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The Safety and Efficacy of Ceftazidime-Avibactam Plus Metronidazole Versus Meropenem for Intra-abdominal Infections:
Mahmoud Ismail Nouh1, Hala AlButi2, Hani Raka Karrar3
1Research and Continuing Education Committee, Pharmaceutical Care Department, King Fahad Armed Forces Hospital, Jeddah, SAU.
Abstract:
Intra-abdominal infections encompass a range of medical conditions categorized by their complexity. Uncomplicated infections involve inflammation or infection limited to a single abdominal organ, such as acute appendicitis or cholecystitis, without extending to the peritoneum, while complicated infections spread to the peritoneal cavity. The key associated microbiological agents include Gram-positive cocci, Gram-negative Enterobacteriaceae, and obligate anaerobes, with common pathogens being Escherichia coli, Klebsiella pneumoniae, Streptococcus species, and Bacteroides fragilis. Treatment options include well-established antibiotics and newer agents like meropenem, metronidazole, and ceftazidime/avibactam. Meropenem, a carbapenem antibiotic, is known for its broad-spectrum efficacy and low toxicity, making it suitable for severe infections. Ceftazidime, a third-generation cephalosporin, is effective against Pseudomonas aeruginosa, especially when paired with avibactam, a β-lactamase inhibitor, enhancing its effectiveness. Metronidazole disrupts bacterial DNA, targeting anaerobic bacteria and protozoa. This systematic review and meta-analysis aimed to evaluate the safety and efficacy of the ceftazidime-avibactam plus metronidazole combination compared to meropenem for intra-abdominal infections. Following the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines, a comprehensive search of databases such as PubMed, Web of Science, and the Cochrane Library was conducted. Results showed that the combination therapy had a slightly higher overall adverse event rate (5.57%) compared to meropenem (4.56%), although this difference was not statistically significant [risk ratio (RR): 1.22; 95% confidence interval (CI): 0.78-1.93; p = 0.39]. Meropenem demonstrated a significantly higher clinical response rate in ceftazidime-susceptible infections (89.93% vs. 85.88%; RR: 0.96; 95% CI: 0.93-0.99; p = 0.009). No significant differences were observed in ceftazidime-resistant infections. Overall, the findings suggest that ceftazidime-avibactam combined with metronidazole is a viable alternative to meropenem, highlighting the need for further research to optimize treatment strategies amid rising antibiotic resistance.
Insights
This study compared ceftazidime-avibactam plus metronidazole to meropenem for intra-abdominal infections. Meropenem showed a higher clinical response rate in susceptible infections, but both treatments were viable alternatives amid rising antibiotic resistance.
Area of Science:
- Infectious Diseases
- Microbiology
- Pharmacology
Background:
- Intra-abdominal infections (IAIs) range from uncomplicated to complicated, involving various pathogens like Escherichia coli and Bacteroides fragilis.
- Current treatments include meropenem, metronidazole, and ceftazidime/avibactam, with concerns about rising antibiotic resistance.
- Meropenem offers broad-spectrum efficacy, while ceftazidime/avibactam targets resistant Gram-negative bacteria, and metronidazole covers anaerobes.
Purpose of the Study:
- To systematically review and meta-analyze the safety and efficacy of ceftazidime-avibactam plus metronidazole versus meropenem for IAIs.
- To compare clinical response rates and adverse event profiles between the two treatment regimens.
Main Methods:
- A systematic review and meta-analysis adhering to Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines.
- Comprehensive literature search across PubMed, Web of Science, and the Cochrane Library.
- Comparative analysis of safety (adverse events) and efficacy (clinical response rates).
Main Results:
- The ceftazidime-avibactam plus metronidazole combination showed a slightly higher, though not statistically significant, overall adverse event rate (5.57%) compared to meropenem (4.56%).
- Meropenem demonstrated a significantly higher clinical response rate in ceftazidime-susceptible infections (89.93% vs. 85.88%).
- No significant differences in outcomes were observed for ceftazidime-resistant infections.
Conclusions:
- Ceftazidime-avibactam plus metronidazole is a viable alternative treatment for intra-abdominal infections.
- Meropenem remains a strong option, particularly for ceftazidime-susceptible infections.
- Further research is crucial to optimize treatment strategies in the context of increasing antibiotic resistance.
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