Bedside Clinical Question:
Why do we dose Metronidazole every 12 hours instead of every 8 hours in most infections?
Background:
Metronidazole has been successfully used in practice for several decades and is still considered the drug of choice for treating many anaerobic infections.
Commonly, metronidazole is dosed every 8 hours.
However, pharmacokinetic data shows that the half-life of metronidazole is 8–12hr, and blood levels at 12hr exceed the MIC for most anaerobic infections.
Answer:
A study by Soule et al. compared every 8hr and every 12hr dosing of metronidazole to evaluate the frequency of clinical cure rates among their patients. They found no significant differences between the two regimens.
In terms of their defined secondary endpoints, which included duration of antibiotic therapy, hospital LOS, escalation of antibiotic treatment, microbiologic cure, and mortality, no significant differences were noted between the two groups.
Conclusion:
The Soule et al. study supports existing pharmacokinetic data where Metronidazole can be administered as an every 12hr regimen for most infections because of its long half-life (8-10 hours) resulting in trough levels above the MIC's for virtually all susceptible anaerobes.
Exceptions to every 12hr regimen, which should be every 8hr are in severe infections like Necrotizing Fasciitis, Fournier's, CNS infections, and severe C. Diff.
Written and reviewed by: Joanne C Routsolias, PharmD, RN, BCPS
Clinical PharmD Specialist - Emergency Medicine/Toxicology
Reference:
Soule AF, Green SB, Blanchette LM. Clinical efficacy of 12-h metronidazole dosing regimens in patients with anaerobic or mixed anaerobic infections. Ther Adv Infect Dis. 2018 May;5(3):57-62. PMID: 29796265