Heteroresistance to colistin in multidrug-resistant Acinetobacter baumannii
Heteroresistance to colistin in multidrug-resistant Acinetobacter baumannii
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DOI：
10.1128/aac.00103-06
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发表时间：
2006-09-01
影响因子：
4.9
通讯作者：
Liojios, Lisa
中科院分区：
文献类型：
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作者：
Li, Jian;Rayner, Craig R.;Liojios, Lisa
多药耐药鲍曼不动杆菌已经成为世界范围内的一个重要的临床问题，粘菌素正越来越多地被用作“挽救”疗法。粘菌素对鲍曼不动杆菌的最低抑菌浓度(MIC)表明其具有显著的活性。然而，最近有报道称鲍曼不动杆菌对粘菌素具有耐药性。用脉冲场凝胶电泳法测定16株鲍曼不动杆菌临床分离株和ATCC 19606的克隆型，并测定粘菌素MIC值。研究了粘菌素对鲍曼不动杆菌ATCC 19606和临床分离株6的时间杀灭动力学，并进行了种群分析。耐药性的发展是通过连续传代来研究的，无论是否接触粘菌素。在临床分离株中发现了5种不同的PFGE带型。粘菌素对所有菌株的最低抑菌浓度为0.25~2微克/毫升，早期对粘菌素呈浓度依赖性杀灭，24小时后细菌再生长，16株临床分离株中有15株对粘菌素产生异质性耐药。ATCC 19606在10(8)~10(9)cfu/ml的接种量为0.1%，大多数临床分离株在含粘菌素3~10 mU/ml的条件下生长，在含粘菌素的肉汤中连续传代4代(高达200 mU/ml)，能在10 mU g/ml的粘菌素存在下生长的抗性亚群比例从0.000023%增加到100%；即使在无粘菌素的肉汤中传16代后，这一比例也仅下降到2.1%。这是首次在“粘菌素敏感”的临床分离株中发现对粘菌素具有异质性耐药的鲍曼不动杆菌。我们的发现强烈警告说，由于甲磺酸粘菌素某些产品的产品信息中推荐了潜在的次优剂量方案，鲍曼不动杆菌可能会更频繁地出现。
Multidrug-resistant Acinetobacter baumannii has emerged as a significant clinical problem worldwide and colistin is being used increasingly as "salvage" therapy. MICs of colistin against A. baumannii indicate its significant activity. However, resistance to colistin in A. baumannii has been reported recently. Clonotypes of 16 clinical A. baumannii isolates and ATCC 19606 were determined by pulsed-field gel electrophoresis (PFGE), and colistin MICs were measured. The time-kill kinetics of colistin against A. baumannii ATCC 19606 and clinical isolate 6 were investigated, and population analysis profiles (PAPs) were conducted. Resistance development was investigated by serial passaging with or without exposure to colistin. Five different PFGE banding patterns were found in the clinical isolates. MICs of colistin against all isolates were within 0.25 to 2 mu g/ml. Colistin showed early concentration-dependent killing, but bacterial regrowth was observed at 24 h. PAPs revealed that heteroresistance to colistin occurred in 15 of the 16 clinical isolates. Subpopulations (< 0.1% from inocula of 10(8) to 10(9) CFU/ml) of ATCC 19606, and most clinical isolates grew in the presence of colistin 3 to 10 mu g/ml. Four successive passages of ATCC 19606 in broth containing colistin (up to 200 mu g/ml) substantially increased the proportion of the resistant subpopulations able to grow in the presence of colistin at 10 mu g/ml from 0.000023 to 100%; even after 16 passages in colistin-free broth, the proportion only decreased to 2.1%. This represents the first demonstration of heterogeneous colistin-resistant A. baumannii in "colistin-susceptible" clinical isolates. Our findings give a strong warning that colistin-resistant A. baumannii may be observed more frequently due to potential suboptimal dosage regimens recommended in the product information of some products of colistin methanesulfonate.