Related Experiment Videos
Ototoxicity resulting from combined administration of metronidazole and gentamicin
L C Riggs1, W P Shofner, A R Shah
1Department of Otolaryngology, Loyola University Medical Center, Maywood, Illinois 60153, USA.
Hypothesis:
The hypothesis that metronidazole can augment the ototoxicity of gentamicin was tested.
Background:
Metronidazole and gentamicin are antibiotics that are used in combination to provide broad-spectrum antimicrobial coverage. It has been observed 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 metronidazole alone. Auditory damage was determined electrophysiologically by measurement of the compound action potential. Hair cell damage was quantified by 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 receiving a medium dose of gentamicin alone (50 mg/kg) were approximately 20-dB SPLp. This threshold increased to approximately 50-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 N1 thresholds from 85 to 95 when metronidazole (35 mg/kg) was added to the gentamicin regimen. This effect was evident histopathologically 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, outer hair cell loss increased to approximately 50%.
Conclusions:
These data support the clinical observation of augmented ototoxicity in patients receiving combined gentamicin and metronidazole. Caution should be used when administering these two agents together. Clinicians should consider other antibiotic strategies whenever possible.
Insights
Combining metronidazole with gentamicin antibiotics increases the risk of ototoxicity, causing significant auditory and hair cell damage. Caution is advised when using these drugs together.
Area of Science:
- Ototoxicology
- Pharmacology
- Auditory Neuroscience
Background:
- Metronidazole and gentamicin are broad-spectrum antibiotics often used in combination.
- Clinical observations suggest increased ototoxicity when these antibiotics are co-administered.
Purpose of the Study:
- To investigate the hypothesis that metronidazole augments the ototoxicity of gentamicin.
- To quantify the combined ototoxic effects of metronidazole and gentamicin.
Main Methods:
- Guinea pigs were administered varying doses of gentamicin alone, gentamicin with metronidazole, or metronidazole alone.
- Auditory damage was assessed using electrophysiological measurements of compound action potential (CAP).
- Cochlear hair cell damage was quantified via immunofluorescent microscopy.
Main Results:
- Electrophysiological data showed augmented ototoxicity with combined metronidazole and moderate/high-dose gentamicin.
- CAP thresholds increased significantly (e.g., from ~20 to ~50 dB SPLp with medium-dose gentamicin).
- Histopathology revealed increased outer hair cell loss (up to ~50%) when metronidazole was combined with gentamicin.
Conclusions:
- The study supports clinical observations of enhanced ototoxicity from combined gentamicin and metronidazole.
- Clinicians should exercise caution and consider alternative antibiotic regimens when possible.
- This research highlights potential risks associated with co-prescribing these antibiotics.