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Effect of adding metronidazole to meropenem on clinical efficacy in complicated intra-abdominal infections: a
Hajime Nakashima1, Motoyasu Miyazaki2, Naoaki Nishimura3
1Department of Pharmacy, Japan Community Health Care Organization Kyushu Hospital, 1-8-1, Kishinoura, Yahatanishi-ku, Kitakyushu-shi, Fukuoka, 806-0034, Japan. hajimenakashima0929@gmail.com.
Background:
Complicated intra-abdominal infections (cIAI), often caused by a diverse range of organisms, are commonly managed with appropriate empiric antimicrobial therapy, particularly broad-spectrum agents such as meropenem (MEPM). Anaerobes contribute to 30%-80% of the causative pathogens, and Bacteroides fragilis, a typical anaerobe, has been reported to exhibit increased resistance to antimicrobial agents. Metronidazole (MNZ) has shown significant antibacterial activity against anaerobes and a different mechanism of action; therefore, its addition to MEPM may improve its clinical efficacy. This study aimed to evaluate the impact of adding MNZ to MEPM on the clinical efficacy of empiric antimicrobial therapy for cIAI.
Methods:
This retrospective study spanned 9 years and included 114 patients who underwent empiric antimicrobial therapy with MEPM monotherapy or MEPM plus MNZ combination therapy for cIAI caused by lower gastrointestinal perforation in conjunction with surgery or percutaneous drainage. Propensity score matching was applied to adjust for background factors. The primary outcome was the cure rate, while secondary outcomes included 28-day mortality and the duration of hospitalization following surgical intervention.
Results:
There were no significant differences in the cure rates, 28-day mortality or hospitalization durations between the MEPM monotherapy group and the MEPM plus MNZ group [cure rates: 91.2% (83/91) vs. 91.3% (21/23), respectively, p = 0.999; 28-day mortality: 2.2% (2/91) vs. 4.3% (1/23), respectively, p = 0.495; hospitalization durations, median (interquartile range): 18 days (11.5-26.5) vs. 20 days (15.5-32.0), respectively; p = 0.214]. Twenty patients were selected for each group using propensity score matching. No significant differences were observed in cure rates, 28-day mortality, or hospitalization durations between the MEPM monotherapy group and the MEPM plus MNZ group [cure rates: 85.0% (17/20) vs. 95.0% (19/20), respectively, p = 0.605; 28-day mortality: 10% (2/20) vs. 5% (1/20), respectively, p = 0.999; hospitalization durations, median (interquartile range): 16 days (11.8-24) vs. 20.5 days (16.3-38.3), respectively; p = 0.184].
Conclusion:
In this single-center retrospective cohort, there was no evidence that adding MNZ to MEPM improved clinical efficacy in empiric antimicrobial therapy with infection-source control in cIAI.
Clinical Trial Number:
Not applicable.
Insights
Adding metronidazole (MNZ) to meropenem (MEPM) did not improve clinical outcomes for complicated intra-abdominal infections (cIAI). This study found no significant difference in cure rates or mortality when MNZ was combined with MEPM.
Area of Science:
- Infectious Diseases
- Clinical Pharmacology
- Surgical Infections
Background:
- Complicated intra-abdominal infections (cIAI) often involve polymicrobial infections, including anaerobes.
- Bacteroides fragilis shows increasing resistance to certain antimicrobial agents.
- Meropenem (MEPM) is a broad-spectrum antibiotic commonly used for cIAI, while metronidazole (MNZ) has activity against anaerobes.
Purpose of the Study:
- To evaluate the impact of adding metronidazole (MNZ) to meropenem (MEPM) on the clinical efficacy of empiric antimicrobial therapy for cIAI.
- To compare cure rates, 28-day mortality, and hospitalization duration between MEPM monotherapy and MEPM plus MNZ combination therapy.
Main Methods:
- A 9-year retrospective study of 114 patients with cIAI due to lower gastrointestinal perforation.
- Patients received either MEPM monotherapy or MEPM plus MNZ combination therapy.
- Propensity score matching was used to adjust for background factors and compare outcomes.
Main Results:
- No significant differences were observed in cure rates (91.2% vs. 91.3%) between the groups.
- 28-day mortality rates (2.2% vs. 4.3%) and hospitalization durations were also similar between the MEPM and MEPM plus MNZ groups.
- Post-propensity score matching analysis confirmed no significant differences in primary or secondary outcomes.
Conclusions:
- Adding metronidazole (MNZ) to meropenem (MEPM) did not demonstrate improved clinical efficacy for cIAI when infection-source control was achieved.
- The findings suggest that MEPM monotherapy may be sufficient for empiric treatment of cIAI in this patient population.
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