Systematic review and meta-analysis of the effectiveness and safety of tigecycline for treatment of infectious disease

Abstract

The aim of this study was to compare the efficacy and safety of tigecycline, a newly developed glycylcycline antibiotic, with those of empirical antibiotic regimens which have been reported to possess good efficacy for complicated skin and skin structure infections (cSSSIs), complicated intra-abdominal infections (cIAIs), community-acquired pneumonia (CAP), and other infections caused by methicillin-resistant Staphylococcus aureus (MRSA) or vancomycin-resistant Enterococcus (VRE). A meta-analysis of randomized controlled trials (RCTs) identified in PubMed, the Cochrane Library, and Embase was performed. Eight RCTs involving 4,651 patients were included in the meta-analysis. Compared with therapy with empirical antibiotic regimens, tigecycline monotherapy was associated with similar clinical treatment success rates (for the clinically evaluable [CE] population, odds ratio [OR] = 0.92, 95% confidence interval [CI] = 0.76 to 1.12, P = 0.42; for the clinical modified intent-to-treat [c-mITT] population, OR = 0.86, 95% CI = 0.74 to 1.01, P = 0.06) and similar microbiological treatment success rates (for the microbiologically evaluable [ME] population, OR = 0.86, 95% CI = 0.69 to 1.07, P = 0.19). The incidence of adverse events in the tigecycline group was significantly higher than that in the other therapy groups with a statistical margin (for the modified intent-to-treat [mITT] population, OR = 1.33, 95% CI = 1.17 to 1.52, P < 0.0001), especially in the digestive system (mITT population, OR = 2.41, 95% CI = 1.67 to 3.46, P < 0.00001). No difference regarding all-cause mortality and drug-related mortality between tigecycline and the other regimens was found, although numerically higher mortality was found in the tigecycline group. This meta-analysis provides evidence that tigecycline monotherapy may be used as effectively as the comparison therapy for cSSSI, cIAIs, CAP, and infections caused by MRSA/VRE. However, because of the high risk of mortality, AEs, and emergence of resistant isolates, prudence with the clinical use of tigecycline monotherapy in infections is required.

FIG. 1.

Flow diagram of the RCTs reviewed.

FIG. 2.

Meta-analysis of treatment success based on CE and c-mITT populations. df, degrees of freedom; M-H, Mantel-Haenszel method.

FIG. 3.

Meta-analyses of pathogen eradication in total and for MSSA, MRSA, Streptococcus pneumoniae, Escherichia coli, and Enterococcus faecalis (non-VRE) for ME population. df, degrees of freedom; M-H, Mantel-Haenszel method.

FIG. 4.

Meta-analyses of adverse effects probably or possibly related to studied medications. df, degrees of freedom; M-H, Mantel-Haenszel method.

FIG. 4.

Meta-analyses of adverse effects probably or possibly related to studied medications. df, degrees of freedom; M-H, Mantel-Haenszel method.

FIG. 5.

Meta-analyses of all-cause mortality and mortality possibly related to study drug. df, degrees of freedom; M-H, Mantel-Haenszel method.