Table_2_Molecular Characterization of Extended-Spectrum β-Lactamase–Producing Escherichia coli and Klebsiella pneumoniae Among the Pediatric Population in Qatar.DOCX

IntroductionAlthough extended-spectrum β-lactamase (ESBL)–producing Enterobacterales are a public health problem in the Arabian Peninsula, data on the molecular characteristic of their antimicrobial resistance determinants in children is limited.AimTo determine the molecular characteristics of ESBL-producing Escherichia coli and Klebsiella pneumoniae in the pediatric population of Qatar.MethodsWhole-genome sequencing was performed on ESBL-producing E. coli and K. pneumoniae isolates recovered from screening and clinical specimens from pediatric patients at Sidra Medicine in Doha from January to December 2018.ResultsA total of 327 ESBL producers were sequenced: 254 E. coli and 73 K. pneumoniae. Non-susceptibility rates to non-β-lactam antibiotics for both species were 18.1 and 30.1% for gentamicin, 0.8 and 4.1% for amikacin, 41.3 and 41.1% for ciprofloxacin, and 65.8 and 76.1% for cotrimoxazole. The most common sequence types (STs) were ST131 (16.9%), ST38 and ST10 (8.2% each) in E. coli and ST307 (9.7%), and ST45 and ST268 (6.9% each) in K. pneumoniae. CTX-M type ESBLs were found in all but one isolate, with CTX-M-15 accounting for 87.8%. Among other β-lactamases, TEM-1B and OXA-1 were coproduced in 41 and 19.6% of isolates. The most common plasmid-mediated quinolone resistance genes cocarried were qnr A/B/E/S (45.3%). Ninety percent of gentamicin non-susceptible isolates harbored genes encoding AAC(3) enzymes, mainly aac(3)-IIa. Only two of 57 isolates harboring aac(6′)-Ib-cr were non-susceptible to amikacin. Chromosomal mutations in genes encoding DNA gyrase and topoisomerase IV enzymes were detected in 96.2% fluoroquinolone-non-susceptible E. coli and 26.7% fluoroquinolone-non-susceptible K. pneumoniae.ConclusionOur data show that CTX-M enzymes are largely the most prevalent ESBLs in children in Qatar with a predominance of CTX-M-15. Carbapenem-sparing options to treat ESBL infections are limited, given the frequent coproduction of OXA-1 and TEM-1B enzymes and coresistance to antibiotic classes other than β-lactams.

尽管广谱β-内酰胺酶（ESBL）产生型肠杆菌科细菌在阿拉伯半岛已成为公共卫生问题，但关于其在儿童群体中抗菌耐药决定因素分子特性的数据却十分有限。研究目的：旨在确定卡塔尔儿童群体中产生ESBL的大肠杆菌和肺炎克雷伯菌的分子特性。研究方法：对2018年1月至12月期间在多哈Sidra Medicine从儿科患者的筛选和临床标本中分离出的产生ESBL的大肠杆菌和肺炎克雷伯菌进行了全基因组测序。研究结果：共测序327个产生ESBL的菌株：254个大肠杆菌和73个肺炎克雷伯菌。两种菌株对非β-内酰胺类抗生素的非耐药率分别为：庆大霉素18.1%和30.1%，阿米卡星0.8%和4.1%，环丙沙星41.3%和41.1%，复方新诺明65.8%和76.1%。最常见序列类型（STs）分别为大肠杆菌中的ST131（16.9%）、ST38和ST10（各8.2%），肺炎克雷伯菌中的ST307（9.7%）、ST45和ST268（各6.9%）。除一个菌株外，所有菌株均发现CTX-M型ESBL，其中CTX-M-15占87.8%。在其他β-内酰胺酶中，TEM-1B和OXA-1在41%和19.6%的菌株中被共产生。最常见的质粒介导的喹诺酮耐药基因携带者为qnr A/B/E/S（45.3%）。90%的庆大霉素非耐药菌株携带编码AAC(3)酶的基因，主要是aac(3)-IIa。在携带aac(6′)-Ib-cr的57个菌株中，只有两个对阿米卡星耐药。在96.2%的氟喹诺酮非耐药大肠杆菌和26.7%的氟喹诺酮非耐药肺炎克雷伯菌中检测到编码DNA回旋酶和拓扑异构酶IV酶的基因染色体突变。研究结论：我们的数据显示，CTX-M酶在卡塔尔儿童中广泛存在，且CTX-M-15占主导地位。鉴于OXA-1和TEM-1B酶的频繁共产生以及对抗生素类（除β-内酰胺类）的核心耐药性，治疗ESBL感染的可选碳青霉烯类药物有限。