Polymyxin monotherapy versus polymyxin-based combination therapy against carbapenem-resistant Klebsiella pneumoniae: A systematic review and meta-analysis

• Polymyxins can be used to treat CR-KP BSI and VAP/HAP. • Polymyxin-based combination therapy provides survival benefit in treatment of CR-KP. • Polymyxin monotherapy is associated with higher mortality. • Inclusion of a carbapenem or tigecycline enhances the benefit of combination therapy. • Three-drug therapy including polymyxin shows significant survival benefit. This meta-analysis was performed to compare polymyxin monotherapy and polymyxin-based combination therapy for carbapenem-resistant Klebsiella pneumoniae (CR-KP) infections. We conducted searches on MEDLINE, Embase and Cochrane Collaborative database for both observational studies and randomised controlled trials (RCTs) comparing polymyxin monotherapy with polymyxin-based combination therapy in patients with CR-KP infection. The primary outcome was mortality. We divided all included studies into several groups according to different combination-combination and different infection types. The odds ratio (OR) and 95% confidence intervals (CI) were calculated for outcome analysis. Ten studies with 481 patients were included. Polymyxin monotherapy was associated with higher mortality than polymyxin-based combination therapy in treatment of CR-KP bloodstream infections (BSI) (OR 1.93, 95% CI 1.14–3.27, P = 0.01) and ventilator-associated pneumonia (VAP)/hospital-acquired pneumonia (HAP) (OR 3.82, 95% CI 1.15–12.71, P = 0.03). In subgroup analysis of different combinations, mortality was significantly higher with polymyxin monotherapy compared with combination therapy with tigecycline (OR 1.88, 95% CI 1.05–3.37, P = 0.03), or with cabapenem (OR 3.11, 95% CI 1.25–7.74, P = 0.01), but no differences were found in combinations with aminoglycosides (OR 1.29, 95% CI 0.72–2.29, P = 0.38). Three-drug combination therapy including polymyxin was also associated with significant survival benefit (OR 3.86, 95% CI 1.60–9.32, P = 0.003). Polymyxin-based combination therapy provides significant survival benefit in treatment of CR-KP, which appears to be more pronounced when a carbapenem or tigecycline is included in the regimen.