Activity of ceftolozane-tazobactam against Gram-negative pathogens isolated from lower respiratory tract infections in the Asia-Pacific region: SMART 2015-2016

Abstract

The aim of this study was to investigate the susceptibility of respiratory Gram-negative bacteria to ceftolozane/tazobactam and other antibiotics in the Asia-Pacific region during 2015-2016. MICs were determined using the CLSI standard broth microdilution method and interpreted accordingly. Pseudomonas aeruginosa (1574 isolates), Klebsiella pneumoniae (1226), Acinetobacter baumannii (627) and Escherichia coli (476) accounted for 73.1% of 5342 Gram-negative respiratory pathogens. Susceptibility to ceftolozane/tazobactam of individual Enterobacteriaceae was >80%, except for Enterobacter cloacae (76.6%). Ceftolozane/tazobactam inhibited 81.9% of K. pneumoniae and 91.9% of E. coli, with respective MIC₅₀/MIC₉₀ values of 0.5/>32 and 0.25/2 mg/L. For carbapenem-susceptible, ESBL-producing K. pneumoniae and E. coli, susceptibility was 65.5% and 93.3%, respectively, and respective MIC₅₀/MIC₉₀ values were 2/>32 and 0.5/2 mg/L. Bla_{CTX-M-1 group} was most prevalent in selected ESBL-producing K. pneumoniae (40 of 54 isolates) and E. coli (15 of 22 isolates), with ceftolozane/tazobactam susceptibility rates of 50% and 80%, respectively. Bla_SHV-ESBL was the second most prevalent, and ceftolozane/tazobactam inhibited 20% of 20 K. pneumoniae isolates with bla_SHV-ESBL. The only effective antibiotics for carbapenem-non-susceptible K. pneumoniae (111 isolates) and E. coli (24 isolates) were amikacin and colistin. Ceftolozane/tazobactam was effective against almost all tested P. aeruginosa and carbapenem-non-susceptible strains, with susceptibility of 92.3% and 72.8%, respectively; the respective MIC₅₀/MIC₉₀ values were 1/4 and 2/>32 mg/L. The high susceptibility of ceftolozane/tazobactam remained in different age groups, patient locations, recovery times and countries, except Vietnam. In conclusion, ceftolozane/tazobactam was effective against most respiratory Gram-negative pathogens in the Asia-Pacific region; however, the emergence of carbapenem resistance mandates ongoing surveillance.

Keywords: Asia-Pacific region; Ceftolozane/tazobactam; Gram-negative pathogen; Lower respiratory tract infections; Susceptibility.