David M Livermore1,2, Michaela Day1, Paul Cleary3, Katie L Hopkins1, Mark A Toleman4, David W Wareham5, Camilla Wiuff6, Michel Doumith1, Neil Woodford1. 1. Antimicrobial Resistance and Healthcare-Associated Infections Reference Unit, PHE National Infection Service, London, UK. 2. Norwich Medical School, University of East Anglia, Norwich, UK. 3. PHE Field Service, Liverpool, UK. 4. Cardiff University, Heath Park Campus, Cardiff, UK. 5. Blizard Institute, Queen Mary University of London, London, UK. 6. Health Protection Scotland, Glasgow, UK.
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.
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 BSACagar 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.
Authors: William C Shropshire; Samuel L Aitken; Reed Pifer; Jiwoong Kim; Micah M Bhatti; Xiqi Li; Awdhesh Kalia; Jessica Galloway-Peña; Pranoti Sahasrabhojane; Cesar A Arias; David E Greenberg; Blake M Hanson; Samuel A Shelburne Journal: J Antimicrob Chemother Date: 2021-01-19 Impact factor: 5.790
Authors: Kamrul Islam; Fekade B Sime; Steven C Wallis; Michelle J Bauer; Saiyuri Naicker; Hayoung Won; Hosam M Zowawi; Md Abu Choudhury; Tahmina Shirin; Zakir H Habib; Patrick N A Harris; Meerjady S Flora; Jason A Roberts Journal: Antimicrob Agents Chemother Date: 2022-08-04 Impact factor: 5.938
Authors: Tam T Tran; Andrew Scott; Yuan-Ching Tien; Roger Murray; Patrick Boerlin; David L Pearl; Kira Liu; James Robertson; John H E Nash; Edward Topp Journal: Appl Environ Microbiol Date: 2021-06-25 Impact factor: 4.792