Novel β-Lactam/β-Lactamase inhibitor combinations vs alternative antibiotics in the treatment of complicated urinary tract infections: A meta-analysis of randomized controlled trials

OBJECTIVES: This meta-analysis assessed the efficacy and safety of novel β-lactam/β-lactamase inhibitor combinations in the treatment of complicated urinary tract infection (cUTI)/acute pyelonephritis (APN). METHODS: PubMed, Web of Science, EBSCO (Elton B. Stephens Co.), Cochrane Library, Ovid MEDLINE, and Embase databases were accessed until November 21, 2019. In this meta-analysis, only randomized controlled trials comparing the treatment efficacy of novel β-lactam/β-lactamase inhibitor combinations with other antibiotics for cUTI/APN in adult patients were included. The outcomes included the clinical and microbiological responses, and risk of adverse events (AEs). RESULTS: Overall, the experimental group treated with a novel β-lactam/β-lactamase inhibitor combination and the control group comprised 1346 and 1376 patients, respectively. No significant difference in the clinical response rate at test-of-cure was observed between the novel β-lactam/β-lactamase inhibitor combination and comparators among the microbiological modified intent-to-treat population (89.1% vs 88.3%, OR, 1.04; 95% confidence interval [CI], 0.76–1.42; I(2) = 28%) and the microbiologically evaluable population (95.2% vs 94.7%, OR, 1.12; 95% CI, 0.68–1.84; I(2) = 0%). Additionally, the novel β-lactam/β-lactamase inhibitor combination was associated with a better microbiological response at test-of-cure than the comparators among the microbiological modified intent-to-treat population (74.4% vs 68.5%, OR, 1.34; 95% CI, 1.04–1.72; I(2) = 45%) and microbiologically evaluable population (80.1% vs 72.5%, OR, 1.49; 95% CI, 1.06–2.10; I(2) = 58%). Finally, the risk of AEs associated with the novel β-lactam/β-lactamase inhibitor combination was similar to that associated with the comparators (treatment-emergent adverse events [TEAE], OR, 1.04; 95% CI, 0.87–1.23; I(2) = 19%; serious AEs, OR, 1.21; 95% CI, 0.82–1.76; I(2) = 0%; treatment discontinuation for drug-related TEAE, OR, 077; 95% CI, 0.38–1.56, I(2) = 5%). The all-cause mortality did not differ between the novel β-lactam/β-lactamase inhibitor combination and comparators (OR, 1.19; 95% CI, 0.37–3.81; I(2) = 0%). CONCLUSIONS: The clinical and microbiological responses of novel β-lactam/β-lactamase inhibitor combinations in the treatment of cUTI/APN are similar to those of other available antibiotics. These combinations also share a safety profile similar to that of other antibiotics.