A comparison of clinical outcomes associated with dosing metronidazole every 8 hours versus every 12 hours: a systematic review and metaanalysis.

Background:Metronidazole treats obligate anaerobic bacterial and protozoal infections, with an elimination half-life of around 8 hours. The long elimination half-life, the favorable ratio of steady-state serum levels to minimum inhibitory concentration, and the presence of active metabolites have led to the consideration of metronidazole use at 12-hour dosage intervals. This systematic review aimed to compare the clinical outcomes of twice-daily and thrice-daily metronidazole dosing. Methods:Using the PRISMA checklist, we searched five databases to systematically identify all relevant studies published up to June 16, 2023. Results:The final analysis included two published retrospective cohort studies of hospitalized adult patients: a single site study (n = 200) and a multisite study (n = 85) of "good" quality, as measured by the Newcastle-Ottawa scale. The reported baseline characteristics of the 8-hour and 12-hour dosing groups were comparable, and neither study identified significant differences in primary and secondary clinical outcomes. Metaanalysis of the need to escalate antibiotic therapy also showed no statistically significant differences using the Mantel-Haenszel fixed-effect method (95% confidence interval: 47.6% lower to 6.4 times higher risk, P = 0.34) and inverse-variance method (risk ratio: 1.87; 95% confidence interval: 0.52-6.65, P = 0.34). Conclusions:This review suggests that dosing metronidazole every 12 hours is as effective as every-8-hour dosing for hospitalized patients with anaerobic infections. These encouraging findings would benefit from validation by a multicenter randomized controlled trial since there would be many benefits to a 12-hour dosing interval while achieving similar clinical outcomes with traditional dosing. The studies in this systematic review excluded patients with Clostridioides difficile and central nervous system and amebiasis infections, so the findings do not apply to these infection types.