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在黎巴嫩家禽中分离的产 ESBL/AmpC 酶大肠杆菌中黏菌素耐药基因和其他抗生素耐药基因的流行情况:一项全国性调查。

Occurrence of the Colistin Resistance Gene and Additional Antibiotic Resistance Genes in ESBL/AmpC-Producing Escherichia coli from Poultry in Lebanon: A Nationwide Survey.

机构信息

ISP, Institut National de Recherche pour l'Agriculture, l'Alimentation, l'Environnement, Université de Tours, Nouzilly, France.

Laboratoire des Agents Pathogènes, Faculté de Pharmacie, Université Saint Joseph de Beyrouth, Beirut, Lebanon.

出版信息

Microbiol Spectr. 2021 Oct 31;9(2):e0002521. doi: 10.1128/Spectrum.00025-21. Epub 2021 Sep 8.

DOI:10.1128/Spectrum.00025-21
PMID:34494875
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8557922/
Abstract

The objective of the present study was to determine genomic characteristics of expanded-spectrum cephalosporin (ESC)-resistant Escherichia coli spreading in healthy broilers in Lebanon in 2018. Rectal swabs ( = 280) from 56 farms were screened for the presence of ESC-resistant E. coli isolates. Antimicrobial susceptibility and extended-spectrum β-lactamase (ESBL)/AmpC production were determined by the disk diffusion method. Whole-genome sequencing (WGS) of 102 representative isolates of E. coli was performed to determine their phylogenetic diversity, serotypes, sequence types (ST), acquired resistance genes, and virulence-associated genes. Fifty-two out of 56 farms housed broilers carrying ESC-resistant E. coli isolates. These farms had large and recurrent antimicrobial practices, using, for some of them, critically important antibiotics for prophylactic and therapeutic purposes. Among the 102 sequenced multidrug-resistant (MDR) E. coli isolates, the proportion of ESBL, plasmid-mediated AmpC β-lactamase (pAmpC) producers, and ESBL/pAmpC coproducers was 60%, 27.6%, and 12.4%, respectively. The most prevalent ESBL/pAmpC genes were , , , , and ( = 42, = 31, =15, = 9, and = 7, respectively). These ESBL/pAmpC producers were distributed in different STs, most being well-known avian-associated and sometimes pathogenic STs (ST-10, ST-48, ST-93, ST-115, ST-117, and ST-457). Phylogenetic single nucleotide polymorphism (SNP) analysis confirmed their genetic diversity and wide dispersion across the Lebanese territory. Most isolates were also resistant to ciprofloxacin (101/102 with 3 QRDR mutations), and 19/102 isolates from 11 unrelated STs also carried the mobile resistance gene . This survey illustrates the alarming prevalence of MDR E. coli resistant to medically important antibiotics in broilers in Lebanon. This advocates the need for surveillance programs of antimicrobial resistance in Lebanon and the reduction of excessive use of antibiotics to limit the spread of MDR E. coli in food-producing animals. Poultry production is a main contributor of the global trend of antimicrobial resistance arising from food-producing animals worldwide. In Lebanon, inappropriate use of antibiotics is frequent in chickens for prophylactic reasons and to improve productivity, resulting in an alarming prevalence of extended-spectrum β-lactamase (ESBL)/AmpC-producing Escherichia coli, also resistant to other medically important antibiotics (i.e., colistin and ciprofloxacin). Their complex genomic epidemiology highlighted by an important genetic diversity suggests that these resistance determinants are largely spreading in enteric bacteria in Lebanese poultry. Further molecular surveillance is needed to understand the country-specific epidemiology of ESBL/AmpC and genes in Lebanese poultry production. In addition, decisive interventions are urgently needed in order to ban the use of critically important antibiotics for human medicine in food-producing animals and limit the spread of antibiotic resistance in Lebanon.

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f01/8557922/cfb01cdfc1d7/spectrum.00025-21-f004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f01/8557922/e39d34d44553/spectrum.00025-21-f001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f01/8557922/f1e0dde6d5c0/spectrum.00025-21-f002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f01/8557922/a979536d631d/spectrum.00025-21-f003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f01/8557922/cfb01cdfc1d7/spectrum.00025-21-f004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f01/8557922/e39d34d44553/spectrum.00025-21-f001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f01/8557922/f1e0dde6d5c0/spectrum.00025-21-f002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f01/8557922/a979536d631d/spectrum.00025-21-f003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f01/8557922/cfb01cdfc1d7/spectrum.00025-21-f004.jpg
摘要

本研究旨在确定 2018 年在黎巴嫩健康肉鸡中传播的耐扩展谱头孢菌素(ESC)的大肠杆菌的基因组特征。从 56 个农场采集 280 份直肠拭子,以筛选 ESC 耐药大肠杆菌分离株。采用纸片扩散法测定抗菌药物敏感性和超广谱β-内酰胺酶(ESBL)/AmpC 的产生情况。对 102 株代表性大肠杆菌分离株进行全基因组测序(WGS),以确定其系统发育多样性、血清型、序列类型(ST)、获得性耐药基因和毒力相关基因。56 个农场中有 52 个农场饲养携带 ESC 耐药大肠杆菌分离株的肉鸡。这些农场经常进行大规模的、反复的抗菌药物治疗,其中一些农场使用了重要的抗生素,包括预防性和治疗性抗生素。在 102 株测序的多药耐药(MDR)大肠杆菌分离株中,ESBL、质粒介导的 AmpCβ-内酰胺酶(pAmpC)产生菌和 ESBL/pAmpC 共产生菌的比例分别为 60%、27.6%和 12.4%。最常见的 ESBL/pAmpC 基因分别为 blaCTX-M-15、blaDHA-1、blaCMY-2、blaCTX-M-14 和 blaCTX-M-3。这些 ESBL/pAmpC 产生菌分布在不同的 ST 中,其中大多数为众所周知的禽源菌,有时是致病性 ST(ST-10、ST-48、ST-93、ST-115、ST-117 和 ST-457)。单核苷酸多态性(SNP)分析证实了它们的遗传多样性和在黎巴嫩领土上的广泛分布。大多数分离株也对环丙沙星耐药(102 株中有 3 株存在 QRDR 突变),11 个无关 ST 的 19 株分离株也携带移动耐药基因 blaCTX-M-15。本研究表明,耐重要抗菌药物的多药耐药大肠杆菌在黎巴嫩肉鸡中非常普遍。这表明有必要在黎巴嫩开展抗菌药物耐药性监测计划,并减少抗生素的过度使用,以限制 MDR 大肠杆菌在食用动物中的传播。家禽生产是全球范围内因食用动物产生的抗菌药物耐药性趋势的主要原因之一。在黎巴嫩,由于预防性原因和提高生产力,经常在鸡中不恰当地使用抗生素,导致广泛存在耐扩展谱β-内酰胺酶(ESBL)/AmpC 的大肠杆菌,也对其他重要的抗菌药物(即黏菌素和环丙沙星)耐药。这些耐药决定因素的复杂基因组流行病学突出了其很大程度上在黎巴嫩家禽肠道细菌中传播的情况。需要进一步的分子监测,以了解黎巴嫩家禽生产中 ESBL/AmpC 和 基因的特定于国家的流行情况。此外,迫切需要采取果断措施,禁止在食用动物中使用对人类医学至关重要的抗生素,并限制抗生素耐药性在黎巴嫩的传播。

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