Sudden sensorineural hearing loss secondary to metronidazole ototoxicity

A 30-year-old Indian gentleman presented to the emergency department of the Royal Victorian Eye and Ear Hospital, Melbourne, with a history of bilateral profound deafness, tinnitus and headache associated with upper- and lower-limb paraesthesia and myalgia. He had been taking metronidazole (400 mg tds) and amoxycillin (500 mg tds) over the preceding 4 days to treat gingivitis. Further questioning revealed that his maternal uncle had experienced identical symptoms while taking metronidazole. Consequently, his metronidazole was immediately discontinued.

After 2 days, he was able to hear faint sounds, and audiography revealed a symmetrical moderate-to-profound sensorineural hearing loss (SNHL) (Box, A). As per our hospital protocol for SNHL management, oral prednisolone was administered (50 mg daily), followed by a slow wean over 3 weeks.

After 8 days, subjective hearing and paraesthesia had improved, and his headache had abated. Audiometry indicated moderate SNHL up to 2000 Hz, with persisting severe high-frequency SNHL (Box, B).

At 6 weeks, repeat audiogram indicated that hearing was normal up to 2000 Hz, but severe-to-profound high-frequency SNHL persisted (Box, C).

Metronidazole is a nitroimidazole antibiotic widely used in various medical specialties. Common side effects include nausea, diarrhoea and abdominal discomfort. Patients receiving high or intravenous doses may experience neurotoxicity, but it is uncommon to suffer ototoxicity.

The first documented case of metronidazole-induced ototoxicity was reported in 1984.1 Since then there have been infrequent but typical reports of SNHL associated with metronidazole. In 1999, two cases of SNHL following about 2 days of treatment with metronidazole for dental sepsis were described.2 More recently, sudden bilateral SNHL after 4 days of metronidazole treatment for diarrhoea has been reported.3

We can only speculate about the mechanism of metronidazole-induced ototoxicity. The clear familial link in our case suggests a potential genetic susceptibility, similar with other ototoxic agents, such as susceptibility for the ototoxic effects of aminoglycosides associated with the mitochondrial A1555G deletion.

Several neurotoxic effects of metronidazole have been hypothesised, including toxic excitation of NMDA receptors leading to production of free radicals and cell death, as well as effects on GABAergic transmission and direct RNA-binding effects.4 Whether or not there is a genetic susceptibility for its effects has not yet been investigated, but it is reported that the onset of neurotoxicity is more rapid and occurs at lower doses in patients of Indian descent than in those of European origin.5

In conclusion, metronidazole is a known neurotoxic antibiotic that can be ototoxic, if only rarely. These adverse effects are reversible after withdrawing the drug. Given its widespread use, it is important that prescribers are aware of these severe adverse reactions.

 

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A: Initial audiogram, showing profound bilateral sensorineural deafness. B: Audiogram, 8 days after cessation of metronidazole, showing improvement in pure tone audiometry at frequencies up to 2000 Hz. C: Audiogram, 6 weeks after cessation of metronidazole, showing near-normal hearing at frequencies up to 2000 Hz, with severe high-frequency hearing loss.