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评估磷霉素联合万古霉素对耐万古霉素凝固酶阴性葡萄球菌的作用。

Evaluation of fosfomycin combined with vancomycin against vancomycin-resistant coagulase negative staphylococci.

机构信息

Department of Microbiology, General Division of Basic Medical Sciences, National Organization for Drug Control and Research (NODCAR), Giza, Egypt.

出版信息

J Chemother. 2020 Dec;32(8):411-419. doi: 10.1080/1120009X.2020.1761638. Epub 2020 May 6.

DOI:10.1080/1120009X.2020.1761638
PMID:32372690
Abstract

The pathogenic potential of coagulase-negative staphylococci (CoNS) is increasingly recognized worldwide. The aim of the present study was to evaluate different combinations of fosfomycin (FOS) with vancomycin (VAN) or oxacillin (OXA) against vancomycin-resistant clinical isolates of CoNS. Characterization of VAN resistance in selected isolates was also sought. Antibiotic susceptibility of isolates was tested by disc diffusion method, MICs of antibiotics were determined by the agar dilution method, and fosfomycin combinations were evaluated by a time-kill assay according to the guidelines of the CLSI. Moreover, oxacillin and glycopeptides (vancomycin and teichoplanin) resistances were also characterized phenotypically and genotypically in this study. Out of 258 staphylococci, 52 were CoNS (20.2%). All isolates were multidrug resistant with 75% (n = 39) oxacillin-resistant, most of them with oxacillin MIC levels of >32 mg/L. Moreover, vancomycin non-susceptibility was observed in 46.2% (n = 24) of the tested isolates with MIC range of 4-32 mg/L. Identification of selected isolates revealed that was the most abundant among tested CoNS, followed by , , and interestingly Furthermore, Synergistic and bactericidal effects of FOS + VAN combination were observed in 3 of 9 isolates after 6 h of treatment and in all studied isolates at 24 h. On the other hand, FOS + OXA combinations were ineffective. This study provides evidence that fosfomycin combination with vancomycin could be considered as a therapeutic alternative for CoNS infections. It also sheds some light on the possible emergence of the otherwise harmless bacterium as a human pathogen.

摘要

凝固酶阴性葡萄球菌(CoNS)的致病性在全球范围内日益受到关注。本研究旨在评估磷霉素(FOS)与万古霉素(VAN)或苯唑西林(OXA)联合应用对耐万古霉素CoNS 临床分离株的作用。同时还对部分分离株的万古霉素耐药性特征进行了研究。采用纸片扩散法检测分离株的抗生素敏感性,琼脂稀释法测定抗生素 MIC 值,根据 CLSI 指南进行时间杀伤试验评估 FOS 联合用药方案。此外,本研究还对耐苯唑西林和糖肽类(万古霉素和替考拉宁)表型和基因型进行了特征分析。在 258 株葡萄球菌中,CoNS 为 52 株(20.2%)。所有分离株均为多重耐药株,其中 75%(n=39)为耐苯唑西林株,大多数耐苯唑西林株的苯唑西林 MIC 值>32mg/L。此外,46.2%(n=24)的受试分离株对万古霉素不敏感,MIC 值范围为 4-32mg/L。对部分分离株的鉴定结果显示, 是检测到的 CoNS 中最丰富的菌种,其次是 、 ,有趣的是还有 。经过 6 小时治疗后,FOS+VAN 联合方案在 3 株(9 株中的 3 株)分离株中表现出协同和杀菌作用,在所有研究的分离株中在 24 小时时均表现出协同和杀菌作用。另一方面,FOS+OXA 联合方案无效。本研究为 FOS 联合万古霉素治疗 CoNS 感染提供了依据,同时也表明了原本无害的 可能成为人类病原体。

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