Excess Mortality Associated With Colistin-Tigecycline Compared With Colistin-Carbapenem Combination Therapy for Extensively Drug-Resistant Acinetobacter baumannii Bacteremia: A Multicenter Prospective Observational Study
Excess Mortality Associated With Colistin-Tigecycline Compared With Colistin-Carbapenem Combination Therapy for Extensively Drug-Resistant Acinetobacter baumannii Bacteremia: A Multicenter Prospective Observational Study
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DOI：
10.1097/ccm.0000000000000933
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发表时间：
2015-06-01
影响因子：
8.8
通讯作者：
Chang, Shan-Chwen
中科院分区：
文献类型：
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作者：
Cheng, Aristine;Chuang, Yu-Chung;Chang, Shan-Chwen
目的：由于广泛耐药鲍曼不动杆菌是全球ICU的新威胁，治疗选择很少，并且缺乏基于粘菌素的联合治疗的前瞻性比较研究，我们的目的是比较广泛耐药鲍曼不动杆菌患者的结局。设计：前瞻性、观察性、多中心研究。2010年至2013年，在台湾的三家医院前瞻性随访了鲍曼菌血症。广泛耐药A.鲍曼不动杆菌定义为A.鲍曼不动杆菌（基因种2）对除粘菌素和替加环素以外的所有药物类别不敏感，并且在菌血症发作后至少48小时内使用胃肠外粘菌素-碳青霉烯或粘菌素-替加环素的标准组合疗法。在176例广泛耐药A。在评估鲍曼不动杆菌血症时，55名中位（四分位距）年龄为62岁（44-79岁）且序贯器官衰竭评估评分为9（5-13）分的患者接受标准组合疗法：29名患者接受粘菌素-替加环素，26名患者接受粘菌素-碳青霉烯。接受粘菌素-替加环素治疗的患者与接受粘菌素-碳青霉烯治疗的患者的14天和住院期间粗死亡率分别为35%和15%（p = 0.105）以及69%和50%（p = 0.152）。突破广泛耐药A.在联合治疗的稳态浓度下，粘菌素-替加环素组的鲍曼菌血症为18%，而粘菌素-碳青霉烯组为0%（p = 0.059）。11例患者（20.0%）发生肾毒性。在调整了年龄、性别、合并症、初始疾病严重程度、负荷粘菌素剂量、多种微生物感染和原发感染部位后，与使用粘菌素-碳青霉烯相比，在替加环素最低抑菌浓度大于2 mg/L的亚组中，使用粘菌素-替加环素与14天死亡率相关结论：与粘菌素-碳青霉烯治疗广泛耐药的A.鲍曼氏菌血症
Objectives: Since few therapeutic options exist for extensively drug resistant Acinetobacter baumannii, an emerging threat in ICUs worldwide, and comparative prospective studies of colistin-based combination therapies are lacking, our objective was to compare the outcomes of patients with extensively drug-resistant A. baumannii bacteremia, treated with colistin-carbapenem and colistin-tigecycline combinations.Design: Prospective, observational, multicenter study.Setting, Patients, and Interventions: Adults with extensively drug-resistant A. baumannii bacteremia were prospectively followed from 2010 to 2013 at three hospitals in Taiwan. Extensively drug-resistant A. baumannii was defined as A. baumannii (genospecies 2) nonsusceptible to all drug classes except for colistin and tigecycline, and standard combination therapy as use of parenteral colistin-carbapenem or colistin-tigecycline for at least 48 hours after onset of bacteremia.Measurements and Main Results: Primary outcome measure was 14-day mortality. Of the 176 episodes of extensively drug-resistant A. baumannii bacteremia evaluated, 55 patients with a median (interquartile range) age of 62 years (44-79 yr) and Sequential Organ Failure Assessment score of 9 (5-13) points received standard combination therapy: colistin-tigecycline in 29 patients and colistin-carbapenem in 26. Crude 14-day and in-hospital mortality rates for patients receiving colistin-tigecycline versus patients receiving colistin-carbapenem were 35% versus 15% (p = 0.105) and 69% versus 50% (p = 0.152), respectively. Breakthrough extensively drug-resistant A. baumannii bacteremia under steady state concentrations of combination therapy for colistin-tigecycline group was 18% and for colistin-carbapenem group was 0% (p = 0.059). Eleven patients (20.0%) developed nephrotoxicity. After adjusting for age, sex, comorbidity, initial disease severity, loading colistin dose, polymicrobial infection, and primary infection site, excess 14-day mortality was associated with the use of colistin-tigecycline in the subgroup with tigecycline minimum inhibitory concentration greater than 2 mg/L compared with the use of colistin-carbapenem (hazard ratio, 6.93; 95% CI, 1.61-29.78; p = 0.009).Conclusions: Increased 14-day mortality was associated with colistin-tigecycline therapy given tigecycline minimum inhibitory concentration greater than 2 mg/L compared with colistin-carbapenem therapy for extensively drug-resistant A. baumannii bacteremia.