2025 Southeastern Residency Conference

Title: Optimizing Metronidazole Administration: A Comparative Analysis of Every Twelve Hours Versus Every Eight Hours Dosing for Anaerobic Infections 


Authors: Taylor J. Merritt, Kat Petersen, Benjamin Albrecht, Sujit Suchindran, Sarah B. Green 
Emory University Hospital- Atlanta, GA   


Background: Metronidazole has historically been the drug of choice for anaerobic infections, conventionally dosed every eight hours. Its hydroxy metabolite can exhibit 30-65% activity of the parent drug and has a half-life extending up to 11.65 hours. Serum levels of metronidazole exceed the minimum inhibitory concentration at twelve hours for most anaerobes. Thus, an argument that can be made for dosing every twelve hours for most anaerobic infections. The objective of this study is to determine the probability that patients receiving oral or intravenous metronidazole at a dosing frequency of every twelve hours would have a more or equivalent desirable outcome, measured by desirability of outcome ranking (DOOR), than patients receiving a traditional, every eight hours frequency for the treatment of confirmed anaerobic infections.   


Methods: This was a retrospective, quasi-experimental, multi-center analysis which reviewed adult patients who received metronidazole for the treatment of confirmed anaerobic infections. Included patients received 500 mg doses of intravenous or oral metronidazole at a dosing frequency of eight or twelve hours, for at least 72 hours in duration. Patients were excluded if the indication for metronidazole was hepatic encephalopathy, surgical prophylaxis, or treatment of Clostridioides difficile, central nervous system, parasitic, sexually transmitted, or Helicobacter pylori infections. Those who received metronidazole every eight hours for ≥ 72 hours before transition to every twelve hours, received concomitant antibiotics with anaerobic coverage for ≥ 72 hours, or had an organism with documented resistance to metronidazole were also excluded. The primary outcome was the probability that a patient receiving metronidazole every twelve hours would have a more or equivalent desirable outcome than a patient receiving every eight-hour dosing. Secondary outcomes included an assessment of outcomes specific to the subgroup of immunocompromised patients in the study. 


Results: Baseline demographics were similar between the two groups. The majority of included patients were male (55%), Black (62%), and had an average age of 61 years. The average length of stay was 22 days overall, which was also comparable amongst groups. The overall DOOR distribution between groups was similar and there was no significant difference in the probability of a more desirable outcome for patients who received metronidazole every twelve hours compared to traditional every eight-hour dosing (51.3% [95% CI: 43.5%, 59.0%]; p-value= 0.7417). Of the individual DOOR components, there was a statistically significant difference in treatment failure with a higher probability of desired result (i.e. treatment success) in the every twelve-hour dosing group (p-value= 0.021). Analysis of the immunocompromised subgroup also found no difference in probability of desirable outcomes (45.9% [95% CI: 30.1%, 62.6%]; p-value= 0.6388). 


Conclusion: We found no significant differences in desirable outcomes between the dosing groups for total study patients and the immunocompromised subgroup. The results discussed above included criteria for the DOOR analysis such as treatment failure, unsuccessful discharge, adverse effects, and transition to hospice or death. This provides evidence to support that every twelve hours dosing of metronidazole could be considered over every eight hours for most anaerobic infections, due to the similar DOOR ranking in addition to the time saving component, increased convenience for nursing staff, and expected reduction in cost in contrast to dosing every eight hours.