Metronidazole-induced encephalopathy: a systematic review

Sørensen, Caspar Godthaab; Karlsson, William Kristian; Amin, Faisal Mohammad; Lindelof, Mette

doi:10.1007/s00415-018-9147-6

Cited by 94 publications

(126 citation statements)

References 121 publications

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“…Our analysis showed no effects on survival or reproductive health after 36 days of MTZ at 0.1 or 1 mM. However, rare reports of neurotoxic effects in patients 31 and infertility post-MTZ in rats 30 suggest endogenous prodrug converting activities may be an issue for certain cell types. To date, studies of MTZ effects in zebrafish have been limited.…”

Section: Discussioncontrasting

confidence: 53%

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NTR 2.0: a rationally-engineered prodrug converting enzyme with substantially enhanced efficacy for targeted cell ablation

Sharrock

Mulligan

Hall

et al. 2020

Preprint

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Heterologously-expressed bacterial nitroreductase (NTR) enzymes sensitize eukaryotic cells to prodrugs such as metronidazole (MTZ), enabling selective cell ablation paradigms that have expanded studies of cell function and regeneration in vertebrate systems. However, first-generation NTRs require confoundingly toxic prodrug treatments (e.g. 10 mM MTZ) and some cell types have proven resistant. We used rational engineering and cross-species screening to develop a NTR variant, NTR 2.0, which exhibits ~100-fold improvement in MTZ-mediated cell-specific ablation efficacy. Toxicity tests in zebrafish showed no deleterious effects of prolonged MTZ treatments of ≤1 mM. NTR 2.0 therefore enables sustained cell loss paradigms and ablation of previously resistant cell types. These properties permit enhanced interrogations of cell function, extended challenges to the regenerative capacities of discrete stem cell niches, and enable modeling of chronic degenerative diseases. Accordingly, we have created a series of bipartite transgenic resources to facilitate dissemination of NTR 2.0 to the research community.

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Section: Discussioncontrasting

confidence: 53%

“…Long-term MTZ exposure has been implicated in rodent male infertility 30 and associated (rarely) with neurotoxic effects in patients 31 . Therefore, we assessed fecundity, fertility, and offspring survival rates of fish exposed to 1, 0.1, or 0 mM MTZ once they reached sexual maturity (~3 months of age).…”

Section: Prolonged Low Dose Mtz Exposures In Zebrafishmentioning

confidence: 99%

NTR 2.0: a rationally-engineered prodrug converting enzyme with substantially enhanced efficacy for targeted cell ablation

Sharrock

Mulligan

Hall

et al. 2020

Preprint

View full text Add to dashboard Cite

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“…Even if the exact active substance was not traceable, a therapy with metronidazole seems to be very likely. Metronidazole-induced encephalopathies described in the literature differ in their typical clinical course from our case [14]. Nevertheless, we cannot exclude such a possible or other (unknown) drug side effect as the cause of the persistent impaired consciousness in the retrospective assessment of the case.…”

Section: Discussionmentioning

confidence: 54%

Travel-associated neurological disease terminated in a postmortem diagnosed atypical HSV-1 encephalitis after high-dose steroid therapy – a case report

Osterman

Ruf²,

Domingo

et al. 2020

BMC Infect Dis

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Background: Human encephalitis can originate from a variety of different aetiologies, of which infection is the most common one. The diagnostic work-up is specifically challenging in patients with travel history since a broader spectrum of unfamiliar additional infectious agents, e. g. tropical disease pathogens, needs to be considered. Here we present a case of encephalitis of unclear aetiology in a female traveller returning from Africa, who in addition developed an atypical herpes simplex virus (HSV) encephalitis in close temporal relation with high-dose steroid treatment. Case presentation: A previously healthy 48-year-old female presented with confusion syndrome and impaired vigilance which had developed during a six-day trip to The Gambia. The condition rapidly worsened to a comatose state. Extensive search for infectious agents including a variety of tropical disease pathogens was unsuccessful. As encephalitic signs persisted despite of calculated antimicrobial and antiviral therapy, high-dose corticosteroids were applied intravenously based on the working diagnosis of an autoimmune encephalitis. The treatment did, however, not improve the patient's condition. Four days later, bihemispheric signal amplification in the insular and frontobasal cortex was observed on magnetic resonance imaging (MRI). The intracranial pressure rapidly increased and could not be controlled by conservative treatment. The patient died due to tonsillar herniation 21 days after onset of symptoms. Histological examination of postmortem brain tissue demonstrated a generalized lymphocytic meningoencephalitis. Immunohistochemical reactions against HSV-1/2 indicated an atypical manifestation of herpesviral encephalitis in brain tissue. Moreover, HSV-1 DNA was detected by a next-generation sequencing (NGS) metagenomics approach. Retrospective analysis of cerebrospinal fluid (CSF) and serum samples revealed HSV-1 DNA only in specimens one day ante mortem.

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“…1 Although rarely, its use in both long-term and short-term has been reported to be associated with neurotoxicity including polyneuropathy, altered mental status, cerebellar dysfunction, visual impairment, seizures, and encephalopathy. 2,3 Characteristic magnetic resonance imaging (MRI) findings have been reported in metronidazole-induced encephalopathy, such as symmetrical T2-weighted and fluid-attenuated inverse recovery (FLAIR) hyperintensities, of cerebellar dentate nuclei, splenium of corpus callosum, midbrain, pons, medulla, and cerebral white matter in order of decreasing frequency. Diffusion-weighted images-apparent diffusion coefficient (DWI-ADC) may have a role in diagnosis and in prediction of the prognosis.…”

Section: Introductionmentioning

confidence: 99%

Pediatric Metronidazole-Induced Encephalopathy: A Case Report and Review of the Literature

Cappellari

Rossetti

Avignone

et al. 2020

Journal of Pediatric Neurology

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Metronidazole-induced encephalopathy is a rare toxic encephalopathy secondary to the common use to this antimicrobial drug. It has been reported mainly in adult patients but only rarely in children. Owing to possible devastating complication of this disease, clinicians should have a higher index of suspicion for encephalopathic patients on metronidazole therapy. Here, we report a 5-month-old infant with metronidazole-induced encephalopathy presenting with nonconvulsive status epilepticus. A review of the literature in pediatric, as well as adult metronidazole-induced encephalopathy, is also provided.

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Metronidazole-induced encephalopathy: a systematic review

Cited by 94 publications

References 121 publications

NTR 2.0: a rationally-engineered prodrug converting enzyme with substantially enhanced efficacy for targeted cell ablation

NTR 2.0: a rationally-engineered prodrug converting enzyme with substantially enhanced efficacy for targeted cell ablation

Travel-associated neurological disease terminated in a postmortem diagnosed atypical HSV-1 encephalitis after high-dose steroid therapy – a case report

Pediatric Metronidazole-Induced Encephalopathy: A Case Report and Review of the Literature

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