, Barber HO, Tomlinson RD, Stoyanoff S, Mai M. On the Search for Markers of Poor Vestibular Compensation. Otolaryngol Head Neck Surg 1989;101:572-577.

Competing interests: None declared

Both Nick Murch and Sebastian Hendricks raise the issue of idiosyncratic extreme sensitivity to the ototoxic effects of aminoglycosides in those with the mitochondrial m.1555A>G mutation. The mutation is present in 1 in 300 to 1 in 500 people in the general UK population.

However, taking a maternal family history of deafness prior to aminoglycoside administration will not reliably detect those who are at risk of permament deafness due to this mutation. Penetrance is often very low (1). We have shown in two large UK cohort studies that the majority of people with this mutation have hearing that is within normal limits, unless they have been exposed to aminoglycosides (2, 3). As Sebastian Hendricks has pointed out, in those who are likely to receive repeated doses or courses of aminoglycosides, genetic testing is the only way of reliably identifying those at risk of permanent deafness. Testing should be initiated in all patients likely to receive multiple doses, regardless of family history. It is possible that a single dose may be tolerated without effect, but highly unlikely that multiple doses can be given to those with the mutation and for hearing to remain normal.

1: Dai P, Liu X, Han D, Qian Y, Huang D, Yuan H, Li W, Yu F, Zhang R, Lin H, He Y, Yu Y, Sun Q, Qin H, Li R, Zhang X, Kang D, Cao J, Young WY, Guan MX. Extremely low penetrance of deafness associated with the mitochondrial 12S rRNA mutation in 16 Chinese families: implication for early detection and prevention of deafness. Biochem Biophys Res Commun. 2006 Feb 3;340(1):194-9.

2: Rahman S, Ecob R, Costello H,
Sweeney MG, Duncan AJ, Pearce K, Strachan D, Forge A, Davis A, Bitner-Glindzicz M. Hearing in 44-45 year olds with m.1555A>G, a genetic mutation predisposing to aminoglycoside-induced deafness: a population based cohort study. BMJ Open. 2012 Jan 5;2:e000411.

3: Bitner-Glindzicz M, Pembrey M, Duncan A, Heron J, Ring SM, Hall A, Rahman S. Prevalence of mitochondrial 1555A-->G mutation in European children. N Engl J Med. 2009 Feb 5;360(6):640-2.

Competing interests: None declared

Thank you for the interesting summary of a practice that still has high variability between different institutions. I was surprised however that taking a thorough history from the patient or relatives with regards to a family history of premature maternal deafness is not clearly advocated prior to the commencement of aminoglycoside therapy.

A significant proportion of patients who develop aminoglycoside-induced ototoxicity carry mutations in the maternally-inherited mitochondrial DNA, with the commonest predisposing abnormality being m.1555A>G. 1 Patients with these mutations can develop after exposure to a lower cumulative dose of the aminoglycoside, possibly just a single dose, than those not possessing these mutations. 2

Genetic screening prior to commencing aminoglycoside therapy may currently not be cost-effective3 nor practical, however a genetic predisposition to aminoglycoside-induced ototoxicity could be diagnosed by the taking of an accurate and focussed family history. 1

Healthcare professionals need to be made more aware of the potentially-avoidable disastrous consequences of this routine group of antibiotics.

1. Fischel-Ghodsian N, Prezant TR, Chaltrew WE, Wendt KA, Nelson RA, Arnos KS, Falk RE. Mitochondrial gene mutation is a significant predisposing factor in aminoglycoside ototoxicity, AM J Otolaryngol 1997;18(3):173-178

2. Usami S, Abe S, Shinkawa H, Kimberling WJ, Sensorineural hearing loss caused by mitochondrial DNA mutations: special reference to the A1555G mutation, J Commun Disord 1998;31:423-34

3. Bitner-Glindzicz M, Rahman S, Ototoxicity caused by aminoglycosides is severe and permanent in genetically susceptible people, BMJ 2007;335:784-5

Competing interests: None declared