title: High rates of intestinal colonisation with fluoroquinolone-resistant ESBL-harbouring Enterobacteriaceae in hospitalised patients with antibiotic-associated diarrhoea.
abstract: The purposes of this study were to investigate the intestinal carriage of extended-spectrum β-lactamase-harbouring Enterobacteriaceae (ESBL-EN) and associated fluoroquinolone resistance (FQ-R) in 120 hospitalised patients with antibiotic-associated diarrhoea, and to investigate a correlation between Clostridium difficile (C. difficile) infection and intestinal colonisation with ESBL-EN in these patients. Stool samples were screened for C. difficile infection by toxin A/B enzyme-linked immunosorbent assay (ELISA) and for the presence of enterobacterial isolates producing β-lactamases by plating on β-lactamase screening (BLSE) agar. Recovered isolates were confirmed pheno- and genotypically for the presence of ESBL genes (bla CTX-M, bla TEM, bla SHV) by the double-disc synergy test and polymerase chain reaction (PCR) sequencing, and tested for the presence of topoisomerase mutations (gyrA, parC) and plasmid-mediated quinolone resistance (PMQR) determinants [qnrA, qnrB, qnrS, qepA, aac(6')-Ib-cr] by PCR sequencing. ESBL-EN were detected in 44/120 (37 %) stool samples. C. difficile-infected patients showed a significantly higher frequency of intestinal colonisation with ESBL-EN compared to C. difficile non-infected patients (62 % vs. 31 %, p = 0.008). Of the 73 ESBL-EN recovered, 46 (63 %) showed high-level FQ-R [ciprofloxacin minimum inhibitory concentration (MIC) ≥32 mg/L]. The largest group consisted of 21 bla CTX-M-15-harbouring Enterobacteriaceae (ciprofloxacin MIC ≥64 mg/L) with multiple topoisomerase mutations in gyrA and parC, in combination with co-carriage of aac(6')-Ib-cr. Most of them were Escherichia coli isolates belonging to sequence types ST131 and ST410. We found remarkably high rates of intestinal colonisation with high-level FQ-R ESBL-EN in hospitalised patients with antibiotic-associated diarrhoea, especially among C. difficile-infected patients. These data underscore the need for stringent infection control to contain this potentially infectious and multidrug-resistant reservoir.
authors.affiliation: Department of Medical Microbiology, Vaccine & Infectious Disease Institute, University of Antwerp, Antwerp, Belgium.
authors.forename: J
authors.initials: J
authors.lastname: Vervoort
authors.forename: M
authors.initials: M
authors.lastname: Gazin
authors.forename: M
authors.initials: M
authors.lastname: Kazma
authors.forename: T
authors.initials: T
authors.lastname: Kotlovsky
authors.forename: C
authors.initials: C
authors.lastname: Lammens
authors.forename: Y
authors.initials: Y
authors.lastname: Carmeli
authors.forename: H
authors.initials: H
authors.lastname: Goossens
authors.forename: S
authors.initials: S
authors.lastname: Malhotra-Kumar
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D016360:Clostridioides difficile / Q000254:growth & development / Q000302:isolation & purification; D015331:Cohort Studies; D003967:Diarrhea / Q000382:microbiology*; D004755:Enterobacteriaceae / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics / Q000254:growth & development*; D004756:Enterobacteriaceae Infections / Q000139:chemically induced / Q000382:microbiology*; D004761:Enterocolitis, Pseudomembranous / Q000382:microbiology; D005243:Feces / Q000382:microbiology; D024841:Fluoroquinolones / Q000494:pharmacology*; D006801:Humans; D007422:Intestines / Q000382:microbiology*; D001618:beta-Lactamases / Q000096:biosynthesis
chemical_list: D000900:Anti-Bacterial Agents; D024841:Fluoroquinolones; D001618:beta-Lactamases