Shazad Mushtaq1, Rosy Reynolds2,3,4, Michael C Gilmore5,6, Olubukola Esho7,8, Rachael Adkin1, Inmaculada García-Romero5, Aiysha Chaudhry1, Carolyne Horner2, Toby L Bartholomew5,9, Miguel A Valvano5, Magdalena Dry10, John Murray10,11, Bruno Pichon1, David M Livermore1,12. 1. Antimicrobial Resistance & Healthcare Associated Infection Reference Unit, Public Health England, Colindale, London. 2. British Society for Antimicrobial Chemotherapy, Birmingham, UK. 3. Department of Medical Microbiology, Southmead Hospital, Bristol, UK. 4. University of Bristol Medical School (Population Health Sciences), Canynge Hall, 39 Whatley Road, Bristol BS8 2PS, UK. 5. The Wellcome-Wolfson Institute for Experimental Medicine, Queens University, Belfast, UK. 6. Laboratory for Molecular Infection Medicine Sweden (MIMS), Department of Molecular Biology, Umeå University, Umeå, Sweden. 7. Department of Medical Microbiology, Norfolk and Norwich University Hospital, Norwich, UK. 8. Department of Clinical Microbiology and Infection Control, Royal Gwent Hospital, Cardiff Road, Newport, Gwent NP20 2UB, UK. 9. Excerpta Medica BV, 90 Southwark Street, London SE1 0SW, UK. 10. Quotient Bio Analytical Sciences and HFL Sport Science, LGC Group, Fordham, UK. 11. Fisher Scientific Ltd, Bishop Meadow Road, Loughborough LE1 5RG, UK. 12. Norwich Medical School, University of East Anglia, Norwich, UK.
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 utilization and LPS structure. RESULTS: Annual colistin resistance rates among E. cloacae complex isolates were 4.4%-20%, with a rising trend among bloodstream organisms; in contrast, annual rates for Escherichia coli and Klebsiella spp. (including K. aerogenes) generally remained <2%. WGS split the E. cloacae complex isolates into seven genogroup clusters, designated A-G. Among isolates assigned to genogroups A-D, 47/50 sequenced were colistin resistant, and many of those belonging to 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) colistin resistant. Genogroups F and G, the predominant colistin-susceptible clusters, were metabolically distinct from other clusters, notably regarding utilization 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 the E. cloacae 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.
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 utilization and LPS structure. RESULTS: Annual colistin resistance rates among E. cloacae complex isolates were 4.4%-20%, with a rising trend among bloodstream organisms; in contrast, annual rates for Escherichia coli and Klebsiella spp. (including K. aerogenes) generally remained <2%. WGS split the E. cloacae complex isolates into seven genogroup clusters, designated A-G. Among isolates assigned to genogroups A-D, 47/50 sequenced were colistin resistant, and many of those belonging to 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) colistin resistant. Genogroups F and G, the predominant colistin-susceptible clusters, were metabolically distinct from other clusters, notably regarding utilization 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 the E. cloacae 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.
Authors: Richard D Smith; Christi L McElheny; Jerilyn R Izac; Francesca M Gardner; Courtney E Chandler; David R Goodlett; Yohei Doi; J Kristie Johnson; Robert K Ernst Journal: Microbiol Spectr Date: 2022-02-02