Graduate Institute of Clinical Medical Sciences, Chang Gung University College of Medicine, Taoyuan, Taiwan.
Int J Antimicrob Agents. 2011 Apr;37(4):302-8. doi: 10.1016/j.ijantimicag.2010.12.015. Epub 2011 Feb 25.
Acinetobacter baumannii has emerged as a major pathogen causing nosocomial infections, particularly in critical patients admitted to the Intensive Care Unit. Increasing resistance to carbapenems in A. baumannii has been observed worldwide. Here we report the clinical impact and mechanism of imipenem heteroresistance (imipenem minimum inhibitory concentration of 6-32 μg/mL with the presence of resistant cells inside the inhibition zone of Etest strips or disks) in multidrug-resistant A. baumannii (MDR-AB). To identify risk factors associated with the emergence of imipenem heteroresistance, a retrospective case-control study was undertaken involving cases with subsequent clinical isolates of the same genotype showing loss of imipenem susceptibility and matched controls with isolates belonging to imipenem-susceptible MDR-AB. The molecular mechanism of heteroresistance was examined. From April 2006 to March 2007, 126 consecutive isolates of MDR-AB were identified from 29 patients. Switch from imipenem susceptibility to heteroresistance was more likely to occur in successive MDR-AB derived from patients who had been exposed to imipenem (length of use 10.9 ± 6.5 days for cases vs. 5.3 ± 4.8 days for controls; P=0.02). An insertion sequence (ISAba1) was found in the promoter region of a class C β-lactamase gene (bla(ADC-29)) in most imipenem-heteroresistant MDR-AB isolates. In vitro experiments indicated that imipenem heteroresistance, which was associated with overexpression of bla(ADC-29), could be induced by imipenem. Carbapenem use was the only risk factor identified for the emergence of carbapenem-heteroresistant MDR-AB. Physicians should weigh the benefits and risks of each carbapenem-based treatment in managing carbapenem-susceptible MDR-AB infection.
鲍曼不动杆菌已成为引起医院感染的主要病原体，尤其是在重症监护病房接受治疗的危重症患者中。目前，在全球范围内都观察到鲍曼不动杆菌对碳青霉烯类药物的耐药性不断增加。在此，我们报告了多重耐药鲍曼不动杆菌（MDR-AB）中碳青霉烯类药物异质性耐药（亚胺培南最低抑菌浓度为 6-32μg/ml，Etest 试条或药敏纸片的抑菌圈内存在耐药细胞）的临床影响和机制。为了确定与亚胺培南异质性耐药出现相关的危险因素，我们进行了一项回顾性病例对照研究，纳入了随后出现相同基因型临床分离株且对亚胺培南敏感性丧失的病例以及对亚胺培南敏感的 MDR-AB 分离株匹配的对照。我们还对异质性耐药的分子机制进行了检测。2006 年 4 月至 2007 年 3 月，从 29 名患者中分离出了 126 株连续的 MDR-AB。与对亚胺培南敏感的 MDR-AB 分离株相比，那些来自先前暴露于亚胺培南（病例组的使用时间为 10.9±6.5 天，对照组为 5.3±4.8 天；P=0.02）的患者的连续 MDR-AB 更有可能从对亚胺培南敏感转为异质性耐药。在大多数对亚胺培南异质性耐药的 MDR-AB 分离株中，发现了插入序列（ISAba1）位于一种 C 类β-内酰胺酶基因（bla（ADC-29））的启动子区域。体外实验表明，与 bla（ADC-29）过表达相关的亚胺培异质性耐药可以被亚胺培南诱导。碳青霉烯类药物的使用是唯一确定的与碳青霉烯类药物异质性耐药的 MDR-AB 出现相关的危险因素。在治疗对碳青霉烯类药物敏感的 MDR-AB 感染时，医生应该权衡每一种碳青霉烯类药物治疗的获益和风险。
