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High rates of intestinal colonisation with fluoroquinolone-resistant ESBL-harbouring Enterobacteriaceae in hospitalised patients with antibiotic-associated diarrhoea

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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.

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Funding and role of the funding source

This work, JV and MG are supported by funding from the European Community (MOSAR network contract LSHP-CT-2007-037941; SATURN network contract FP7-HEALTH-2009-SINGLE STAGE-N°241796). The sponsor had no role in the study design, data collection, data analysis, data interpretation or writing of the report.

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Authors and Affiliations

  1. Department of Medical Microbiology, Vaccine & Infectious Disease Institute, University of Antwerp, Antwerp, Belgium

    J. Vervoort, M. Gazin, C. Lammens, H. Goossens & S. Malhotra-Kumar

  2. Division of Epidemiology and Laboratory for Molecular Epidemiology and Antibiotic Research, Tel Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

    M. Kazma, T. Kotlovsky & Y. Carmeli

  3. Department of Medical Microbiology, Campus Drie Eiken, University of Antwerp, S6, Universiteitsplein 1, 2610, Wilrijk, Belgium

    S. Malhotra-Kumar

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  1. J. Vervoort
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on behalf of the SATURN WP1 and MOSAR WP2 study groups

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Correspondence to S. Malhotra-Kumar.

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Vervoort, J., Gazin, M., Kazma, M. et al. High rates of intestinal colonisation with fluoroquinolone-resistant ESBL-harbouring Enterobacteriaceae in hospitalised patients with antibiotic-associated diarrhoea. Eur J Clin Microbiol Infect Dis 33, 2215–2221 (2014). https://doi.org/10.1007/s10096-014-2193-9

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