Table_1_Molecular Characterization of Extended-Spectrum β-Lactamase–Producing Escherichia coli and Klebsiella pneumoniae Among the Pediatric Population in Qatar.XLSX

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）产生性肠杆菌科在阿拉伯半岛构成了公共卫生问题，然而关于其儿童人群中抗菌药物耐药决定因子的分子特性的数据却相当有限。目的：本研究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。方法：对2018年1月至12月在多哈Sidra Medicine从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全基因组测序。结果：共对327个产生ESBL的菌株进行了测序：254株大肠杆菌和73株肺炎克雷伯菌。两种菌株对非β-内酰胺类抗生素的非敏感性率分别为：链霉素18.1%和30.1%，阿米卡星0.8%和4.1%，环丙沙星41.3%和41.1%，以及复方新诺明65.8%和76.1%。最常见的序列类型（STs）在大肠杆菌中为ST131（16.9%）、ST38和ST10（各占8.2%），在肺炎克雷伯菌中为ST307（9.7%）、ST45和ST268（各占6.9%）。除一株外，所有分离株均检测到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%的分离株中共同产生。最常见的质粒介导的喹诺酮耐药基因是qnr A/B/E/S（45.3%）。90%的链霉素非敏感性分离株携带编码AAC(3)酶的基因，主要是aac(3)-IIa。只有57株携带aac(6′)-Ib-cr基因的分离株中的两株对阿米卡星不敏感。在96.2%的非氟喹诺酮敏感性大肠杆菌和26.7%的非氟喹诺酮敏感性肺炎克雷伯菌中检测到编码DNA旋转酶和拓扑异构酶IV酶的基因的染色体突变。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占据主导地位。鉴于OXA-1和TEM-1B酶的频繁共产生以及对除β-内酰胺类抗生素以外的抗生素类别的交叉耐药性，治疗ESBL感染的碳青霉烯类保存选项有限。