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

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 bacteraem as, determined MICs by BSAC agar dilution, and undertook genomic sequencing with Illumina methodology. Results: The collection was dominated by ST131 = 188 isolates, 64,2%) and bla(CTX-M-15) (present in 229 isolates, 78,2%); over half the isolates (159/293, 54.3%) were ST131 with bla(CTX-M-15). bla(OXA-1) was found in 149 ESBL producers (50.9%) and bla(TEM-1/191)1 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 bla(OXA-1) and reduced susceptibility to penicillin/inhibitor combinations, whereas there was no significant association with co-carriage of bla(TEM-1/191), For piperacillin/tazobactam the modal MIC rose from 2 mg/L in the absence of bla(OXA-1) to 8 or 16 mg/L in its presence; for co-amoxiclay the shift was smaller, from 4 or 8 to 16 mg/L, but crossed the breakpoint. bla(OXA-1), was strongly associated with co-carriage also of aac(69-1b-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 piperacillinhazobactam and co-amoxiclay in E. coil and is commonly associated with co-carriage of aac(6')-Ib-cr, which narrows aminoglycoside options.