Cheng Aristine, Chuang Yu-Chung, Sun Hsin-Yun, Sheng Wang-Huei, Yang Chia-Jui, Liao Chun-Hsing, Hsueh Po-Ren, Yang Jia-Ling, Shen Ni-Jiin, Wang Jann-Tay, Hung Chien-Ching, Chen Yee-Chun, Chang Shan-Chwen
1Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan. 2Department of Internal Medicine, National Taiwan University Hospital Hsin-chu Branch, Hsin-chu, Taiwan. 3Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan. 4Department of Internal Medicine, Far Eastern Memorial Hospital, New Taipei City, Taiwan. 5Department of Internal Medicine, National Taiwan University Hospital Yun-Lin Branch, Yun-lin, Taiwan. 6Department of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan.
Crit Care Med. 2015 Jun;43(6):1194-204. doi: 10.1097/CCM.0000000000000933.
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.
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.
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).
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.
由于对于广泛耐药鲍曼不动杆菌（全球重症监护病房中一种新出现的威胁）几乎没有治疗选择，且缺乏基于黏菌素的联合疗法的比较性前瞻性研究，我们的目的是比较接受黏菌素 - 碳青霉烯类和黏菌素 - 替加环素联合治疗的广泛耐药鲍曼不动杆菌菌血症患者的治疗结果。
前瞻性、观察性、多中心研究。
地点、患者及干预措施：2010年至2013年期间，在台湾的三家医院对患有广泛耐药鲍曼不动杆菌菌血症的成年人进行前瞻性随访。广泛耐药鲍曼不动杆菌被定义为除黏菌素和替加环素外对所有药物类别均不敏感的鲍曼不动杆菌（基因种2），标准联合疗法为在菌血症发作后至少48小时使用肠外黏菌素 - 碳青霉烯类或黏菌素 - 替加环素。
主要结局指标为14天死亡率。在评估的176例广泛耐药鲍曼不动杆菌菌血症发作中，55例患者（年龄中位数[四分位间距]为62岁[44 - 79岁]，序贯器官衰竭评估评分9分[5 - 13分]）接受了标准联合疗法：29例患者接受黏菌素 - 替加环素治疗，26例患者接受黏菌素 - 碳青霉烯类治疗。接受黏菌素 - 替加环素治疗的患者与接受黏菌素 - 碳青霉烯类治疗的患者的14天粗死亡率分别为35%对15%（p = 0.105），住院死亡率分别为69%对50%（p = 0.152）。黏菌素 - 替加环素组在联合治疗稳态浓度下的突破性广泛耐药鲍曼不动杆菌菌血症发生率为18%，黏菌素 - 碳青霉烯类组为0%（p = 0.059）。11例患者（20.0%）发生肾毒性。在对年龄、性别、合并症、初始疾病严重程度、黏菌素负荷剂量、多微生物感染和原发性感染部位进行调整后，与黏菌素 - 碳青霉烯类治疗相比，在替加环素最低抑菌浓度大于2mg/L的亚组中，使用黏菌素 - 替加环素与14天额外死亡率相关（风险比，6.93；95%CI，1.61 - 29.78；p = 0.009）。
与黏菌素 - 碳青霉烯类治疗广泛耐药鲍曼不动杆菌菌血症相比，当替加环素最低抑菌浓度大于2mg/L时，黏菌素 - 替加环素治疗与14天死亡率增加相关。
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