Juscele Felipe, Saidenberg Andre B S, Christoffersen Lars E B, Edslev Sofie M, Hallstrøm Søren, Nacarato Jessica R, Barbosa Fernanda B, Cunha Marcos P, Esposito Fernanda, Lincopan Nilton H, Stegger Marc, Knöbl Terezinha
School of Veterinary Medicine and Animal Science, Universidade de São Paulo, São Paulo 05508-270, Brazil.
Department of Sequencing and Bioinformatics, Statens Serum Institut, 2300 Copenhagen, Denmark.
Antibiotics (Basel). 2025 Mar 6;14(3):269. doi: 10.3390/antibiotics14030269.
: Fosfomycin, a critically important antibiotic, is widely used to treat urinary tract infections (UTIs) caused by multidrug-resistant (MDR) , particularly those producing extended-spectrum β-lactamases (ESBLs). However, its increasing use in livestock has raised concerns about resistance development and global dissemination. This study investigated fosfomycin resistance in isolates from 400 fecal samples collected at Brazilian broiler farms. : The samples were tested for their minimum inhibitory concentration (MIC), screened with PCR for specific resistance genes, and selected isolated were whole genome sequenced. : Phenotypic resistance to fosfomycin was detected in 19% (75/400) of the isolates, while the gene, encoding enzymatic resistance, was identified in 4% (16/400) via PCR screening. Long-read sequencing of seven -positive isolates revealed the presence of on IncFII and IncX plasmids, often co-located with within a conserved 26-flanked transposon. Comparative genomic analysis of 133,541 global genomes from EnteroBase showed that 35% harbored similar transposon structures, with 2% carrying . These -positive isolates were significantly associated with South America and exhibited high co-carriage of ESBL genes, particularly in environmental and poultry-associated isolates. Phylogenetic analysis demonstrated no clustering by host or geographic origin, highlighting the global dissemination of these resistance determinants. : Our findings emphasize the role of poultry production in the spread of fosfomycin and ESBL resistance, driven by transmissible plasmids and co-selection with third-generation cephalosporins. Improved antimicrobial stewardship, surveillance programs, and alternative management strategies are urgently needed to mitigate the dissemination of resistance and preserve fosfomycin's efficacy in human medicine.
磷霉素是一种极其重要的抗生素，广泛用于治疗由多重耐药菌（MDR）引起的尿路感染（UTIs），尤其是那些产生超广谱β-内酰胺酶（ESBLs）的细菌。然而，其在牲畜中的使用日益增加，引发了对耐药性发展和全球传播的担忧。本研究调查了从巴西肉鸡养殖场采集的400份粪便样本中的分离株对磷霉素的耐药情况。：对样本进行最低抑菌浓度（MIC）测试，用PCR筛选特定耐药基因，并对选定的分离株进行全基因组测序。：在19%（75/400）的分离株中检测到对磷霉素的表型耐药，而通过PCR筛选在4%（16/400）的分离株中鉴定出编码酶促耐药的基因。对7株阳性分离株的长读长测序显示，在IncFII和IncX质粒上存在，它们通常与位于保守的26侧翼转座子内的共定位。对来自EnteroBase的133541个全球基因组的比较基因组分析表明，35%的基因组具有相似的转座子结构，2%携带。这些阳性分离株与南美洲显著相关，并表现出ESBL基因的高共携带率，特别是在环境和家禽相关分离株中。系统发育分析表明，不存在按宿主或地理来源的聚类，突出了这些耐药决定因素的全球传播。：我们的研究结果强调了家禽生产在磷霉素和ESBL耐药性传播中的作用，这是由可传播质粒和与第三代头孢菌素的共选择驱动的。迫切需要改进抗菌药物管理、监测计划和替代管理策略，以减轻耐药性的传播并保持磷霉素在人类医学中的疗效。
