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 Jackson; Cheyenne R. Belmont; Nicole J. Tarlton; Yuan Hu Allegretti; Sheila Adams-Sapper; Yolanda Yue Huang; Clarissa A. Borges; Bradley W. Frazee; Danka Florence-Petrovic; Clarisse Hufana; Anna Parker; Claire F. Mastrangelo; Shevya Awasthi; Isha Kane; Zlatan Coralic; Steve Miller; Joycelyn Diaz; Christopher Fee; Cassiana E. Bittencourt; Omai Garner; Sukantha Chandrasekaran; Claudia Crandall; Julian C. Marcha; Mir H. Noorbakhsh; Patricia Rodrigues-Wong; Tara R. deBoer; Lee W. Riley

doi:10.1128/msphere.00471-22

mSphere (Dec 2022)

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 Jackson,
Cheyenne R. Belmont,
Nicole J. Tarlton,
Yuan Hu Allegretti,
Sheila Adams-Sapper,
Yolanda Yue Huang,
Clarissa A. Borges,
Bradley W. Frazee,
Danka Florence-Petrovic,
Clarisse Hufana,
Anna Parker,
Claire F. Mastrangelo,
Shevya Awasthi,
Isha Kane,
Zlatan Coralic,
Steve Miller,
Joycelyn Diaz,
Christopher Fee,
Cassiana E. Bittencourt,
Omai Garner,
Sukantha Chandrasekaran,
Claudia Crandall,
Julian C. Marcha,
Mir H. Noorbakhsh,
Patricia Rodrigues-Wong,
Tara R. deBoer,
Lee W. Riley

Affiliations

Nicole Jackson: School of Public Health, Division of Infectious Diseases and Vaccinology, University of California, Berkeley, California, USA
Cheyenne R. Belmont: School of Public Health, Division of Epidemiology, University of California, Berkeley, California, USA
Nicole J. Tarlton: Department of Microbiology, BioAmp Diagnostics, Inc., San Carlos, California, USA
Yuan Hu Allegretti: School of Public Health, Division of Epidemiology, University of California, Berkeley, California, USA
Sheila Adams-Sapper: School of Public Health, Division of Infectious Diseases and Vaccinology, University of California, Berkeley, California, USA
Yolanda Yue Huang: Division of Environmental Genomics and Systems Biology, Lawrence Berkeley National Laboratory, Berkeley, California, USA
Clarissa A. Borges: School of Public Health, Division of Infectious Diseases and Vaccinology, University of California, Berkeley, California, USA
Bradley W. Frazee: Department of Emergency Medicine, Highland Hospital, Alameda Health System, Oakland, California, USA
Danka Florence-Petrovic: Department of Laboratory Medicine and Pathology, Highland Hospital, Alameda Health System, Oakland, California, USA
Clarisse Hufana: Department of Microbiology, BioAmp Diagnostics, Inc., San Carlos, California, USA
Anna Parker: School of Public Health, Division of Infectious Diseases and Vaccinology, University of California, Berkeley, California, USA
Claire F. Mastrangelo: School of Public Health, Division of Infectious Diseases and Vaccinology, University of California, Berkeley, California, USA
Shevya Awasthi: School of Public Health, Division of Infectious Diseases and Vaccinology, University of California, Berkeley, California, USA
Isha Kane: Department of Microbiology, BioAmp Diagnostics, Inc., San Carlos, California, USA
Zlatan Coralic: Department of Pharmacy, University of California, San Francisco, California, USA
Steve Miller: Department of Laboratory Medicine, University of California, San Francisco, California, USA
Joycelyn Diaz: Department of Laboratory Medicine, University of California, San Francisco, California, USA
Christopher Fee: Department of Laboratory Medicine, University of California, San Francisco, California, USA
Cassiana E. Bittencourt: Department of Pathology and Laboratory Medicine, University of California, Irvine, California, USA
Omai Garner: Department of Pathology and Laboratory Medicine, University of California, Los Angeles, California, USA
Sukantha Chandrasekaran: Department of Pathology and Laboratory Medicine, University of California, Los Angeles, California, USA
Claudia Crandall: John Muir Microbiology, John Muir Health, Concord, California, USA
Julian C. Marcha: John Muir Microbiology, John Muir Health, Concord, California, USA
Mir H. Noorbakhsh: Sutter Shared Lab, Sutter Health, Livermore, California, USA
Patricia Rodrigues-Wong: Sutter Shared Lab, Sutter Health, Livermore, California, USA
Tara R. deBoer: Department of Chemistry, BioAmp Diagnostics, Inc., San Carlos, California, USA
Lee W. Riley: School of Public Health, Division of Infectious Diseases and Vaccinology, University of California, Berkeley, California, USA

DOI: https://doi.org/10.1128/msphere.00471-22
Journal volume & issue: Vol. 7, no. 6

Abstract

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ABSTRACT 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 blaCTX-M-15, blaCTX-M-27, blaCTX-M-55, and blaCTX-M-14 being the most prevalent ESBL genes. In the 50 non-ESBL phenotype isolates, 40 (62%) contained blaCMY-2, which was the predominant plasmid-mediated AmpC (pAmpC) gene. Narrow-spectrum β-lactamases, blaTEM-1B and blaOXA-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 blaCTX-M-15, blaOXA-1, and aac(6′)-Ib-cr within ESCR UPEC isolates was strongly correlated. Cooccurrence of blaCTX-M-15, blaOXA-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 blaCTX-M-55, blaTEM-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.

Published in mSphere

ISSN: 2379-5042 (Online)
Publisher: American Society for Microbiology
Country of publisher: United States
LCC subjects: Science: Microbiology
Website: https://journals.asm.org/journal/msphere

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