Tazobactam/ceftolozane (TAZ/CTLZ) and relebactam/imipenem (REL/IPM) susceptibility in Japan: Nationwide surveillance of respiratory bacterial pathogens in 2019/20.

Tazobactam/ceftolozane (TAZ/CTLZ) and relebactam/imipenem/cilastatin (REL/IPM/CS) are expected to be effective for treating patients with antimicrobial-resistant infections, particularly gram-negative pathogens, but nationwide surveillance of these has not been investigated thoroughly in Japan. Pseudomonas aeruginosa (n = 164), Klebsiella pneumoniae (n = 141), and Haemophilus influenzae (n = 156) isolated from respiratory infected patients in Japan from June 2019 through December 2020 provided by the Japanese Surveillance Committee were used. Antimicrobial susceptibility testing for TAZ/CTLZ, REL/IPM and comparator agents against isolates were carried out by broth microdilution methods according to the Clinical and Laboratory Standards Institute standard. The MIC50/90 of TAZ/CTLZ against P. aeruginosa and K. pneumoniae were 0.5/1 μg/mL and 0.25/0.5 μg/mL, those of REL/IPM were 0.25/1 μg/mL and 0.25/0.5 μg/mL, respectively, and all isolates were susceptible to both drugs. Susceptible rates for P. aeruginosa to IPM, ceftazidime (CAZ), and levofloxacin (LVFX) were 84.1, 87.8, and 76.8 %, and those of K. pneumoniae to tazobactam/piperacillin, CAZ, and LVFX were 98.6, 98.6, and 95.0 %, respectively. The MIC50/90 of TAZ/CTLZ for H. influenzae were 0.5/2 μg/mL, comparable to those of cefepime (CFPM), 1/2 μg/mL, but susceptible rate to TAZ/CTLZ and CFPM differed at 50.6 and 100 %, respectively. This difference was estimated from the different clinical breakpoints between TAZ/CTLZ (0.5 μg/mL) and CFPM (2 μg/mL) and the epidemiological prevalence of β-lactamase negative ampicillin resistance (BLNAR), which is high in Japan but rare in the US/EU. Excellent in vitro activities for TAZ/CTLZ and REL/IPM against major causative gram-negative bacteria in RTI patients were observed.