Success of ceftazidime-avibactam and aztreonam in combination for a refractory biliary infection due to blaIMP-4 carbapenemase-producing Enterobacter hormaechei subsp oharae. CAZ-AVI-AZT for blaIMP-4 E.hormaechei subsp oharae

BackgroundInfections due to metallo-beta-lactamase (MBL)-producing organisms are becoming a significant problem, and antibiotic treatment options are limited. Aztreonam inhibits MBLs, and its use in combination with ceftazidime-avibactam (CAZ-AVI-AZT) to inhibit other beta-lactamases, shows promise. This combination was used successfully to treat a difficult infection.MethodsA 45-year-old woman suffered from recurrent and sustained MBL+ (blaIMP-4) Enterobacter cloacae complex bacteremia from an undrained biliary source, who had failed nine alternative antibiotic regimens over a five-month period. The tenth episode was successfully treated with CAZ-AVI-AZT, and she has had no further relapses. Three of the isolates underwent whole-genome sequencing on the MiSeq platform and were analysed with the Nullarbor pipeline.ResultsA layered Etest method for synergy between CAZ-AVI and aztreonam demonstrated an MIC of 2mg/L for the combination. Isolates were identified by WGS as Enterobacter hormaechei subsp oharae. All three of the isolates had blaTEM-4 ESBL, blaOXA-1 and blaACT-25. Two of the carbapenem-resistant isolates contained blaIMP-4 and blaOXA-368. DiscussionWhile aztreonam inhibits MBLs, MBL-positive isolates often express other beta-lactamase enzymes. Avibactam inhibits ESBLs and other beta-lactamases, and its use in this case possibly contributed to therapeutic success due to inhibition of the concomitant blaTEM-4 in the isolates. This case demonstrates that phenotypic antimicrobial susceptibility testing, including layered Etests for synergy, back up by whole-genome sequencing, is able to produce results that allow tailored antimicrobial therapy in difficult infections. This case adds to the evidence for using CAZ-AVI-AZT in serious MBL infections.