Department of Veterinary Medicine, University of Veterinary and Animal Sciences, Lahore, 54000, Pakistan.
Institute of Biochemistry and Biotechnology, University of Veterinary and Animal Sciences, Lahore, 54000, Pakistan.
Microb Pathog. 2022 Oct;171:105691. doi: 10.1016/j.micpath.2022.105691. Epub 2022 Aug 19.
The current study was designed to characterize methicillin-resistant Staphylococcus aureus (MRSA) isolated from bovine milk, along with its response to antibiotics, and ultimately reverse its mechanism of resistance by modulation with non-antibiotics. The synergistic combination of antibiotics with NSAIDs were tested in-vivo by giving MRSA challenge to rabbits. The current study reported an overall 23.79% prevalence of MRSA. The BLAST alignment of current study sequences revealed 99% similarity with mecA gene of MRSA from NCBI database. The current study isolates were more similar to each other and also with reference sequences as compared to other mecA gene sequences from Turkey, India, and Russia. Antibiogram of MRSA isolates showed a highly resistant response to cefoxitin, amoxicillin, and gentamicin. Amoxicillin, gentamicin, tylosin, vancomycin, and ciprofloxacin elicited a significant response (p < 0.05) in combination with non-antibiotics against tested MRSA isolates. The highest zone of inhibition (ZOI) increase was noted for vancomycin in combination with flunixin meglumine (145.45%) and meloxicam (139.36%); gentamicin with flunixin meglumine (85.71%) and ciprofloxacin with ivermectin (71.13%). Synergistic behavior was observed in the combination of gentamicin with ketoprofen; sulfamethoxazole and oxytetracycline with meloxicam. Hematological analysis showed significant differences (p < 0.05) among lymphocyte count and bilirubin. On histopathological examination of skin tissue, hyperplasia of epithelium, sloughed off epidermis, hyperkeratosis, infiltration of inflammatory cells, and hemorrhages were observed. The highest cure rate was observed in case of gentamicin in combination with ketoprofen as compared to other treatment groups. The current study concluded antibiotics in combination with non-antibiotics as potential therapeutic agents for resistance modulation against MRSA. This study will help to devise treatment and control strategies against bovine mastitis. Although the prospect of using NSAIDs to manage infections caused by MRSA appears to be a promising direction, further studies should be conducted to test these medications using suitable in-vivo models in controlled clinical trials to justify their repurposing as a treatment for MRSA infections.
本研究旨在对从牛奶中分离的耐甲氧西林金黄色葡萄球菌（MRSA）进行鉴定，包括其对抗生素的反应，并最终通过非抗生素调节来逆转其耐药机制。通过对兔子进行 MRSA 挑战，测试了抗生素与 NSAIDs 的协同组合。本研究报告的 MRSA 总流行率为 23.79%。当前研究序列的 BLAST 比对显示，与 NCBI 数据库中 MRSA 的 mecA 基因具有 99%的相似性。与来自土耳其、印度和俄罗斯的其他 mecA 基因序列相比，本研究的分离株彼此之间以及与参考序列更为相似。MRSA 分离株的抗生素谱对头孢西丁、阿莫西林和庆大霉素表现出高度耐药反应。阿莫西林、庆大霉素、泰乐菌素、万古霉素和环丙沙星与非抗生素联合使用时，对测试的 MRSA 分离株产生了显著的反应（p<0.05）。联合使用氟尼辛葡甲胺和甲泼尼龙（145.45%）以及美洛昔康（139.36%）时，万古霉素的抑菌圈增加最大；联合使用氟尼辛葡甲胺和庆大霉素（85.71%）以及联合使用伊维菌素和环丙沙星（71.13%）时，庆大霉素的抑菌圈增加最大。联合使用酮洛芬和加替沙星时观察到协同作用；联合使用磺胺甲恶唑和强力霉素和美洛昔康时也观察到协同作用。血液学分析显示淋巴细胞计数和胆红素之间存在显著差异（p<0.05）。皮肤组织的组织病理学检查显示，上皮增生、表皮脱落、角化过度、炎症细胞浸润和出血。与其他治疗组相比，联合使用庆大霉素和酮洛芬的治愈率最高。本研究得出结论，抗生素联合非抗生素可能是调节 MRSA 耐药性的潜在治疗药物。本研究将有助于制定针对牛乳腺炎的治疗和控制策略。虽然使用 NSAIDs 来管理由 MRSA 引起的感染似乎是一个有前途的方向，但应在适当的体内模型中进行进一步的研究，以在对照临床试验中测试这些药物，以证明它们可以重新用于治疗 MRSA 感染。
