Genetic Predictive Factors for Nonsusceptible Phenotypes and Multidrug Resistance in Expanded-Spectrum Cephalosporin-Resistant Uropathogenic Escherichia coli from a Multicenter Cohort: Insights into the Phenotypic and Genetic Basis of Coresistance.
Nicole JacksonCheyenne R BelmontNicole J TarltonYuan Hu AllegrettiSheila Adams-SapperYolanda Yue HuangClarissa A BorgesBradley W FrazeeDanka Florence-PetrovicClarisse HufanaAnna ParkerClaire F MastrangeloShevya AwasthiIsha KaneZlatan CoralicSteve MillerJoycelyn DiazChristopher FeeCassiana E BittencourtOmai B GarnerSukantha ChandrasekaranClaudia CrandallJulian C MarchaMir H NoorbakhshPatricia Rodrigues-WongTara R deBoerLee W RileyPublished in: mSphere (2022)
Antimicrobial resistance in urinary tract infections (UTIs) is a major public health concern. This study aims to characterize the phenotypic and genetic basis of multidrug resistance (MDR) among expanded-spectrum cephalosporin-resistant (ESCR) uropathogenic Escherichia coli (UPEC) causing UTIs in California patient populations. Between February and October 2019, 577 ESCR UPEC isolates were collected from patients at 6 clinical laboratory sites across California. Lineage and antibiotic resistance genes were determined by analysis of whole-genome sequence data. The lineages ST131, ST1193, ST648, and ST69 were predominant, representing 46%, 5.5%, 4.5%, and 4.5% of the collection, respectively. Overall, 527 (91%) isolates had an expanded-spectrum β-lactamase (ESBL) phenotype, with bla CTX-M-15 , bla CTX-M-27 , bla CTX-M-55 , and bla CTX-M-14 being the most prevalent ESBL genes. In the 50 non-ESBL phenotype isolates, 40 (62%) contained bla CMY-2 , which was the predominant plasmid-mediated AmpC (pAmpC) gene. Narrow-spectrum β-lactamases, bla TEM-1B and bla OXA-1 , were also found in 44.9% and 32.1% of isolates, respectively. Among ESCR UPEC isolates, isolates with an ESBL phenotype had a 1.7-times-greater likelihood of being MDR than non-ESBL phenotype isolates ( P < 0.001). The cooccurrence of bla CTX-M-15 , bla OXA-1 , and aac(6 ' )-Ib-cr within ESCR UPEC isolates was strongly correlated. Cooccurrence of bla CTX-M-15 , bla OXA-1 , and aac(6 ' )-Ib-cr was associated with an increased risk of nonsusceptibility to piperacillin-tazobactam, cefepime, fluoroquinolones, and amikacin as well as MDR. Multivariate regression revealed the presence of bla CTX-M-55 , bla TEM-1B , and the ST131 genotype as predictors of MDR. IMPORTANCE The rising incidence of resistance to expanded-spectrum cephalosporins among Escherichia coli strains, the most common cause of UTIs, is threatening our ability to successfully empirically treat these infections. ESCR E. coli strains are often MDR; therefore, UTI caused by these organisms often leads to treatment failure, increased length of hospital stay, and severe complications (D. G. Mark, Y.-Y. Hung, Z. Salim, N. J. Tarlton, et al., Ann Emerg Med 78:357-369, 2021, https://doi.org/10.1016/j.annemergmed.2021.01.003). Here, we performed an in-depth analysis of genetic factors of ESCR E. coli associated with coresistance and MDR. Such knowledge is critical to advance UTI diagnosis, treatment, and antibiotic stewardship.
Keyphrases
- klebsiella pneumoniae
- escherichia coli
- multidrug resistant
- gram negative
- genetic diversity
- drug resistant
- genome wide
- public health
- acinetobacter baumannii
- biofilm formation
- urinary tract infection
- healthcare
- copy number
- antimicrobial resistance
- antibiotic resistance genes
- machine learning
- risk factors
- emergency department
- big data
- case report
- smoking cessation
- cross sectional
- drug induced
- replacement therapy
- data analysis
- water quality
- genome wide identification