What are the indications and potential neurological side effects of metronidazole in dogs at standard doses?

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Metronidazole is indicated in dogs for infections caused by obligate anaerobic bacteria, microaerophilic organisms (specifically Campylobacter fetus), and protozoal pathogens including Giardia and Trichomonas. It is not active against facultative anaerobes or obligate aerobes.11 It is also commonly prescribed for Clostridium perfringens-associated disease and has been used in chronic enteropathy, though the evidence base for anti-inflammatory activity in dogs is equivocal.27 Neurological toxicity is the most clinically significant adverse effect at standard doses. Reported signs include disorientation, head tilt, pathologic nystagmus, intentional tremors, forelimb and hindlimb extensor rigidity, spastic paresis, hypermetria, ataxia, nonambulatory status, and seizures.1 Brainstem and cerebellar deficits predominate in dogs.1 Neurotoxicity has been documented at a median dose of 21 mg/kg q12h (range 13–56 mg/kg q12h), with median clinical resolution 3 days after discontinuation (range 1–26 days).5 Caution is warranted at doses exceeding 40 mg/kg/day for any duration.15 Individual sensitivity varies, and neurotoxicity cannot be predicted by dose alone. Serious neurological signs have been reported even at doses below the 60 mg/kg/day threshold historically cited as the toxicity threshold.25 Dogs with hepatic dysfunction are at elevated risk due to prolonged drug elimination, and metronidazole is not advocated for hepatic encephalopathy management in the context of hepatic dysfunction for this reason.36 MRI findings, when present, characteristically affect the dentate nucleus of the cerebellum, and may also involve the interpositus and fastigial nuclei; however, negative MRI does not exclude the diagnosis.1 In humans, resolution of MRI lesions occurs 3–16 weeks after drug discontinuation.1 Beyond neurotoxicity, metronidazole at 25 mg/kg PO q12h causes olfactory degradation in approximately 50% of dogs (9 of 18 dogs showed degraded detection threshold for one or more odo