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), ceftolozanetazobactam (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 carbapenemresistant Enterobacteriaceae (CRE). Ceftazidime-avibactam demonstrated potent activity against almost all Enterobacteriaceae (94.6% susceptibility; MIC 50 , Յ0.25 mg/liter; MIC 90 , Յ0.25 to Ͼ32 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 ceftazidimeavibactam (71.7%, 66/92). Ceftolozane-tazobactam showed good in vitro activity against Escherichia coli and Proteus mirabilis (MIC 50/90 , Յ0.5/2 mg/liter; 90.5 and 93.8% susceptibility, respectively), and the rates of susceptibility of K. pneumoniae (MIC 50/90 , 2/Ͼ64 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.

<p>Clinical and Molecular Epidemiologic Characteristics of Ceftazidime/Avibactam-Resistant Carbapenem-Resistant <em>Klebsiella pneumoniae</em> in a Neonatal Intensive Care Unit in China</p>

“…Two recent multicenter studies also showed that the vitro activity of CZA against CRKP in adults is high. 25,26 Any decrease in susceptibility to CZA, a novel agent with minimal previous clinical use even in adults, is of concern. To the best of our knowledge, this is the first report of the vitro activity of CZA-resistant CRKP isolated from neonates, including premature neonates.…”

<p>Emergence of Hypervirulent Ceftazidime/Avibactam-Resistant <em>Klebsiella pneumoniae</em> Isolates in a Chinese Tertiary Hospital</p>

“…The use of CAZ/AVI against carbapenem-resistant K. pneumoniae strains has been shown to be very effective to provide a higher clinical cure rate and survival rate in China, the United States, and other European countries. [23][24][25][26] However, increased reports of CAZ/AVI resistance in carbapenem-resistant K. pneumoniae, regardless of prior exposure, is a matter of concern. [27][28][29] A national research about CAZ/AVI resistance in China revealed that MBL production, bla KPC-2 point mutation and high KPC expression played an important role in CAZ/AVI resistance.…”

The latest advances in β-lactam/β-lactamase inhibitor combinations for the treatment of Gram-negative bacterial infections

“…Ceftolozane-tazobactam's strength resides in its potent activity against P. aeruginosa, including multi-drug resistant (MDR) strains with 90-98% of contemporary isolates testing susceptible [17][18][19][20][21][22][23][24][25][26]. Moreover, ceftolozane-tazobactam is a potential carbapenem-sparing treatment regimen against ESBL-producing Enterobacteriaceae [18][19][20][21][22]24]. Ceftolozanetazobactam's activity against ESBL-producing K. pneumoniae as revealed through susceptibility testing is largely lacking [20,21,24,27]; however, in spite of these in vitro results, clinical cure rates are high [28].…”

“…Moreover, ceftolozane-tazobactam is a potential carbapenem-sparing treatment regimen against ESBL-producing Enterobacteriaceae [18][19][20][21][22]24]. Ceftolozanetazobactam's activity against ESBL-producing K. pneumoniae as revealed through susceptibility testing is largely lacking [20,21,24,27]; however, in spite of these in vitro results, clinical cure rates are high [28]. Conversely, the combination is mostly ineffective against Enterobacteriaceae with serine carbapenemases [29][30][31].…”