Ceftolozane-tazobactam activity against drug-resistant Enterobacteriaceae and Pseudomonas aeruginosa causing healthcare-associated infections in Australia and New Zealand: Report from an Antimicrobial Surveillance Program (2013-2015)

M A Pfaller; D Shortridge; H S Sader; R K Flamm; M Castanheira

doi:10.1016/j.jgar.2017.05.025

Ceftolozane-tazobactam activity against drug-resistant Enterobacteriaceae and Pseudomonas aeruginosa causing healthcare-associated infections in Australia and New Zealand: Report from an Antimicrobial Surveillance Program (2013-2015)

J Glob Antimicrob Resist. 2017 Sep:10:186-194. doi: 10.1016/j.jgar.2017.05.025. Epub 2017 Jul 19.

Authors

M A Pfaller¹, D Shortridge², H S Sader³, R K Flamm³, M Castanheira³

Affiliations

¹ JMI Laboratories, North Liberty, IA, USA; University of Iowa College of Medicine, Iowa City, IA, USA.
² JMI Laboratories, North Liberty, IA, USA. Electronic address: dee-shortridge@jmilabs.com.
³ JMI Laboratories, North Liberty, IA, USA.

PMID: 28735046
DOI: 10.1016/j.jgar.2017.05.025

Abstract

Objectives: To evaluate the in vitro activity of ceftolozane-tazobactam and comparator agents tested against isolates of Enterobacteriaceae and Pseudomonas aeruginosa from patients in Australia and New Zealand with healthcare-associated infection.

Methods: A total of 1459 gram-negative organisms (440 P. aeruginosa and 1019 Enterobacteriaceae) were consecutively collected from 11 medical centers located in Australia and New Zealand. The organisms were tested for susceptibility by broth microdilution methods as described by the CLSI M07-A10 document and the results interpreted according to EUCAST and CLSI breakpoint criteria.

Results: Ceftolozane-tazobactam (MIC_50/90, 0.25/0.5μg/mL; 97.7/95.9% susceptible [CLSI/EUCAST]), meropenem (MIC_50/90, ≤0.06/≤0.06μg/mL; 99.8/99.9% susceptible [CLSI/EUCAST]) and amikacin (MIC_50/90, 2/4μg/mL; 99.8/99.6% susceptible [CLSI/EUCAST]) were the most active compounds tested against Enterobacteriaceae. Enterobacteriaceae isolates displayed susceptibility rates to other β-lactam agents ranging from 95.3/94.4% for cefepime, 94.1/91.4% for piperacillin-tazobactam, and 93.3/91.5% for ceftazidime using CLSI/EUCAST breakpoints. Among the Enterobacteriaceae isolates tested, 0.1% were CRE and 6.6% exhibited an ESBL non-CRE phenotype. Whereas ceftolozane-tazobactam showed good activity against ESBL non-CRE phenotype strains of Enterobacteriaceae (MIC_50/90, 0.5/2μg/mL), it lacked useful activity (MIC, >32μg/mL) against the single isolate with a CRE resistant phenotype. Ceftolozane-tazobactam was the most potent (MIC_50/90, 0.5/2μg/mL) β-lactam agent tested against P. aeruginosa isolates, inhibiting 95.7% at an MIC of ≤4μg/mL.

Conclusions: Ceftolozane-tazobactam was the most active β-lactam agent tested against P. aeruginosa and demonstrated higher in vitro activity than currently available cephalosporins and piperacillin-tazobactam when tested against Enterobacteriaceae.

Keywords: Australia; Ceftolozane–tazobactam; Drug resistance; Enterobacteriaceae; New Zealand; P. aeruginosa; Surveillance.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Anti-Bacterial Agents
Australia
Cephalosporins / pharmacology*
Cross Infection / microbiology*
Drug Resistance, Multiple, Bacterial / drug effects*
Enterobacteriaceae / drug effects*
Enterobacteriaceae / isolation & purification
Enterobacteriaceae Infections / microbiology
Humans
Microbial Sensitivity Tests
New Zealand
Pseudomonas Infections / microbiology
Pseudomonas aeruginosa / drug effects*
Pseudomonas aeruginosa / isolation & purification
Tazobactam / pharmacology*

Substances

Anti-Bacterial Agents
Cephalosporins
ceftolozane, tazobactam drug combination
Tazobactam