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大剂量替加环素治疗感染性疾病的疗效与安全性:一项荟萃分析。

Efficacy and safety of high-dose tigecycline for the treatment of infectious diseases: A meta-analysis.

作者信息

Gong Jinhong, Su Dan, Shang Jingjing, Yu Hai, Du Guantao, Lin Ying, Sun Zhiqiang, Liu Guangjun

机构信息

Department of Pharmacy, The Affiliated Changzhou No. 2 People's Hospital of Nanjing Medical University, Changzhou.

Department of Pharmaceutics, College of Pharmaceutical Sciences, Soochow University, Suzhou.

出版信息

Medicine (Baltimore). 2019 Sep;98(38):e17091. doi: 10.1097/MD.0000000000017091.

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.

摘要

背景

高剂量替加环素方案在传染病治疗中的应用日益广泛,但其与低剂量方案相比的疗效和安全性仍不明确。

方法

进行了一项系统评价和荟萃分析;检索了截至2018年10月31日的PubMed、Embase、Cochrane图书馆、ScienceDirect、Web of Science、clinicalTrials.gov、万方、维普和中国知网,使用“替加环素”和“剂量”等检索词。符合条件的研究为比较不同替加环素剂量方案治疗任何细菌感染的死亡率、临床反应、微生物清除率和安全性的随机试验或队列研究。主要结局为死亡率,次要结局为临床反应率、微生物清除率和不良事件(AE)。采用随机效应模型进行荟萃分析,计算所有结局的风险比(RR)和95%置信区间(CI)。

结果

在检索到的951篇文献中,17项研究(n = 1041)纳入了我们的荟萃分析。11项研究提供了主要结局,死亡率的RR为0.67(95%CI 0.53 - 0.84,P <.001)。高剂量替加环素方案的临床反应(RR 1.46,95%CI 1.30 - 1.65,P <.001)和微生物清除率(RR 1.61,95%CI 1.35 - 1.93,P <.001)均高于低剂量方案。然而,非中国研究亚组中高剂量和低剂量方案之间无统计学差异,死亡率、临床反应和微生物清除率的RR分别为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)。高剂量和低剂量替加环素的不良事件无差异(RR 1.00,95%CI 0.80 - 1.26,P =.97)。

结论

高剂量替加环素方案可降低死亡率,同时提高临床疗效,对于多重耐药和广泛耐药(MDR/XDR)细菌引起的严重感染应予以考虑。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b8ee/6756684/fd6a296f29cc/medi-98-e17091-g001.jpg

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