Novel β-lactam/β-lactamase inhibitor combinations versus alternative antibiotics in adults with hospital-acquired pneumonia or ventilator-associated pneumonia: an integrated analysis of three randomised controlled trials.

OBJECTIVES

This study assessed the efficacy and safety of novel β-lactam/β-lactamase inhibitor (BL/BLI) combinations in adult patients with hospital-acquired pneumonia (HAP) or ventilator-associated pneumonia (VAP).

METHODS

PubMed, Web of Science, the Cochrane Library, Ovid MEDLINE, Embase and EBSCO databases were searched for randomised controlled trials (RCTs) published before 13 September 2020. Only RCTs comparing the treatment efficacy of novel BL/BLI combinations with other antibiotics for HAP/VAP in adult patients were included in this integrated analysis.

RESULTS

Three RCTs were included and no significant difference in clinical cure rate of test of cure was observed between the novel BL/BLI combinations and comparators [odds ratio (OR) = 1.01, 95% confidence interval (CI) 0.81-1.27; I = 35%]. The 28-day all-cause mortality was 16.2% and 17.6% for patients receiving novel BL/BLI combinations and comparators, respectively, and no significant difference was noted (OR = 0.90, 95% CI 0.69-1.16; I = 11%). Compared with comparators, novel BL/BLI combinations were associated with a similar microbiological response (OR = 1.06, 95% CI 0.73-1.54; I = 64%) and a similar risk of adverse events (AEs) [treatment-emergent AEs (TEAEs): OR = 1.04, 95% CI 0.83-1.30; I = 0%; serious AEs: OR = 1.14, 95% CI 0.79-1.63; I = 68%; treatment discontinuation for TEAE: OR = 0.90, 95% CI 0.62-1.31; I = 11%).

CONCLUSION

Clinical and microbiological responses of novel BL/BLI combinations in the treatment of HAP/VAP were similar to those of other available antibiotics. These combinations also shared a similar safety profile to comparators.