Molecular Characterization of Extended-Spectrum β-Lactamase-Producing Escherichia coli and Klebsiella pneumoniae Among the Pediatric Population in Qatar.
Introduction
Although 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.


Aim
To determine the molecular characteristics of ESBL-producing Escherichia coli and Klebsiella pneumoniae in the pediatric population of Qatar.


Methods
Whole-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.


Results
A 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.


Conclusion
Our 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.
['Perez-Lopez|Andres|A|', 'Sundararaju|Sathyavathi|S|', 'Al-Mana|Hassan|H|', 'Tsui|Kin Ming|KM|', 'Hasan|Mohammad Rubayet|MR|', 'Suleiman|Mohammed|M|', 'Janahi|Mohammed|M|', 'Al Maslamani|Eman|E|', 'Tang|Patrick|P|']
extended-spectrum β-lactamases children whole-genome sequencing E. coli K. pneumoniae CTX-M-15 fluoroquinolones