Ototoxicity resulting from combined administration of metronidazole and gentamicin

Hypothesis: The hypothesis that metronidazole can augment the ototoxicity o f gentamicin was tested. ackground: Metronidazole and gentamicin are antibiotics that are used in co mbination to provide broad-spectrum antimicrobial coverage. It has been obs erved clinically that an increased ototoxic effect occurs when these agents are used in combination. Methods: Groups of guinea pigs were given various doses of gentamicin alone , various doses of gentamicin in combination with metronidazole, or metroni dazole alone. Auditory damage was determined electrophysiologically by meas urement of the compound action potential. Hair cell damage was quantified b y immunofluorescent microscopy. Results: Electrophysiologic data revealed an augmented ototoxic effect when metronidazole was given with both a moderate and a high dose of gentamicin . Thresholds (dB SPLp) for the compound action potential(N1) for animals re ceiving a medium dose of gentamicin alone (50 mg/kg) were approxi50-dB SPLp when metronidazole (35 mg/kg) was administered along with the medium-dose gentamicin. Additionally, animals receiving high-dose gentamicin (75 mg/kg) alone demonstrated increased NI thresholds from 85 to 95 when metronidazol e (35 mg/kg) was added to the gentamicin regimen. This effect was evident h istopathologically by increased cochlear hair cell damage. Outer hair cell loss for animals receiving medium-dose gentamicin alone did not differ from that of controls. When metronidazole (35 mg/kg) was combined, however, out er hair cell loss increased to approximately 50%. Conclusions: These data support the clinical observation of augmented ototo xicity in patients receiving combined gentamicin and metronidazole. Caution should be used when administering these two agents together. Clinicians sh ould consider other antibiotic strategies whenever possible.