Inherent colistin resistance in Genogroups of the Enterobacter cloacae complex: epidemiological, genetic and biochemical analysis from the BSAC Resistance Surveillance Programme

Shazad Mushtaq, Rosy Reynolds, Michael C. Gilmore, Olubukola Eshu, Inma Garcia-Romero, Aiysha Chaudhry, Carolyne Horner, Toby L. Bartholomew, Miguel A. Valvano, Magdalena Dry, John Murray, Bruno Pichon, David M. Livermore on behalf of the BSAC Resistance Surveillance Committe

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Abstract

Background: Polymyxins have re-entered use against problem Gram-negative bacteria. Resistance rates are uncertain, with estimates confounded by selective testing. Methods: The BSAC Resistance Surveillance Programme has routinely tested colistin since 2010; we reviewed data up to 2017 for relevant Enterobacterales (n=10,914). Unexpectedly frequent resistance was seen among the Enterobacter cloacae complex isolates (n=1749); for these, we investigated relationships to species, genome, carbon source utilisation and LPS structure. Results: Annual colistin resistance rates among E. cloacae complex isolates were 4.4% to 20%, with a rising trend among bloodstream organisms; in contrast, annual rates for Escherichia coli, Klebsiella spp. and E. aerogenes generally remained <2%. WGS split the E. cloacae complex isolates into 7 Genogroup clusters, designated A-G. Among isolates assigned to Genogroups A-D, 47/50 sequenced were colistin resistant, and many, from Genogroups A-C identified as E. asburiae. Isolates belonging to Genogroups E-G consistently identified as E. cloacae and were rarely (only 3/45 representatives sequenced) were colistin resistant. Genogroups F and G – the predominant colistin-susceptible clusters – were metabolically distinct from other clusters, notably regarding utilisation or not of L-fucose, formic acid, D-serine, adonitol, myo-inositol, L-lyxose and polysorbates. LPS from resistant organisms grown without colistin pressure lacked substitutions with 4-amino-arabinose or ethanolamine but was more structurally complex, with more molecular species present. Conclusions: Colistin resistance is frequent in E. cloacae the complex and increasing among bloodstream isolates. It is associated with: (i) particular genomic and metabolic clusters, (ii) identification as E. asburiae and (iii) with more complex LPS architectures.
Original languageEnglish
JournalJournal of Antimicrobial Chemotherapy
Early online date08 Jun 2020
Publication statusEarly online date - 08 Jun 2020

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