Association of Virulence Markers With Resistance to Oral Antibiotics in Escherichia coli Isolates Causing Uncomplicated Community-Acquired Cystitis.

Abstract

UropathogenicEscherichia coli(UPEC) strains equipped with putative virulence factors (VFs) are known to cause approximately 90% of lower urinary tract infections (UTIs) or cystitis affecting individuals of all age groups. Only limited laboratory-based data on the correlation of antimicrobial resistant patterns and VFs of UPEC are available. A total of 100 non-duplicate E. coli isolates associated with community-acquired UTIs in sexually active women were analysed for antimicrobial susceptibility patterns and putative virulence-associated genes. Antimicrobial susceptibility testing (AST) was carried out by the Kirby-Bauer disk diffusion method, and results were interpreted as per Clinical and Laboratory Standards Institute (CLSI) guidelines. The isolates non-susceptible to ≥1 agent in ≥3 different antimicrobial categories were considered multidrug-resistant (MDR). Multiplex polymerase chain reaction assay was performed on each E. coli isolateto characterize putative virulence genes (VGs) such as papA, malX, PAI, ibeA, fimH, fyuA, sfa/focDE, papGIII, iutA, papGI, kpsMTII, hlyA, papGII, traT, afa/draBC, cnf1, vat, and yfcV. Results: Capsule synthesis gene kpsMTII (59%)was the most predominant VG present, followed by serum resistance-associated transfer protein gene traT (58%) and adhesin gene fimH (57%); however, adhesin gene papGI (2%) was the least present. The prevalence of antimicrobial resistance was relatively high for commonly used oral antimicrobials of UTItreatment, such as trimethoprim-sulfamethoxazole (68%) and fluoroquinolones (63%). The majority of isolates were MDR (78%) and resistant to extended-spectrum cephalosporins (63.5%). Isolates resistant to norfloxacin and trimethoprim-sulfamethoxazole were also resistant to almost all available oral antimicrobials. Isolates resistant to extended-spectrum cephalosporins showed increased resistance to aztreonam and trimethoprim-sulfamethoxazole (84.6% each)and fluoroquinolones (ciprofloxacin and norfloxacin; 81.5% each). Fosfomycin and nitrofurantoin were the most sensitive antimicrobials for all these resistant isolates. In a multivariate analysis, it was found that MDR isolates were associated with many of the VGs; fimH (65.4%) being the most frequent followed by traT (64.1%). traT (66.2%) and iutA (60.3%) were most commonly present in E. coli isolates resistant to trimethoprim-sulfamethoxazole, while66.7% norfloxacin-resistant isolates have them.Isolates resistant to extended-spectrum cephalosporins were most commonly associated with fimH and traT (66.2% each). However, E. coli isolates positive for sfa/focDE and vat were more sensitive to norfloxacin and trimethoprim-sulfamethoxazole and were non-MDR strains predominantly (p < 0.05). Only two VGs (fimH and traT)were significantly associated with MDR strains. The results of the present study clearly show the association of VFs with some of the commonly used oral antibiotics emphasizing the need for further molecular studies and surveillance programs to monitor drug-resistant UPEC so as to form optimized diagnostic stewardship and appropriate regimen for patient treatment. The reason behind this phenomenon of association has not been studied in much detail herebut it can be assumed that genes responsible for drug resistance may share neighbouring loci with VGs on the mobile genetic elements (e.g., plasmid), which transfer together from one bacterium to another.