Mapping Escherichia coli in Women with Simple Urinary Tract Infections: Phenotypic ESBL/AmpC Screening and Whole-Genome Insights from Oman

<b>Background/Objectives:</b> Simple urinary tract infections (sUTIs) are common in women and increasingly affected by multidrug-resistant (MDR) <i>Escherichia coli</i>. Extended-spectrum β-lactamase (ESBL) and AmpC producers restrict oral treatment options and promote carbapenem use. This study aimed to (i) describe the etiology and antimicrobial susceptibility of sUTIs in women of reproductive age in Oman, (ii) determine the prevalence of ESBL/AmpC-producing <i>E. coli</i>, (iii) evaluate nitroxoline, fosfomycin, mecillinam, and temocillin against ESBL and non-ESBL <i>E. coli</i>, and (iv) characterize circulating clones and resistance/virulence determinants using whole-genome sequencing (WGS). <b>Methods:</b> In this multicentric study (September 2022-August 2023), 795 uropathogens from 762 women (15-50 years) with sUTI were collected from four Omani hospitals. Identification and susceptibility testing of <i>E. coli</i> (n = 489) and <i>Klebsiella pneumoniae</i> (n = 140) using BD Phoenix and MALDI-TOF MS was performed (CLSI 2022). Thirty ESBL-producing and 82 non-ESBL <i>E. coli</i> underwent phenotypic ESBL/AmpC testing and evaluation of mecillinam, temocillin, nitroxoline, and fosfomycin. WGS was performed on 26 isolates (23 ESBL, 3 wild type) and analyzed for MLST, and SNP phylogeny using ResFinder, CARD, PlasmidFinder, VirulenceFinder. Statistical significance was set at <i>p</i> < 0.05. <b>Results:</b><i>E. coli</i> (62%) and <i>K. pneumoniae</i> (18%) were the predominant pathogens. <i>E. coli</i> showed high susceptibility to nitrofurantoin (~97%), carbapenems, aminoglycosides, and piperacillin-tazobactam, but reduced susceptibility to cephalosporins, fluoroquinolones, cotrimoxazole, and ampicillin. ESBL prevalence ranged from 38-51%; AmpC producers were rare (4.6%). Mecillinam, nitroxoline, and fosfomycin exhibited 100% activity against both ESBL and non-ESBL isolates; temocillin showed 89.3% activity in ESBL strains. WGS identified 15 sequence types dominated by ST-131, ST-1193, ST-73, and ST-174, with <i>bla</i>CTX-M-15 as the major ESBL genotype. <b>Conclusions:</b> sUTIs in Oman show a high burden of ESBL-producing <i>E. coli</i>. Nitrofurantoin, mecillinam, fosfomycin, temocillin, and nitroxoline would be effective carbapenem-sparing oral options. Continuous phenotypic and genomic surveillance are crucial to guide antimicrobial therapy and stewardship.