Activity of ceftolozane/tazobactam and comparators against gram-negative bacilli: Results from the Study for Monitoring Antimicrobial Resistance Trends (SMART - Brazil), 2018-2021

Increased spread of antimicrobial resistance by Gram-Negative Bacilli (GNB) poses a global challenge, with exacerbated burden post-pandemic. The aim of this study was to investigate the in vitro activity of ceftolozane/ tazobactam and its comparators against the frequently identified GNB isolated from patients admitted to Brazilian medical sites between the year 2018-2019 and 2020-2021. The impact of pandemic on antimicrobial resistance and presence of (3-lactamase genes were also evaluated. Antimicrobial susceptibility testing and molecular characterization of ss-lactamase encoding genes using Polymerase Chain Reaction (PCR) and DNA sequencing were carried out from GNB isolated mostly from intra-abdominal, respiratory, and urinary tract infections and interpreted following BrCAST/EUCAST guidelines. A total of 3994 GNB isolates were evaluated which mostly included E. coli, K. pneumoniae and P. aeruginosa. Ceftolozane/tazobactam remained highly active against E. coli isolates during both 2018-2019 (96.0 %) and 2020-2021 (98.5 %). Among K. pneumoniae, ceftolozane/tazobactam (47.6 % and 43.0 % susceptible during 2018-2019 and 2020-2021, respectively) showed poor activity due to blaKPC-2. Colistin and ceftolozane/tazobactam were the most active (3-lactam agents tested against P. aeruginosa in 2018-2019 (99.3 % and 88.8 %) and 2020-2021 (100 % and 92.8 %), including ceftazidime and meropenem resistant isolates. (3-lactamase encoding gene characterization was carried out and both carbapenemases and Extended-Spectrum (3-Lactamase (ESBL) producers were found in E. coli, K. pneumoniae and P. aeruginosa isolates. Ceftolozane/tazobactam documented remarkable in vitro activity against E. coli and P. aeruginosa isolates in Brazil, both pre- and post-pandemic periods and could constitute an effective therapeutic option for the treatment of urinary tract infections, intra-abdominal infections, and respiratory tract infections.