Wang Yang, Wu Cong-Ming, Lu Li-Ming, Ren Gao-Wa Na, Cao Xing-Yuan, Shen Jian-Zhong
Department of Pharmacology and Toxicology, College of Veterinary Medicine, China Agricultural University, Beijing 100094, People's Republic of China.
Vet Microbiol. 2008 Jul 27;130(1-2):118-25. doi: 10.1016/j.vetmic.2007.12.012. Epub 2008 Jan 3.
The present study aimed to determine the prevalence and mechanisms of macrolide-lincosamide (ML) resistance in 72 Staphylococcus aureus isolates from cows with clinical mastitis. Minimum inhibitory concentrations (MIC) of ML antibiotics were determined by the broth microdilution technique, inducible ML resistance phenotype by the D test, and ML resistance genes by PCR assay. The isolates showed a high level of resistance to erythromycin (93.1%), azithromycin (93.1%), spiramycin (41.7%), tylosin (40.3%), tilmicosin (27.8%), and clindamycin (36.1%). Macrolide-lincosamide MIC(90) values were > or = 128 mg/L. Inducible ML resistance (iML) phenotype was detected in 52.8% (38/72) of isolates. In erythromycin-resistant (ER-R) strains, methylase genes ermB and ermC, efflux gene msrA/msrB, and inactivating enzyme genes lnuA and mphC were present alone or in various combinations, with ermB and ermC genes predominating. This is the first report of ML resistance genes ermB, mrsA/mrsB and mphC in S. aureus isolated from bovine mastitis. The occurrence of high levels of resistance to ML antibiotics among the S. aureus isolates, and the high rate of iML phenotype, indicate that appropriate alternative antibiotics should be prescribed for treating bovine mastitis caused by S. aureus. Furthermore, significant differences in the conformations of lactone rings of 16- and 14-membered macrolides could explain why some isolates with a constitutive ML resistance (cML) phenotype were sensitive to 16-membered macrolides alone. The different interaction of the 16-membered macrolides with the 50S ribosomal subunit is also presumably the reason why the susceptibility results of tilmcosin differed from those of tylosin and spiramycin.
本研究旨在确定从患有临床乳腺炎的奶牛中分离出的72株金黄色葡萄球菌对大环内酯-林可酰胺类（ML）抗生素耐药的发生率及机制。采用肉汤微量稀释技术测定ML抗生素的最低抑菌浓度（MIC），通过D试验检测可诱导ML耐药表型，采用聚合酶链反应（PCR）检测ML耐药基因。分离株对红霉素（93.1%）、阿奇霉素（93.1%）、螺旋霉素（41.7%）、泰乐菌素（40.3%）、替米考星（27.8%）和克林霉素（36.1%）表现出高水平耐药。大环内酯-林可酰胺类MIC（90）值≥128mg/L。在52.8%（38/72）的分离株中检测到可诱导ML耐药（iML）表型。在耐红霉素（ER-R）菌株中，甲基化酶基因ermB和ermC、外排基因msrA/msrB以及灭活酶基因lnuA和mphC单独或多种组合存在，其中ermB和ermC基因占主导。这是首次报道从牛乳腺炎分离出的金黄色葡萄球菌中存在ML耐药基因ermB、mrsA/mrsB和mphC。金黄色葡萄球菌分离株中对ML抗生素的高水平耐药以及iML表型的高发生率表明，治疗由金黄色葡萄球菌引起的牛乳腺炎应选用合适的替代抗生素。此外，16元环和14元环大环内酯内酯环构象的显著差异可以解释为什么一些具有组成型ML耐药（cML）表型的分离株仅对16元环大环内酯敏感。16元环大环内酯与50S核糖体亚基的不同相互作用也可能是替米考星药敏结果与泰乐菌素和螺旋霉素不同的原因。
