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负荷剂量黏菌素与碳青霉烯类药物治疗产超广谱β-内酰胺酶肠杆菌科的疗效比较。

Efficacy of loading dose colistin versus carbapenems for treatment of extended spectrum beta lactamase producing Enterobacteriaceae.

机构信息

Department of Pharmaceutical Care, Faculty of Pharmacy, Chiang Mai University, Chiang Mai, 50200, Thailand.

Epidemiology Research Group of Infectious Disease (ERGID), Chiang Mai University, Chiang Mai, 50200, Thailand.

出版信息

Sci Rep. 2021 Jan 8;11(1):18. doi: 10.1038/s41598-020-78098-4.

Abstract

Colistin provides in vitro activity against numerous ESBL-producing and carbapenem-resistant bacteria. However, clinical information with respect to its utilization in infection caused by ESBL producers is limited. The aim of this study was a comparison of mortality rates of loading dose (LD) colistin and carbapenems as definitive therapies in a cohort of patients with infections caused by ESBL-producing Escherichia coli and Klebsiella pneumoniae. A retrospective cohort study in 396 patients with ESBL-producing E.coli and K.pneumoniae infection at a university-affiliated hospital was conducted between 1 January 2005 and 30 June 2015 to compare outcomes of infected patients who received LD colistin (95 patients) with carbapenems (301 patients). The three primary outcomes were 30-day mortality, clinical response and microbiological response. The most common infection types were urinary tract infection (49.49%), followed by pneumonia (40.66%), bacteremia (13.64%), skin and soft tissue infections (4.80%) and intra-abdominal infection (3.03%). LD colistin group provided higher 30-day mortality when compared with carbapenems group (HR 7.97; 95% CI 3.68 to 17.25; P = 0.001). LD colistin was also independently associated with clinical failure (HR 4.30; 95% CI 1.93 to 9.57; P = 0.001) and bacteriological failure (HR 9.49; 95% CI 3.76 to 23.96; P = 0.001) when compared with those who received carbapenems. LD colistin treatment was associated with poorer outcomes, i.e. mortality rate, clinical response and microbiological response. Moreover, when adjusted confounding factors, LD colistin was still less effective than carbapenems. It should be noted that, however, the use of Vitek-2 to assess colistin susceptibility could provide inaccurate results. Also, the difference in baseline characteristics could still remain in retrospective study although compensation by hazard ratio adjustment was performed. Therefore, clinical utilization of LD colistin should be recommended as an alternative for treatment ESBL-producing Enterobacteriaceae only in the circumstances where carbapenems cannot be utilized, but this recommendation must be considered carefully.

摘要

黏菌素对许多产 ESBL 和碳青霉烯类耐药的细菌具有体外活性。然而,关于其在产 ESBL 细菌感染中的应用的临床信息是有限的。本研究的目的是比较负荷剂量(LD)黏菌素和碳青霉烯类药物作为产 ESBL 大肠埃希菌和肺炎克雷伯菌感染患者确定性治疗的死亡率。

在 2005 年 1 月 1 日至 2015 年 6 月 30 日期间,对一家大学附属医院的 396 名产 ESBL 大肠埃希菌和肺炎克雷伯菌感染患者进行了一项回顾性队列研究,比较了接受 LD 黏菌素(95 例)和碳青霉烯类药物(301 例)治疗的感染患者的结局。三个主要结局是 30 天死亡率、临床反应和微生物学反应。最常见的感染类型是尿路感染(49.49%),其次是肺炎(40.66%)、菌血症(13.64%)、皮肤软组织感染(4.80%)和腹腔内感染(3.03%)。

与碳青霉烯类药物相比,LD 黏菌素组的 30 天死亡率更高(HR 7.97;95%CI 3.68 至 17.25;P=0.001)。与接受碳青霉烯类药物的患者相比,LD 黏菌素也与临床失败(HR 4.30;95%CI 1.93 至 9.57;P=0.001)和细菌学失败(HR 9.49;95%CI 3.76 至 23.96;P=0.001)独立相关。

LD 黏菌素治疗与较差的结局相关,即死亡率、临床反应和微生物学反应。此外,即使通过风险比调整进行了补偿,在调整混杂因素后,LD 黏菌素的疗效仍然不如碳青霉烯类药物。

需要注意的是,然而,使用 Vitek-2 评估黏菌素敏感性可能会导致不准确的结果。此外,尽管通过风险比调整进行了补偿,但在回顾性研究中,基线特征的差异仍然存在。因此,只有在不能使用碳青霉烯类药物的情况下,才应推荐 LD 黏菌素作为治疗产 ESBL 肠杆菌科细菌的替代药物,但必须慎重考虑这一建议。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2336/7794528/54c81e542fa6/41598_2020_78098_Fig1_HTML.jpg

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