OXA-1 β-lactamase and non-susceptibility to penicillin/β-lactamase inhibitor combinations among ESBL-producing Escherichia coli

• Published in: Journal of antimicrobial chemotherapy Vol. 74; no. 2; pp. 326 - 333
• Main Authors: Livermore, David M, Day, Michaela, Cleary, Paul, Hopkins, Katie L, Toleman, Mark A, Wareham, David W, Wiuff, Camilla, Doumith, Michel, Woodford, Neil
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 01.02.2019
• Subjects: Anti-Bacterial Agents - pharmacology; Bacteremia - microbiology; beta-Lactamase Inhibitors - pharmacology; beta-Lactamases - genetics; Escherichia coli - drug effects; Escherichia coli - enzymology; Escherichia coli - genetics; Escherichia coli Infections - microbiology; Genome, Bacterial; Humans; Microbial Sensitivity Tests; Penicillins - pharmacology; Plasmids; United Kingdom; Whole Genome Sequencing; United Kingdom
• ISSN: 0305-7453; 1460-2091
• DOI: 10.1093/jac/dky453

Abstract Background ESBL-producing Escherichia coli have expanded globally since the turn of the century and present a major public health issue. Their in vitro susceptibility to penicillin/inhibitor combinations is variable, and clinical use of these combinations against ESBL producers remains controversial. We hypothesized that this variability related to co-production of OXA-1 penicillinase. Methods During a national study we collected 293 ESBL-producing E. coli from bacteraemias, determined MICs by BSAC agar dilution, and undertook genomic sequencing with Illumina methodology. Results The collection was dominated by ST131 (n = 188 isolates, 64.2%) and blaCTX-M-15 (present in 229 isolates, 78.2%); over half the isolates (159/293, 54.3%) were ST131 with blaCTX-M-15. blaOXA-1 was found in 149 ESBL producers (50.9%) and blaTEM-1/191 in 137 (46.8%). Irrespective of whether all isolates were considered, or ST131 alone, there were strong associations (P < 0.001) between co-carriage of blaOXA-1 and reduced susceptibility to penicillin/inhibitor combinations, whereas there was no significant association with co-carriage of blaTEM-1/191. For piperacillin/tazobactam the modal MIC rose from 2 mg/L in the absence of blaOXA-1 to 8 or 16 mg/L in its presence; for co-amoxiclav the shift was smaller, from 4 or 8 to 16 mg/L, but crossed the breakpoint. blaOXA-1 was strongly associated with co-carriage also of aac(6′)-Ib-cr, which compromises amikacin and tobramycin. Conclusions Co-carriage of OXA-1, a penicillinase with weak affinity for inhibitors, is a major correlate of resistance to piperacillin/tazobactam and co-amoxiclav in E. coli and is commonly associated with co-carriage of aac(6′)-Ib-cr, which narrows aminoglycoside options.