Antibiotics | Evaluating Clinical Outcomes of Intravenous Metronidazole Administration Every 12 Hours Versus Every 8 Hours for Intra-Abdominal Infections

This study compared the clinical efficacy of two metronidazole dosing intervals in treating intra-abdominal infections, demonstrating no significant difference in clinical cure rates between the 12-hour and 8-hour schedules. It provides clinical evidence for optimizing metronidazole administration protocols. The study data originates from multi-center retrospective analysis, offering practical reference value.

 

Literature Overview
The article 'Assessing Clinical Outcomes of Metronidazole for Intra-Abdominal Infections When Dosed Every 12 h Versus Every 8 h in a Multi-Center Health System', published in the journal Antibiotics, reviews and summarizes clinical applications of metronidazole in patients with intra-abdominal infections, evaluating therapeutic efficacy between 8-hour and 12-hour dosing intervals. Through multi-center retrospective cohort analysis, the study investigates the impact of different dosing regimens on clinical cure rates, antibiotic escalation, length of hospitalization, and 30-day readmission rates. The research enrolled 201 patients, with 103 receiving 8-hour intervals and 98 receiving 12-hour intervals. Analysis revealed comparable clinical effectiveness between dosing schedules, offering new insights for rational antibiotic use.

Background Knowledge
Intra-abdominal infections (IAI) are common infectious diseases typically caused by bacterial infections in abdominal organs (e.g., appendix, gallbladder, colon), often involving mixed infections with Gram-negative and Gram-positive bacteria. Metronidazole is a widely used antibiotic particularly effective against anaerobic bacterial infections due to its high sensitivity to anaerobic microorganisms. According to the 2017 Surgical Infection Society guidelines, metronidazole is recommended as a first-line empirical treatment for IAI due to its excellent tissue penetration, strong tolerability, and low adverse reaction incidence. However, metronidazole's pharmacokinetic profile supports extended 12-hour dosing intervals. With intravenous formulation shortages, healthcare institutions have been forced to adjust administration frequencies. Therefore, investigating the clinical impact of different dosing intervals holds practical significance for optimizing antibiotic strategies, improving patient compliance, and reducing adverse reaction risks.

 

 

Research Methods and Experiments
This multi-center retrospective cohort study enrolled 201 adult patients diagnosed with intra-abdominal infections, treated between January-July 2021 (8-hour dosing group) and January-November 2023 (12-hour dosing group). Inclusion criteria required radiologically confirmed intra-abdominal infections plus white blood cell count >12,000 cells/µL or body temperature >100.4°F. Primary endpoint was clinical cure, defined as resolution of infection symptoms with normalization of white blood cell count or temperature. Secondary endpoints included clinical failure, duration of treatment, length of hospitalization, and 30-day readmission rates.

Key Conclusions and Perspectives

• No significant difference in clinical cure rates between 12-hour and 8-hour dosing groups (63.2% vs. 69.9%, p=0.318)
• Comparable treatment durations between groups (median 4 days, p=0.509)
• Higher clinical failure rate in 12-hour group (21.4% vs. 8.7%, p=0.01), primarily attributed to requiring broader Gram-negative coverage rather than anaerobic coverage
• 12-hour group showed slightly longer hospital stays (4.9 days vs. 4.2 days, p=0.026) but no significant difference in 30-day readmission rates (14.2% vs. 8.7%, p=0.217)
• Findings demonstrate metronidazole's 12-hour dosing achieves equivalent clinical cure rates to 8-hour schedules while potentially reducing adverse reactions and improving patient compliance

Research Significance and Prospects
This study represents the first multi-center evaluation of 8-hour versus 12-hour metronidazole dosing for intra-abdominal infections, providing clinical evidence for adjusting administration frequencies. Prospective studies are still needed to validate these findings for broader clinical application. Additionally, metronidazole's pharmacokinetic profile supports extended dosing intervals with reduced daily doses, potentially offering more convenient treatment options in resource-limited or outpatient settings.

 

 

Conclusion
Through retrospective multi-center analysis, this study found no significant difference in clinical cure rates between 12-hour and 8-hour metronidazole dosing regimens for intra-abdominal infections. Although the 12-hour group showed higher clinical failure rates, this primarily resulted from requiring broader Gram-negative coverage rather than worsening anaerobic infections. The 12-hour regimen demonstrated comparable treatment duration and 30-day readmission rates, suggesting feasibility for specific patient populations. Findings support the rationale for extended dosing intervals during intravenous formulation shortages or clinical needs. Prospective studies should further validate efficacy and safety across diverse populations to establish broader evidence for clinical practice.

 

Sarah Galante, Ramya Castillo, Todd Price, MaiCuc Tran, and Stefanie Stramel-Stafford. Assessing Clinical Outcomes of Metronidazole for Intra-Abdominal Infections When Dosed Every 12 h Versus Every 8 h in a Multi-Center Health System. Antibiotics.