Central Nervous System Toxicity Associated with Metronidazole Therapy

Kusumi, Rodney K.; Plouffe, Joseph F.; Wyatt, Robert H.; Fass, Robert J.

doi:10.7326/0003-4819-93-1-59

Cited by 103 publications

(55 citation statements)

References 3 publications

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“…Nevertheless, while HPLC can be beneficial for monitoring the drug concentrations in the intoxicated dogs, it is not sufficient to establish the final diagnosis without further investigations. In humans, some studies have shown that neurotoxicity does not seem to correlate with MTZ concentrations in the serum or CSF but further studies in veterinary medicine are warranted (Kusumi et al 1980;Dow et al 1989;Wright and Tyler 2003).…”

Section: Discussionmentioning

confidence: 99%

Toxic encephalopathy associated with high-dose metronidazole therapy in a dog: a case report

Hájek¹,

Šimerdová²,

Vávra³

et al. 2017

Vet. Med. - Czech

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This case report describes an episode of acute ataxia, tremor, vertical nystagmus and progressive weakness in a mixed breed dog treated with high doses of metronidazole. Complete blood cell count, serum biochemistry, coagulation profile, blood pressure measurement, urinalysis, computed tomography of the brain and cerebrospinal fluid examination were unremarkable. Metronidazole had been administered at a dose of 65 mg/ kg/day and neurotoxicity was, therefore, suspected. Drug concentrations in the patient's serum and cerebrospinal fluid were measured using high-performance liquid chromatography and compared to control dogs. Metronidazole administration was immediately discontinued; supportive care consisted of fluid therapy and diazepam treatment. The neurological status of the patient improved rapidly within 72 h. The aim of this case report is to describe the clinical presentation of metronidazole intoxication in a mixed breed dog and to interpret the chromatographic analysis which can be a beneficial diagnostic and screening tool in dogs intoxicated with metronidazole.Keywords: vestibular diseases; cerebellar dysfunction; canine diseases; gamma-aminobutyric acid; chromatography Metronidazole (MTZ) is an injectable and oral synthetic, nitroimidazole antibacterial and antiprotozoal agent. It is commonly used in veterinary practice to treat a wide variety of conditions (Watson 1980;Tams 1984;Happonen et al. 2000;Olson et al. 2005;Cattin et al. 2008;Jergens et al. 2010;Senhorinho et al. 2012). The mode of action requires strict anaerobic conditions; susceptible infectious agents include Bacteroides sp., Clostridium sp., Giardia sp. etc. (Rossignol et al. 1984;Even et al. 1998; Plumb 1999;Marks and Kather 2003;Hausen et al. 2011). MTZ is primarily metabolised in the liver and crosses the blood-brain barrier rapidly; in mice, the unaltered drug accumulates in the cerebellum and hippocampal areas (Plumb 1999;Olson et al. 2005). The recommended dosage for long-term treatment in dogs is 10 mg/kg p.o. twice or three times a day (Plumb 1999). Adverse effects include neurological disorders, lethargy, weakness, neutropenia, hepatotoxicity, haematuria, nausea, vomiting and diarrhoea (Plumb 1999;Weiss 2005). MTZ toxicity can develop suddenly and if unrecognised, can lead to rapid deterioration and death (Wright and Tyler 2003). In cases of acute toxicity from a chronic overdose in dogs, the drug should be discontinued and the patients treated supportively and symptomatically (Wright and Tyler 2003). The aim of this case report is to describe a metronidazole-induced neurotoxicity with subsequent chromatographic analysis in a dog. Case descriptionA six and a half-year-old 7.2-kg uncastrated male mixed breed dog was presented for neurological exSupported by the Ministry of Education, Youth and Sports of the Czech Republic (Institutional research development).

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Section: Discussionmentioning

confidence: 99%

Toxic encephalopathy associated with high-dose metronidazole therapy in a dog: a case report

Hájek¹,

Šimerdová²,

Vávra³

et al. 2017

Vet. Med. - Czech

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“…[4][5][6][7] Patients usually present with cerebellar dysarthria and ataxia that may occasionally fluctuate, as in our first patient. The duration of treatment with metronidazole before cerebellar symptoms manifest is variable, ranging from 28 days 6 to 3 months, 7 and cumulative doses range from 25 g (as in our second patient) to 90 g. 7 Patients usually experience complete resolution of the symptoms after discontinuation of metronidazole, sometimes within a few days.…”

Section: Discussionmentioning

confidence: 99%

“…Proposed mechanisms include binding of metronidazole to RNA, DNA and inhibitory neurotransmitters, as well as inducing both vasogenic and cytotoxic edema. 6 Metronidazole is structurally similar to the thiazole precursor of thiamine and could thereby lead to a reduction in thiamine absorption by acting as a thiamine analog. 9 The propensity to develop these adverse effects is poorly understood.…”

Section: Discussionmentioning

confidence: 99%

Reversible cerebellar syndrome caused by metronidazole

Sarna¹,

Brownell²,

Furtado³

2009

Canadian Medical Association Journal

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“…Nausea occurs in 5 to 15% of patients given standard multiday courses (135,151). In addition, pancreatitis, central nervous system toxicity at high doses (144,212), and transient, reversible neutropenia have been attributed to metronidazole (147). Patients should be warned to avoid alcohol while taking metronidazole.…”

Section: Classes Of Agents and Clinical Propertiesmentioning

confidence: 99%

Treatment of Giardiasis

2001

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Giardia lamblia is both the most common intestinal parasite in the United States and a frequent cause of diarrheal illness throughout the world. In spite of its recognition as an important human pathogen, there have been relatively few agents used in therapy. This paper discusses each class of drugs used in treatment, along with their mechanism of action, in vitro and clinical efficacy, and side effects and contraindications. Recommendations are made for the preferred treatment in different clinical situations. The greatest clinical experience is with the nitroimidazole drugs, i.e., metronidazole, tinidazole, and ornidazole, which are highly effective. A 5- to 7-day course of metronidazole can be expected to cure over 90% of individuals, and a single dose of tinidazole or ornidazole will cure a similar number. Quinacrine, which is no longer produced in the United States, has excellent efficacy but may be poorly tolerated, especially in children. Furazolidone is an effective alternative but must be administered four times a day for 7 to 10 days. Paromomycin may be used during early pregnancy, because it is not systematically absorbed, but it is not always effective. Patients who have resistant infection can usually be cured by a prolonged course of treatment with a combination of a nitroimidazole with quinacrine

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Central Nervous System Toxicity Associated with Metronidazole Therapy

Cited by 103 publications

References 3 publications

Toxic encephalopathy associated with high-dose metronidazole therapy in a dog: a case report

Toxic encephalopathy associated with high-dose metronidazole therapy in a dog: a case report

Reversible cerebellar syndrome caused by metronidazole

Treatment of Giardiasis

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