Antibiotic combinations for controlling colistin-resistant Enterobacter cloacae
Antibiotic combinations for controlling colistin-resistant Enterobacter cloacae
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DOI：
10.1038/ja.2016.77
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发表时间：
2017-02-01
影响因子：
3.3
通讯作者：
Franco, Octavio Luiz
中科院分区：
文献类型：
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作者：
Lima, Thais Bergamin;Silva, Osmar Nascimento;Franco, Octavio Luiz
阴沟肠杆菌是一种革兰氏阴性菌，由于其对多种抗生素的耐药性，与重症监护患者的高发病率和死亡率相关。目前，针对多重耐药细菌的治疗包括使用粘菌素，尽管其在较高浓度下具有毒性作用。在此背景下，粘菌素耐药E.用较低水平的粘菌素与其它抗生素联合攻击梭菌菌株，以减少粘菌素相关的副作用。耐多粘菌素E.通过在亚抑制性粘菌素浓度下连续繁殖来产生梭菌（ATCC 49141）菌株。在此之后，分离三个粘菌素抗性和三个非抗性重复。通过MALDI-TOF MS、VITEK 2和MicroScan分析确认所有菌株的身份。此外，还通过纸片扩散和自动化系统检查了对其他抗生素的交叉耐药性。采用肉汤微量稀释棋盘法观察了粘菌素与氯霉素联合应用的协同作用。首先，本文报道的数据表明，所有菌株对青霉素、头孢菌素（第四代除外）、单环β-内酰胺类抗生素以及青霉素和Ⅱ-内酰胺酶抑制剂的某些联合体均呈现内在耐药性。此外，氯霉素和粘杆菌素组合能够抑制诱导的粘杆菌素耐药菌株以及两种粘杆菌素耐药临床菌株。此外，通过使用这些浓度未观察到细胞毒性作用。总之，本文报道的数据首次显示了粘菌素-氯霉素对粘菌素耐药大肠杆菌引起的感染的可能治疗用途。clothing.
Enterobacter cloacae is a Gram-negative bacterium associated with high morbidity and mortality in intensive care patients due to its resistance to multiple antibiotics. Currently, therapy against multi-resistant bacteria consists of using colistin, in spite of its toxic effects at higher concentrations. In this context, colistin-resistant E. cloacae strains were challenged with lower levels of colistin combined with other antibiotics to reduce colistin-associated side effects. Colistin-resistant E. cloacae (ATCC 49141) strains were generated by serial propagation in subinhibitory colistin concentrations. After this, three colistin-resistant and three nonresistant replicates were isolated. The identity of all the strains was confirmed by MALDI-TOF MS, VITEK 2 and MicroScan analysis. Furthermore, cross-resistance to other antibiotics was checked by disk diffusion and automated systems. The synergistic effects of the combined use of colistin and chloramphenicol were observed via the broth microdilution checkerboard method. First, data here reported showed that all strains presented intrinsic resistance to penicillin, cephalosporin (except fourth generation), monobactam, and some associations of penicillin and ii-lactamase inhibitors. Moreover, a chloramphenicol and colistin combination was capable of inhibiting the induced colistin-resistant strains as well as two colistin-resistant clinical strains. Furthermore, no cytotoxic effect was observed by using such concentrations. In summary, the data reported here showed for the first time the possible therapeutic use of colistin-chloramphenicol for infections caused by colistin-resistant E. cloacae.