Evaluation of in Vitro Activity of Ceftazidime/Avibactam and Ceftolozane/Tazobactam against ESBL-producing Enterobacterales Isolated from Intensive Care Units from Qatar

OBJECTIVES: Extended-spectrum -lactamases (ESBLs) mechanism of resistance in Enterobacterales leads to poor clinical outcomes. Ceftazidime/avibactam and ceftolozane/tazobactam are two broad-spectrum antimicrobial combinations that are effective against multidrug-resistant organisms with regional variations. This study aims to evaluate the antimicrobial susceptibility test (AST) for both combinations against ESBL-producing Enterobacterales isolated from intensive care units (ICUs) in tertiary hospitals from November 2012 to October 2013 in Qatar. METHODS: A total of 629 Enterobacterales isolates from ICUs were screened for ESBL production using BD-Phoenix(TM) confirmed by double-disk potentiation, while ESBL-genes were detected by polymerase chain reaction. The ASTs for ceftazidime/avibactam and ceftolozane/tazobactam were assessed by minimum inhibitory concentration (MIC) test strips. A single isolate that was resistant to both combinations was subjected to whole-genome sequencing. RESULTS: The prevalence of ESBL-producing Enterobacterales isolated from ICUs was 17.3% (109/629) with predominance of Klebsiella pneumoniae (56/109; 51.4%) and Escherichia coli (38/109; 34.9%). The susceptibility of ceftazidime/avibactam and ceftolozane/tazobactam against ESBL-producers was 99.1% (108/109) and most (81/109; 74.3%) had MICs < 0.5 for both combinations. The predominant ESBL-gene was blaCTX-M (72/109; 66.1%). A single isolate that was resistant to both combinations harbored multiple ESBL resistant-genes including blaVEB-5 and blaVIM-2. CONCLUSIONS: ESBL-producing Enterobacterales isolated from ICUs were predominantly K. pneumoniae and E. coli, mainly harboring blaCTX-M gene. They were highly susceptible to ceftazidime/avibactam and ceftolozane/tazobactam suggesting potential alternatives to currently available therapeutic options.