Efficacy and safety of high-dose tigecycline for the treatment of infectious diseases

Abstract Background: High-dose (HD) tigecycline regimen is increasingly used in infectious diseases, however its efficacy and safety versus low-dose (LD) is still unclear. Methods: A systematic review and meta-analysis was performed; PubMed, Embase, Cochrane Library, ScienceDirect, Web of Science, clinicalTrials.gov, Wanfang, VIP, and China National Knowledge Infrastructure (CNKI), were searched using terms “tigecycline” AND “dose” up to October 31, 2018. Eligible studies were randomized trials or cohort studies comparing mortality, clinical response, microbiological eradication and safety of different tigecycline dose regimens for any bacterial infection. The primary outcome was mortality, and the secondary outcomes were clinical response rate, microbiological eradiation rate and adverse events (AEs). Meta-analysis was done with random-effects model, with risk ratios (RR) and 95% confidence intervals (CI) calculated for all outcomes. Results: Of 951 publications retrieved, 17 studies (n = 1041) were pooled in our meta-analysis. The primary outcome was available in 11 studies, and the RR for mortality was 0.67 (95% CI 0 .53–0.84, P < .001). Clinical response ( RR 1.46, 95% CI 1.30–1.65, P < .001) and microbiological eradication rate ( RR 1.61, 95% CI 1.35–1.93, P < .001) were both higher in HD than in LD tigecycline regimen. However, non-Chinese study subgroup presented no statistical significance between HD and LD regimen, RR for mortality, clinical response and microbiological eradication were 0.79 (95% CI 0 .56–1.14, P = .21), 1.35 (95% CI 0 .96–1.92, P = .26), 1.00 (95% CI 0 .22–4.43, P = 1.00), respectively. AEs did not differ between HD and LD tigecycline ( RR 1.00, 95% CI 0 .80–1.26, P = .97). Conclusion: HD tigecycline regimen reduced mortality meanwhile improved clinical efficacy and should be considered in serious infections caused by multidrug-resistant and extensively drug-resistant (MDR/XDR) bacteria.