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Assessing Clinical Outcomes of Metronidazole for Intra-Abdominal Infections When Dosed Every 12 h Versus Every 8 h in
Sarah Galante1, Ramya Castillo1, Todd Price1
1Memorial Hermann Memorial City Medical Center, Houston, TX 77024, USA.
Abstract:
Background: Metronidazole is the preferred anaerobic agent for empiric treatment of intra-abdominal infections (IAI). Although dosed every 8 h (q8hr), blood concentrations exceed the in vitro minimum inhibitory concentration (MIC) for anaerobic organisms at 12 h (q12hr). A drug shortage of intravenous (IV) metronidazole prompted the conversion to every 12 h dosing in qualifying patients treated for IAI. Objective: To determine efficacy outcomes of metronidazole dosed every 12 h versus every 8 h in patients treated for IAI. Methods: This was a multi-center, retrospective, cohort study of 201 patients from January to July 2021 (q8hr) and January to November 2023 (q12hr) at five hospitals through the greater Houston area. Included patients were adults with a diagnosis of IAI confirmed by radiographic evidence and a white blood count (WBC) > 12,000 cells/µL and/or temperature > 100.4 °F at the time of diagnosis. The primary outcome was clinical cure of IAI, defined as resolution of signs/symptoms of IAI and normalization of WBC or temperature. Results: A total of 201 patients were included, 103 patients in the q8hr group and 98 patients in the q12hr group. Clinical cure of IAI occurred in 72 patients (69.9%) in the q8hr group and 62 patients (63.2%) in the q12hr group (p = 0.318). The median duration of therapy days was similar for both groups (4.0 [4.0-6.0] vs. 4.0 [3.0-6.0] (p = 0.509)). The frequency of clinical failure was higher in the q12hr group (8.7% vs. 21.4%; p = 0.01). Seven patients in the q8hr group and fourteen patients in the q12hr group required escalation of antibiotics due to the need for broader-spectrum antimicrobial therapy by clinical failure definition. Conclusions: There was no difference in clinical cure of IAI with an extended dosing interval. Clinical failure and escalation in antibiotics was higher in the q12h group due to the need for broader-spectrum gram-negative coverage and not related to the need for anaerobic coverage. Findings suggest that every 12 h dosing has similar outcomes.
Insights
Extended metronidazole dosing every 12 hours showed similar clinical cure rates for intra-abdominal infections (IAI) compared to every 8 hours. However, the 12-hour interval was associated with increased clinical failure and antibiotic escalation.
Area of Science:
- Infectious Diseases
- Pharmacology
- Clinical Pharmacy
Background:
- Metronidazole is a key anaerobic agent for intra-abdominal infections (IAI).
- Standard dosing is every 8 hours (q8hr), but concentrations remain effective for 12 hours (q12hr).
- Intravenous metronidazole shortages led to a shift towards q12hr dosing for IAI.
Purpose of the Study:
- To compare the efficacy of metronidazole dosed every 12 hours versus every 8 hours in IAI patients.
- To evaluate clinical cure rates and treatment outcomes between the two dosing regimens.
Main Methods:
- Multi-center, retrospective cohort study of 201 adult patients with radiographically confirmed IAI.
- Patients received either q8hr or q12hr intravenous metronidazole dosing.
- Primary outcome: clinical cure, defined by resolution of IAI signs/symptoms and normalization of WBC or temperature.
Main Results:
- Clinical cure rates were similar: 69.9% for q8hr versus 63.2% for q12hr (p=0.318).
- Clinical failure was significantly higher in the q12hr group (21.4%) compared to the q8hr group (8.7%) (p=0.01).
- Antibiotic escalation was more frequent in the q12hr group, driven by the need for broader gram-negative coverage.
Conclusions:
- Extended metronidazole dosing every 12 hours did not significantly impact clinical cure rates for IAI.
- The q12hr regimen was associated with increased clinical failure and antibiotic escalation, primarily due to inadequate gram-negative coverage, not anaerobic coverage.
- Current findings suggest comparable outcomes for q12hr dosing, but careful patient selection and monitoring for broader coverage needs are essential.
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