BACKGROUND Among all cases of nosocomial pneumonia, Staphylococcus aureus is the second most prevalent pathogen (17.8%). In Europe, 29.9% of the isolates are oxacillin-resistant. The changing epidemiology of methicillin-resistant Staphylococcus aureus (MRSA) nosocomial infections and the decreasing susceptibility to first-line antibiotics leave clinicians with few therapeutic options. The objective of our study was to determine the antimicrobial susceptibility, the associated molecular mechanisms of resistance and the epidemiological relatedness of MRSA strains isolated from the endotracheal tubes (ETT) of intubated critically ill patients in the intensive care unit (ICU) with nosocomial pneumonia caused by Staphylococcus aureus. METHODS The antimicrobial susceptibility to vancomycin, linezolid, ciprofloxacin, clindamycin, erythromycin, chloramphenicol, fusidic acid, gentamicin, quinupristin-dalfopristin, rifampicin, sulfamethoxazole/trimethoprim, and tetracycline were measured. Resistance mechanisms were then analyzed by polymerase chain reaction and sequencing. Molecular epidemiology was carried out by multi-locus sequence typing. RESULTS S. aureus isolates were resistant to ciprofloxacin, erythromycin, gentamicin, tetracycline, clindamycin, and fusidic acid. The most frequent mutations in quinolone-resistant S. aureus strains were S84L in the gyrA gene, V511A in the gyrB gene, S144P in the grlA gene, and K401R/E in the grlB gene. Strains resistant to erythromycin carried the ermC, ermA, and msrA genes; the same ermC and ermA genes were detected in strains resistant to clindamycin. The aac(6')-aph(2″) gene was related to gentamicin resistance, while resistance to tetracycline was related to tetK (efflux pump). The fusB gene was detected in the strain resistant to fusidic acid. The most frequent sequence types were ST22, ST8, and ST217, which were distributed in four clonal complexes (CC5, CC22, CC45, and CC59). CONCLUSIONS High levels of resistance to second-line antimicrobials threatens the treatment of nosocomial respiratory infections due to methicillin-resistant S. aureus with decreased susceptibility to linezolid and vancomycin. The wide genotypic diversity found reinforces the central role of ICU infection control in preventing nosocomial transmission.

中文翻译：

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医院肺炎患者气管插管中耐甲氧西林金黄色葡萄球菌临床菌株的分子特征。


背景 在所有院内肺炎病例中，金黄色葡萄球菌是第二常见的病原体（17.8%）。在欧洲，29.9% 的分离株对苯唑西林具有耐药性。耐甲氧西林金黄色葡萄球菌 (MRSA) 院内感染流行病学的变化以及一线抗生素敏感性的降低使得临床医生几乎没有治疗选择。我们研究的目的是确定从重症监护病房 (ICU) 气管插管 (ETT) 中分离的 MRSA 菌株的抗菌药物敏感性、相关耐药分子机制和流行病学相关性。由金黄色葡萄球菌引起。方法测定万古霉素、利奈唑胺、环丙沙星、克林霉素、红霉素、氯霉素、夫西地酸、庆大霉素、奎奴普丁-达福普汀、利福平、磺胺甲恶唑/甲氧苄啶、四环素的敏感性。然后通过聚合酶链反应和测序分析耐药机制。通过多位点序列分型进行分子流行病学研究。结果 金黄色葡萄球菌分离株对环丙沙星、红霉素、庆大霉素、四环素、克林霉素和夫西地酸耐药。喹诺酮抗性金黄色葡萄球菌菌株中最常见的突变是gyrA基因中的S84L、gyrB基因中的V511A、grlA基因中的S144P和grlB基因中的K401R/E。对红霉素耐药的菌株携带 ermC、ermA 和 msrA 基因；在克林霉素耐药菌株中检测到相同的 ermC 和 ermA 基因。 aac(6')-aph(2″)基因与庆大霉素耐药相关，而四环素耐药与tetK（外排泵）相关。 在夫西地酸耐药菌株中检测到fusB基因。最常见的序列类型是 ST22、ST8 和 ST217，分布在四个克隆复合体（CC5、CC22、CC45 和 CC59）中。结论 由于耐甲氧西林金黄色葡萄球菌对利奈唑胺和万古霉素的敏感性降低，对二线抗菌药物的高耐药性威胁着院内呼吸道感染的治疗。发现的广泛基因型多样性强化了 ICU 感染控制在预防院内传播方面的核心作用。