Colistin Versus Ceftazidime-Avibactam in the Treatment of Infections Due to Carbapenem-Resistant Enterobacteriaceae
Colistin Versus Ceftazidime-Avibactam in the Treatment of Infections Due to Carbapenem-Resistant Enterobacteriaceae
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DOI：
10.1093/cid/cix783
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发表时间：
2018-01-15
影响因子：
11.8
通讯作者：
Evans, Scott
中科院分区：
文献类型：
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作者：
van Duin, David;Lok, Judith J.;Evans, Scott
背景：头孢他啶 - 阿维巴坦（一种头孢菌素 - β - 内酰胺酶抑制剂组合，对产肺炎克雷伯菌碳青霉烯酶的碳青霉烯类耐药肠杆菌科细菌[CRE]具有体外活性）相较于黏菌素的疗效仍不明确。
方法：从肺炎克雷伯菌及其他肠杆菌科细菌碳青霉烯类耐药性研究联盟（CRACKLE，一项前瞻性、多中心、观察性研究）中选取最初因CRE感染接受头孢他啶 - 阿维巴坦或黏菌素治疗的患者。采用意向性治疗分析（含部分计分）以及结局排序合意性方法进行疗效、安全性和获益 - 风险分析。序贯疗效结果基于开始治疗后第30天的转归情况（出院回家、未出院但未观察到在医院死亡、在医院死亡）。所有分析均使用治疗权重的逆概率（IPTW）对混杂因素进行了调整。
结果：38例患者首先接受头孢他啶 - 阿维巴坦治疗，99例接受黏菌素治疗。大多数患者在治疗过程中还使用了其他抗CRE药物。血流感染（n = 63；46%）和呼吸道感染（n = 30；22%）最为常见。在接受头孢他啶 - 阿维巴坦治疗与接受黏菌素治疗的患者中，开始治疗30天后经IPTW调整的全因医院死亡率分别为9%和32%（差异为23%；95%自助法置信区间为9% - 35%；P = 0.001）。在对30天转归情况的分析中，与接受黏菌素治疗的患者相比，接受头孢他啶 - 阿维巴坦治疗的患者经IPTW调整后有更好结局的概率为64%（95%置信区间为57% - 71%）。部分计分分析表明头孢他啶 - 阿维巴坦在各方面均优于黏菌素。
结论：在治疗产肺炎克雷伯菌碳青霉烯酶的CRE感染时，头孢他啶 - 阿维巴坦可能是黏菌素的合理替代药物。这些发现需要在随机对照试验中进一步证实。
Background. The efficacy of ceftazidime-avibactam-a cephalosporin-beta-lactamase inhibitor combination with in vitro activity against Klebsiella pneumoniae carbapenemase-producing carbapenem-resistant Enterobacteriaceae (CRE)-compared with colistin remains unknown.Methods. Patients initially treated with either ceftazidime-avibactam or colistin for CRE infections were selected from the Consortium on Resistance Against Carbapenems in Klebsiella and other Enterobacteriaceae (CRACKLE), a prospective, multicenter, observational study. Efficacy, safety, and benefit-risk analyses were performed using intent-to-treat analyses with partial credit and the desirability of outcome ranking approaches. The ordinal efficacy outcome was based on disposition at day 30 after starting treatment (home vs not home but not observed to die in the hospital vs hospital death). All analyses were adjusted for confounding using inverse probability of treatment weighting (IPTW).Results. Thirty-eight patients were treated first with ceftazidime-avibactam and 99 with colistin. Most patients received additional anti-CRE agents as part of their treatment. Bloodstream (n = 63; 46%) and respiratory (n = 30; 22%) infections were most common. In patients treated with ceftazidime-avibactam versus colistin, IPTW-adjusted all-cause hospital mortality 30 days after starting treatment was 9% versus 32%, respectively (difference, 23%; 95% bootstrap confidence interval, 9%-35%; P = .001). In an analysis of disposition at 30 days, patients treated with ceftazidime-avibactam, compared with those treated within colistin, had an IPTW-adjusted probability of a better outcome of 64% (95% confidence interval, 57%-71%). Partial credit analyses indicated uniform superiority of ceftazidime-avibactam to colistin.Conclusions. Ceftazidime-avibactam may be a reasonable alternative to colistin in the treatment of K. pneumoniae carbapenemase- producing CRE infections. These findings require confirmation in a randomized controlled trial.