Xie Panpan, Zhang Yue, Qin Yanhong, Fang Yun, Yang Ning, Bai Yunbiao, Zhi Shimeng, Niu Wenkai, Wang Fusheng, Yuan Xin
Department of Respiratory and Critical Care Medicine, Senior Department of Infectious Diseases, the Fifth Medical Center of PLA General Hospital, Beijing, China.
The Fifth Clinical Medical College, Anhui Medical University, Hefei, Anhui, China.
Front Cell Infect Microbiol. 2025 Mar 4;15:1496521. doi: 10.3389/fcimb.2025.1496521. eCollection 2025.
is one of the most significant pathogens responsible for respiratory infections in humans. Macrolides are recommended as the first-line treatment for infection. The prevalence of macrolide-resistant has increased significantly in recent decades, particularly in China. The mechanisms of resistance in to macrolides have been extensively studied in pediatric patients. However, a paucity reports regarding the resistance characteristics and mechanisms exhibited in adults. The aim of this study was to elucidate the resistance of to macrolides and the underlying mechanisms in adult patients. Pharyngeal swab specimens were collected from adult patients presenting with subacute cough or community-acquired pneumonia at our hospital from January 2011 to June 2017 to identify and isolate strains. The antimicrobial susceptibility of these isolates to 3 macrolide antibiotics was assessed using broth microdilution method. The genes of macrolide-resistant strains were sequenced, and the presence of target methylation genes (, , and ), efflux pump genes (, , , and ), and the macrolide resistance gene was identified through polymerase chain reaction (PCR) testing. Additionally, MICs were determined with and without the efflux pump inhibitor reserpine. A total of 72 strains were isolated from adult patients, with 41.7% (30/72) exhibiting macrolide resistance. Among the 3 macrolides tested, the 16-membered-ring midecamycin exhibited the greatest activity (MIC: 16 µg/ml) against . All macrolide-resistant strains harbored mutations at the 2063 site in domain V of the gene. Two macrolide-resistant clinical isolates were found to harbor the efflux pump genes and . The efflux pump inhibitor reserpine reduced the MIC for azithromycin in these two strains to a quarter of their original values. In summary, macrolide-resistant is commonly observed among adults in Beijing. Point mutations are the primary mechanism responsible for macrolide resistance in adults with . Additionally, the efflux pump mechanism may contribute partially to this resistance. Midecamycin presents a promising alternative drug for treating infections, particularly in cases of azithromycin-resistant infection in young children.
是导致人类呼吸道感染的最重要病原体之一。大环内酯类药物被推荐作为感染的一线治疗药物。近几十年来，对大环内酯类耐药的患病率显著增加，尤其是在中国。在儿科患者中，对大环内酯类耐药的机制已得到广泛研究。然而，关于成人中表现出的耐药特征和机制的报道很少。本研究的目的是阐明成人患者中对大环内酯类的耐药性及其潜在机制。2011年1月至2017年6月期间，从我院出现亚急性咳嗽或社区获得性肺炎的成年患者中采集咽拭子标本，以鉴定和分离菌株。使用肉汤微量稀释法评估这些分离株对3种大环内酯类抗生素的抗菌敏感性。对大环内酯类耐药菌株的基因进行测序，并通过聚合酶链反应（PCR）检测确定靶甲基化基因（、和）、外排泵基因（、、和）以及大环内酯类耐药基因的存在。此外，在有和没有外排泵抑制剂利血平的情况下测定最低抑菌浓度（MIC）。共从成年患者中分离出72株菌株，其中41.7%（30/72）表现出对大环内酯类耐药。在所测试的3种大环内酯类药物中，16元环麦迪霉素对表现出最大活性（MIC：16μg/ml）。所有大环内酯类耐药菌株在基因V结构域的2063位点均存在突变。发现两株大环内酯类耐药临床分离株携带外排泵基因和。外排泵抑制剂利血平将这两株菌株中阿奇霉素的MIC降低至其原始值的四分之一。总之，在北京的成年人中普遍观察到对大环内酯类耐药的情况。点突变是成人感染中对大环内酯类耐药的主要机制。此外，外排泵机制可能部分导致这种耐药性。麦迪霉素是治疗感染的一种有前景的替代药物，特别是在幼儿阿奇霉素耐药感染的情况下。
