Results from the China Antimicrobial Surveillance Network (CHINET) in 2017 of the In Vitro Activities of Ceftazidime-Avibactam and Ceftolozane-Tazobactam against Clinical Isolates of Enterobacteriaceae and Pseudomonas aeruginosa

Abstract

The in vitro activities of ceftazidime-avibactam (CZA), ceftolozane-tazobactam (C-T), and comparators were determined for 1,774 isolates of Enterobacteriaceae and 524 isolates of Pseudomonas aeruginosa collected by 30 medical centers from the China Antimicrobial Surveillance Network (CHINET) in 2017. Antimicrobial susceptibility testing was performed by the CLSI broth microdilution method, and bla_KPC and bla_NDM were detected by PCR for all carbapenem-resistant Enterobacteriaceae (CRE). Ceftazidime-avibactam demonstrated potent activity against almost all Enterobacteriaceae (94.6% susceptibility; MIC₅₀, ≤0.25 mg/liter; MIC₉₀, ≤0.25 to >32 mg/liter) and good activity against P. aeruginosa (86.5% susceptibility; MIC_50/90, 2/16 mg/liter). Among the CRE, 50.8% (189/372 isolates) were positive for bla_KPC-2, which mainly existed in ceftazidime-avibactam-susceptible Klebsiella pneumoniae isolates (92.1%, 174/189). Among the CRE, 17.7% (66/372 isolates) were positive for bla_NDM, which mainly existed in strains resistant to ceftazidime-avibactam (71.7%, 66/92). Ceftolozane-tazobactam showed good in vitro activity against Escherichia coli and Proteus mirabilis (MIC_50/90, ≤0.5/2 mg/liter; 90.5 and 93.8% susceptibility, respectively), and the rates of susceptibility of K. pneumoniae (MIC_50/90, 2/>64 mg/liter) and P. aeruginosa (MIC_50/90, 1/8 mg/liter) were 52.7% and 88.5%, respectively. Among the CRE strains, 28.6% of E. coli isolates and 85% of K. pneumoniae isolates were still susceptible to ceftazidime-avibactam, but only 7.1% and 1.9% of them, respectively, were susceptible to ceftolozane-tazobactam. The rates of susceptibility of the carbapenem-resistant P. aeruginosa isolates to ceftazidime-avibactam (65.7%) and ceftolozane-tazobactam (68%) were similar. Overall, both ceftazidime-avibactam and ceftolozane-tazobactam were highly active against clinical isolates of Enterobacteriaceae and P. aeruginosa recently collected across China, and ceftazidime-avibactam showed activity superior to that of ceftolozane-tazobactam against Enterobacteriaceae, whereas ceftolozane-tazobactam showed a better effect against P. aeruginosa.

Keywords: Enterobacteriaceae; Pseudomonas aeruginosa; blaKPC; blaNDM; ceftazidime-avibactam; ceftolozane-tazobactam; multicenter study.

FIG 1

Distribution of ceftazidime-avibactam MICs (x axis; in milligrams per liter) against Enterobacteriaceae and Pseudomonas aeruginosa clinical isolates. (a) Enterobacteriaceae; (b) bla_NDM-positive Enterobacteriaceae; (c) bla_KPC-positive Enterobacteriaceae; (d) Pseudomonas aeruginosa. Numbers on the y axis are in percent.

FIG 2

Distribution of ceftolozane-tazobactam MICs (x axis; in milligrams per liter) against Enterobacteriaceae and Pseudomonas aeruginosa clinical isolates. (a) Enterobacteriaceae; (b) bla_NDM-positive Enterobacteriaceae; (c) bla_KPC-positive Enterobacteriaceae; (d) Pseudomonas aeruginosa. Numbers on the y axis are in percent.