Activity of ceftolozane/tazobactam against Gram-negative isolates among different infections in Hong Kong: SMART 2017-2019

Introduction. Ceftolozane/tazobactam was approved by the Drug Office. Department of Health, Government of the Hong Kong Special Administrative Region in 2017. Hypothesis/Gap Statement. Currently the in vitro activity of ceftolozane/tazobactam against Gram-negative pathogens isolated from patients in Hong Kong is undocumented. It would be prudent to document the activity of ceftolozane/tazobactam against Pseudomonas aeruginosa and Enterobacterales isolated from hospitalized patients in Hong Kong. Aim. To describe the in vitro susceptibility of recent clinical isolates of P aeruginosa and the two most common Enterobacterales species (Klebsiella pneumoniae, Escherichia coil) cultured from respiratory tract, intra-abdominal, urinary tract and bloodstream infection samples to ceftolozane/tazobactam and other commonly used antimicrobial agents. Methodology. CLSI-defined broth microdilution MICs were determined and interpreted for Gram-negative isolates collected in Hong Kong from 2017 to 2019 by the SMART surveillance programme. Results. For P aeruginosa, 96.7% of isolates (n=210) were susceptible to ceftolozane/tazobactam, while susceptibility rates were >= 14% lower to meropenem (82.9% susceptible). cefepime (82.4%), ceftazidime (81.4%), piperacillin/tazobactam (76.7%) and levofloxacin (79.5%). Ceftolozane/tazobactam inhibited 85.7% of piperacillin/tazobactam-nonsusceptible isolates. 80.6-82.1% of cefepime-. ceftazidime- or meropenem-nonsusceptible isolates, and 75.9% of multidrug-resistant (MDR) isolates of P aeruginosa. For K. pneumoniae, 96.1% of isolates (n=308) were susceptible to ceftolozane/tazobactam compared with meropenem (99.0% susceptible), piperacillin/tazobactam (93.8%), cefepime (85.7%) and ceftazidime (85.4%). The majority (88.3%) of ESBL (extended-spectrum beta-lactamase) non-CRE (carbapenem-resistant Enterobacterales) phenotype isolates of K. pneumoniae were susceptible to ceftolozane/tazobactam, comparable to piperacillin/tazobactam (85.0%) but lower than meropenem (100%). For E. coli, 98.5% of isolates (n=609) were susceptible to ceftolozane/tazobactam compared to meropenem (99.3% susceptible), piperacillin/tazobactam (96.7%). ceftazidime (82.3%) and cefepime (76.5%). The majority (96.7%) of ESBL non-CRE phenotype isolates of E. coli were susceptible to ceftolozane/tazobactam, similar to both meropenem (100%) and piperacillin/tazobactam (94.5%). Conclusions. Overall, >96% of clinical isolates of P. aeruginosa, K. pneumoniae and E. coli collected in Hong Kong in 2017-2019 were susceptible to ceftolozane/tazobactam, while the activity of several commonly prescribed beta-lactams was reduced, especially for P aeruginosa. Continued surveillance of ceftolozane/tazobactam and other agents is warranted.