Pilot Screening to Determine Antimicrobial Synergies in a Multidrug-Resistant Bacterial Strain Library.
Pilot Screening to Determine Antimicrobial Synergies in a Multidrug-Resistant Bacterial Strain Library.
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DOI：
10.1089/mdr.2015.0251
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发表时间：
2016-07
期刊：
影响因子：
--
通讯作者：
Yoo JH
中科院分区：
文献类型：
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作者：
Kim SH;Park C;Chun HS;Lee DG;Choi JK;Lee HJ;Cho SY;Park SH;Choi SM;Choi JH;Yoo JH
随着多重耐药（MDR）细菌感染的增加，人们越来越关注≥2种抗菌药物联合使用的协同作用。我们建立了一个MDR细菌菌株库，通过使用肉汤微量稀释棋盘法和高通量基于内切酶的细菌细胞活力测定来筛选体外抗菌协同作用。总共使用了39株MDR细菌菌株，包括23株碳青霉烯类耐药革兰氏阴性菌、9株万古霉素中间型金黄色葡萄球菌和7株万古霉素耐药粪肠球菌，以筛选潜在的抗菌协同作用。在库中，亚胺培南+甲氧苄啶-磺胺甲恶唑联合用药对碳青霉烯类耐药鲍曼不动杆菌的协同作用更常见。为了验证这一发现，我们测试了34 A。鲍曼不动杆菌临床分离株对亚胺培南和甲氧苄啶-磺胺甲恶唑均耐药。亚胺培南加甲氧苄啶-磺胺甲恶唑联合治疗21例（62%）临床分离株显示出协同作用。结果表明，在MDR细菌菌株库中进行抗菌药物协同作用的初步筛选可能在选择治疗MDR细菌感染的联合治疗方案中具有价值。进一步的研究是必要的，以确定这种筛选系统是否可以用于筛选传统抗菌剂和新一代抗菌剂或非抗菌剂的联合作用。
With the rise in multidrug-resistant (MDR) bacterial infections, there has been increasing interest in combinations of ≥2 antimicrobial agents with synergistic effects. We established an MDR bacterial strain library to screen for in vitro antimicrobial synergy by using a broth microdilution checkerboard method and high-throughput luciferase-based bacterial cell viability assay. In total, 39 MDR bacterial strains, including 23 carbapenem-resistant gram-negative bacteria, 9 vancomycin-intermediate Staphylococcus aureus, and 7 vancomycin-resistant Enterococcus faecalis, were used to screen for potential antimicrobial synergies. Synergies were more frequently identified with combinations of imipenem plus trimethoprim–sulfamethoxazole for carbapenem-resistant Acinetobacter baumannii in the library. To verify this finding, we tested 34 A. baumannii clinical isolates resistant to both imipenem and trimethoprim–sulfamethoxazole by the checkerboard method. The imipenem plus trimethoprim–sulfamethoxazole combination showed synergy in the treatment of 21 (62%) of the clinical isolates. The results indicate that pilot screening for antimicrobial synergy in the MDR bacterial strain library could be valuable in the selection of combination therapeutic regimens to treat MDR bacterial infections. Further studies are warranted to determine whether this screening system can be useful to screen for the combined effects of conventional antimicrobials and new-generation antimicrobials or nonantimicrobials.