Evaluation of activity of ceftolozane/tazobactam and comparators against recent clinical bacterial isolates, and genomics of and isolates that demonstrated resistance to ceftolozane/tazobactam: data from Kuwait and Oman.

BACKGROUND

The treatment options for infections caused by MDR Gram-negative bacteria have been limited, especially for infections caused by bacteria that produce carbapenemases and/or ESBLs. Ceftolozane/tazobactam is a cephalosporin/β-lactamase inhibitor developed to treat Gram-negative bacteria.

METHODS

Ceftolozane/tazobactam and 14 comparators (amikacin, aztreonam, cefepime, cefotaxime, cefoxitin, ceftazidime, ceftriaxone, ciprofloxacin, colistin, ertapenem, imipenem, levofloxacin, meropenem and piperacillin/tazobactam) were evaluated against and Enterobacterales isolates collected from Kuwait and Oman (= 606) during 2016-17. In addition, further analysis of resistance mechanisms to ceftolozane/tazobactam was done utilizing WGS. Non-susceptible isolates from ceftolozane/tazobactam surveillance were selected for analysis. Overall, 35 strains underwent WGS.

RESULTS

Among isolates from Kuwait, susceptibility of , and to ceftolozane/tazobactam was 79.8%, 95.7% and 87.5%, respectively, and from Oman was 92.3%, 93.1% and 88.5%, respectively. No with a ceftolozane/tazobactam MIC <32 mg/L encoded β-lactamases besides normal chromosomal enzymes (PDC variants or OXA-50-like) whereas all but one isolate with MIC >32 mg/L encoded either MBLs (60%), VEB-1 (19%) or additional OXAs (3.7%).

CONCLUSIONS

Colistin followed by ceftolozane/tazobactam showed the greatest activity against . Enterobacterales showed more susceptibility to ceftolozane/tazobactam than to piperacillin/tazobactam, but meropenem and colistin showed better activity.