替加環(huán)素治療耐碳青霉烯類(lèi)肺炎克雷伯菌效果的Meta分析

侯思遠(yuǎn) 譚永峰 馮星火

[摘要]目的 系統(tǒng)評(píng)價(jià)替加環(huán)素單藥治療以及聯(lián)合治療耐碳青霉烯類(lèi)肺炎克雷伯菌的效果。方法 通過(guò)計(jì)算機(jī)檢索自建庫(kù)到2018年9月Cochrane圖書(shū)館、EmBase、PubMed、中國(guó)期刊全文數(shù)據(jù)庫(kù)（CNKI）以及中國(guó)生物醫(yī)學(xué)文獻(xiàn)數(shù)據(jù)庫(kù)（CBM）關(guān)于替加環(huán)素治療耐碳青霉烯類(lèi)肺炎克雷伯菌的臨床研究。由2名研究者按入選與排除標(biāo)準(zhǔn)獨(dú)立篩選試驗(yàn)，并對(duì)納入研究的方法學(xué)質(zhì)量進(jìn)行評(píng)價(jià)，提取資料，采用Review Manager 5.3軟件對(duì)數(shù)據(jù)進(jìn)行Meta分析，計(jì)算比值比（OR）和95%置信區(qū)間（95%CI）。結(jié)果 最終本研究納入了9篇臨床試驗(yàn)。替加環(huán)素單藥治療與其他單藥治療對(duì)耐碳青霉烯類(lèi)肺炎克雷伯菌感染患者的死亡率比較，差異無(wú)統(tǒng)計(jì)學(xué)意義（OR=1.07，95%CI=0.63～1.82，P=0.8）。以替加環(huán)素為基礎(chǔ)的聯(lián)合治療與其他藥物聯(lián)合治療相比，對(duì)耐碳青霉烯類(lèi)肺炎克雷伯菌感染患者的死亡率差異無(wú)統(tǒng)計(jì)學(xué)意義（OR=1.40，95%CI=0.89～2.21，P=0.15）。結(jié)論 無(wú)論是替加環(huán)素單藥還是以替加環(huán)素為基礎(chǔ)的聯(lián)合治療，均不能有效改善耐碳青霉烯類(lèi)肺炎克雷伯菌感染患者的死亡率。本結(jié)論尚需要更多大樣本、高質(zhì)量的臨床隨機(jī)對(duì)照試驗(yàn)予以證實(shí)。

[關(guān)鍵詞]替加環(huán)素;耐碳青霉烯類(lèi)肺炎克雷伯菌;單藥治療;聯(lián)合治療;Meta分析

[中圖分類(lèi)號(hào)] R453.2? ? ? ? ? [文獻(xiàn)標(biāo)識(shí)碼] A? ? ? ? ? [文章編號(hào)] 1674-4721（2019）2（c）-0064-04

[Abstrcat] Objective To systematically evaluate the efficacy of Tegacycline monotherapy and combination therapy in the treatment of carbapenem-resistant Klebsiella pneumonia （CRKP） infections. Methods The clinical studies of Tegacycline in the treatment of CRKP were retrieved from Cochrane Library， Embase， Pubmed， China National Knowledge Infrastructure （CNKI） and China Biology Medicine disc （CBM） by computer from the construction of the library to September 2018. Two reviewers independently retrieved studies according to the inclusion and exclusion criteria， assessed the methodological quality of included trials， and extracted data. The data analysis was performed by Review Manager 5.3 software. The odds ratio （OR） and 95% confidence intervals （CI） were calculated for outcome analysis. Results A total of 9 studies were included in this study. There was no significant difference in the mortality of CRKP infection between Tegacycline monotherapy and other monotherapy （OR=1.07， 95%CI=0.63-1.82， P=0.8）. There was no significant difference in mortality among CRKP patients treated with Tigacycline-based combination therapy compared with other drugs combination therapy （OR=1.40， 95%CI=0.89-2.21， P=0.15）. Conclusion Both Tigecycline monotherapy and Tigecycline-based combination therapy do not significantly improve the mortality of patients with CRKP infections. This conclusion needs more large sample and high quality clinical randomized controlled trials to confirm.

[Key words] Tigecycline; Carbapenem-resistant Klebsiella pneumoniae; Monotherapy; Combination therapy; Meta analysis

目前，耐碳青霉烯類(lèi)的肺炎克雷伯菌（carbapenem-resistant Klebsiella pneumoniae，CRKP）已經(jīng)成為世界范圍內(nèi)最重要的醫(yī)院感染病原體之一[1]，具有較高的死亡率、較長(zhǎng)的住院時(shí)間以及較高的住院花費(fèi)等特點(diǎn)[2-3]。CRKP對(duì)大多數(shù)可用抗菌藥物，包括碳青霉烯類(lèi)抗菌藥物，其產(chǎn)生耐藥性的能力迫使我們?nèi)で笮碌目垢腥局委煼桨浮?/p>

替加環(huán)素主要具有抑菌活性，分布較廣，但是在血清中濃度較低[18]。在使用替加環(huán)素治療CRKP感染的同時(shí)也可能導(dǎo)致替加環(huán)素耐藥的情況從而使治療失敗[19]。納入的研究中大多數(shù)患者為CRKB的血流感染患者，以上因素可能是導(dǎo)致在本研究中替加環(huán)素療效不滿(mǎn)意的主要原因。

當(dāng)然，本研究存在著很多的限制性。①影響死亡率的因素有很多，比如患者的年齡、基礎(chǔ)疾病狀態(tài)、是否擁有較高的APACHE Ⅱ評(píng)分等，這些都影響著患者的死亡率，而本研究?jī)H僅納入了全因死亡率這一個(gè)指標(biāo)去評(píng)價(jià)替加環(huán)素治療CRKP的效果，其中可能存在著較大的偏倚;②筆者無(wú)法從納入的研究中獲得更多大家關(guān)注的數(shù)據(jù)，比如臨床癥狀的改善、細(xì)菌清除率;③只有兩篇文獻(xiàn)交待了替加環(huán)素的用法用量，大多數(shù)的文獻(xiàn)均未交待具體的給藥方案，如果對(duì)不同劑量進(jìn)行亞組分析可能會(huì)減少偏倚的出現(xiàn);④納入的文獻(xiàn)都不是隨機(jī)對(duì)照研究，文獻(xiàn)的偏倚較高，可能會(huì)影響本研究的結(jié)果。

綜上所述，無(wú)論是替加環(huán)素單藥還是以替加環(huán)素為基礎(chǔ)的聯(lián)合治療，均并不能有效改善CRKP感染患者的死亡率，因此在治療上需要謹(jǐn)慎選擇。但是由于本研究納入文獻(xiàn)的偏倚風(fēng)險(xiǎn)較高，本結(jié)論尚需要更多大樣本、高質(zhì)量的臨床隨機(jī)對(duì)照試驗(yàn)予以證實(shí)。

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（收稿日期：2018-12-13 本文編輯：祁海文）