Swinkels Aram F, Fischer Egil A J, Korving Lisa, Christodoulou Rafaella, Wagenaar Jaap A, Zomer Aldert L
Faculty of Veterinary Medicine, Division of Infectious Diseases and Immunology, Utrecht University, Utrecht, The Netherlands.
Department of Population Health Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
NPJ Antimicrob Resist. 2024 Oct 3;2(1):28. doi: 10.1038/s44259-024-00044-5.
Fluoroquinolone resistance in E. coli isolates from livestock in Europe remains high despite EMA restrictions on fluoroquinolone use in animals. However, flumequine, a quinolone not classified as a fluoroquinolone by various regulatory bodies, is still used in livestock in the Netherlands, Belgium, Greece and France. We investigated whether flumequine selects for the same resistance mechanisms in E. coli. Resistant and non-resistant E. coli isolates were obtained from caecal fermentation assays and broilers exposed to concentrations of flumequine and enrofloxacin. Flumequine usage leads to an approximately 3-fold increase in resistant E. coli in the caecal fermentation, similar to enrofloxacin. In vitro exposure to both flumequine and enrofloxacin revealed the same amino acid substitutions (S83L, D87G) in GyrA. Additionally, the same resistance-causing substitutions were found in phenotypically resistant E. coli isolates from broilers treated with either enrofloxacin or flumequine. Flumequine induces similar resistance mechanisms as enrofloxacin, warranting equivalent restrictions on its use.
尽管欧洲药品管理局（EMA）对动物使用氟喹诺酮类药物有所限制，但欧洲家畜源大肠杆菌分离株对氟喹诺酮类药物的耐药性仍然很高。然而，氟甲喹这种未被各监管机构归类为氟喹诺酮类的喹诺酮，仍在荷兰、比利时、希腊和法国的家畜中使用。我们研究了氟甲喹是否会在大肠杆菌中选择相同的耐药机制。通过盲肠发酵试验以及暴露于氟甲喹和恩诺沙星浓度下的肉鸡获得了耐药和非耐药的大肠杆菌分离株。氟甲喹的使用导致盲肠发酵中耐药大肠杆菌增加约3倍，与恩诺沙星相似。体外暴露于氟甲喹和恩诺沙星均显示在GyrA中出现相同的氨基酸取代（S83L、D87G）。此外，在用恩诺沙星或氟甲喹治疗的肉鸡的表型耐药大肠杆菌分离株中也发现了相同的导致耐药的取代。氟甲喹诱导的耐药机制与恩诺沙星相似，因此有必要对其使用进行同等限制。
