Azithromycin resistance levels and mechanisms in Escherichia coli
Azithromycin resistance levels and mechanisms in Escherichia coli
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DOI：
10.1038/s41598-019-42423-3
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发表时间：
2019-04-15
影响因子：
4.6
通讯作者：
Ruiz, Joaquim
中科院分区：
文献类型：
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作者：
Gomes, Claudia;Ruiz-Roldan, Lidia;Ruiz, Joaquim
尽管阿奇霉素在一些国家被用来治疗由革兰氏阴性病原体引起的感染，但不存在大肠杆菌的耐药临界点。本研究的目的是分析大肠埃希菌对阿奇霉素的耐药性水平及其机制。检测了343株大肠埃希菌的染色体(rplD、rplV和23S rRNA)突变、10个大环内酯类耐药基因(MRGs)和外排泵的高表达。总体而言，(25.9%)分离株对阿奇霉素的MICs和Gt；=32 mg/L，在苯丙氨酸-精氨酸β-萘酰胺存在下，MIC和Gt；降至42株(12.2%)，其中35株至少有一种MRG。外排泵在阿奇霉素耐药中起作用，影响91.2%的分离株的最低抑菌浓度(MIC)水平，而染色体改变的作用似乎很小。在22.7%的分离株中至少发现一种MRG，其中mph(A)是最常见的基因。Mph(A)基因在阿奇霉素耐药中起主要作用，93%携带mph(A)基因的菌株的MIC值为32 mg/L，在缺乏特异性耐药断裂点的情况下，建议将MIC值定为32 mg/L，以检测携带阿奇霉素耐药机制的菌株。
Despite azithromycin being used in some countries to treat infections caused by Gram-negative pathogens, no resistance breakpoint for Escherichia coli exists. The aim of this study was to analyse the levels and mechanisms of azithromycin resistance in E. coli. The presence of chromosomal (rplD, rplV and 23S rRNA) mutations, 10 macrolide resistance genes (MRGs) and efflux pump overexpression was determined in 343 E. coli isolates. Overall, 89 (25.9%) isolates had MICs >= 32 mg/L to azithromycin, decreasing to 42 (12.2%) when assayed in the presence of Phe-Arg-beta-Napthylamide, with 35 of these 42 possessing at least one MRG. Efflux pumps played a role in azithromycin resistance affecting the Minimal Inhibitory Concentration (MIC) levels of 91.2% isolates whereas chromosomal alterations seem to have a minimal role. At least one MRG was found in 22.7% of the isolates with mph(A) being the most commonly found gene. The mph(A) gene plays the main role in the development of azithromycin resistance and 93% of the mph(A)-carrying isolates showed a MIC of 32 mg/L. In the absence of a specific resistance breakpoint our results suggest a MIC of 32 mg/L to be considered in order to detect isolates carrying mechanisms able to confer azithromycin resistance.