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Mollenkopf dissertation.9-22-2017.13.pdf (1.6 MB)

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Epidemiology of ß-lactamase-producing Enterobacteriaceae in Humans and Livestock

Mollenkopf, Dixie Francis
http://rave.ohiolink.edu/etdc/view?acc_num=osu1505147339870873

Abstract Details

2017, Doctor of Philosophy, Ohio State University, Comparative and Veterinary Medicine.
Carbapenems have the broadest spectrum of the large ß-lactam antimicrobials and have been reserved as a “drug of last resort” against invasive Gram-positive and Gram-negative human infections. The increasing prevalence of complicated MDR infections involving extended spectrum (ESßL) and AmpC ß-lactamases has triggered the increasing need for carbapenem use. The emergence of carbapenemase-producing Enterobactericeae was described as “the end of the antibiotic era” as these potential pathogens harbor highly-mobile genetic elements that confer resistance to our most critically important drugs. In the US, nontyphoidal Salmonella are a common foodborne zoonotic pathogen causing gastroenteritis. MDR invasive Salmonella infections mediated by ESßL or AmpC genotypes are more likely to require carbapenem therapy compared to susceptible infections. Of 571 isolates, we characterized 44 blaCMY-2-bearing Salmonella that resulted from 5,050 individual cattle fecal samples from 68 large (1,000+ head capacity) US feedlots participating in the NAHMS Beef Feedlot 2011 study, and assessed risk factors for blaCMY-2 carriage. Cultured without antimicrobial selection, the isolates represented eight serotypes and carried the blaCMY-2/IncA/C gene/plasmid combination with most expressing the penta-resistance (ACSSuT) phenotype. Cattle fed chlortetracycline in their diet and heavier weight cattle were less likely to carry Salmonella with blaCMY-2. In contrast, cattle fed the macrolide feed additive tylosin and cattle in pens with increasing numbers of dairy cattle were more likely to harbor blaCMY-bearing Salmonella. To determine the prevalence of foodborne resistance mechanisms, we screened human diarrheic stool samples submitted for Clostridium difficle culture from patients of The Ohio State University Wexner Medical Center (OSUWMC) to estimate the frequency of carriage of ESßL- and AmpC- as well as carbapenemase-producing enteric bacteria. The 692 deidentified samples received between July and December 2013 were cultured using selective media to detect the resistant phenotypes. Our selective culture yielded 184 isolates (26.6 %) with reduced susceptibility to cefotaxime. Of these, 46 (6.7%) samples harbored commensal isolates carrying the AmpC blaCMY. Another 21 (3.0%) samples produced isolates harboring the ESBL blaCTX-M: 19 carrying CTX-M-15 and 2 with CTX-M-27. Additionally, 13 samples (1.9 %) produced Enterobacteriaceae or Pseudomonas spp. resistant to carbapenems. Of these, whole genome sequencing identified a prominent CRE strain, sequence type ST258, K. pneumoniae harboring blaKPC-3 and a second K. pneumoniae carrying blaNDM-1 ST1602 which had not been previously reported. Reporting the first mobile carbapenemase, blaIMP-64 on an IncQ1 plasmid, in US livestock, we followed a cohort of 350+ pigs from late sow gestation to the final finishing phase in order to better understand the maintenance of this rare resistance genotype in a large farrow-to-finish swine operation. Environmental and fecal samples were collected during 8 visits over 5 months in 2016 and screened for CPE using selective media. The frequency of IMP-64-positive environmental (n=32), sow fecal (n=30), and piglet fecal swab (120) samples was highest for all groups when the market pig cohort was between 1 and 10 d, with observed prevalence of 97%, 28%, and 18%, respectively. After weaning, blaIMP-64 was detected in a single environmental sample from a nursery pen, with no CPE recovered in the finishing phase.
Thomas Wittum (Advisor)
Joshua Daniels (Committee Member)
Gregory Habing (Committee Member)
Armando Hoet (Committee Member)
132 p.
Epidemiology
Antimicrobial resistance, Enterobacteriaceae, Carbapenemase

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Citations

  • Mollenkopf, D. F. (2017). Epidemiology of ß-lactamase-producing Enterobacteriaceae in Humans and Livestock [Doctoral dissertation, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1505147339870873

    APA Style (7th edition)

  • Mollenkopf, Dixie. Epidemiology of ß-lactamase-producing Enterobacteriaceae in Humans and Livestock. 2017. Ohio State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1505147339870873.

    MLA Style (8th edition)

  • Mollenkopf, Dixie. "Epidemiology of ß-lactamase-producing Enterobacteriaceae in Humans and Livestock." Doctoral dissertation, Ohio State University, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=osu1505147339870873

    Chicago Manual of Style (17th edition)

osu1505147339870873
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© 2017, some rights reserved.Creative Commons License Epidemiology of ß-lactamase-producing Enterobacteriaceae in Humans and Livestock by Dixie Francis Mollenkopf is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License. Based on a work at etd.ohiolink.edu.
This open access ETD is published by The Ohio State University and OhioLINK.