Ceftazidime-avibactam was highly active against a large collection of gram-negative bacteria isolated from patients with complicated urinary tract infections (cUTI) in hospitals in the United States, according to a poster presented at IDWeek 2019, held from October 2 to October 6, in Washington, DC.

The current study evaluated the antimicrobial activity of recently approved β-lactamase inhibitor combinations and comparators against gram-negative bacteria isolates from consecutively collected from patients with cUTIs in 65 US hospitals in 2018. The 4371 gram-negative organisms were tested for susceptibility to these antibiotics using reference broth microdilution methods. In addition, whole genome sequencing was used to screen Enterobacterales with elevated cephalosporin minimum inhibitory concentrations for β-lactamase-encoding genes.

Escherichia coli (44.5%), Klebsiella pneumoniae (19.6%), Proteus mirabilis (6.7%), and Pseudomonas aeruginosa (5.3%) were the most common gram-negative organisms. The most active agents against Enterobacterales were ceftazidime-avibactam (99.9% susceptibility), amikacin (99.7% susceptibility), and meropenem (99.4% susceptibility).

Extended spectrum β-lactamase (ESBL) genes were identified in 7.6% Enterobacterales isolates, including CTX-M-15 (63% of ESBL producers), OXA1/OXA-30 (39%), SHV-type (30%), and other CTX-M types (25%). Approximately 40% of ESBL producers had >2 ESBL genes, primarily CTX-M-type and OXA-type (37% of isolates).

The most active agents against ESBL producers were ceftazidime-avibactam (100.0% susceptibility), amikacin (99.7% susceptibility), and meropenem (99.4% susceptibility), while ceftolozane-tazobactam was active against 90.6% of ESBL producers and piperacillin-tazobactam was active against 84.8%. The only agents exhibiting good activity against carbapenem-resistant Enterobacterales were ceftazidime-avibactam, colistin, and tigecycline with susceptibilities of 87.0%, 87.0%, and 95%, respectively.

Further, 0.07% Enterobacterales isolates were ceftazidime-avibactam resistant, all of which had a metallo-β-lactamase gene. The most active β-lactams tested against P aeruginosa were ceftazidime-avibactam and ceftolozane-tazobactam (97.0% and 99.1% susceptibility, respectively).

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Study investigators concluded, “[ceftazidime-avibactam] was highly active against a large collection of contemporary [Gram-negative] bacteria isolated from patients with cUTIs in US hospitals and provided greater coverage than the agents currently available in the US to treat cUTIs.”

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.

Reference

Sader H, Flamm R, Castanheira M, Mendez R. Comparison of ceftazidime-avibactam, ceftolozane-tazobactam, piperacillin-tazobactam, and meropenem activities when tested against gram-negative organisms isolated from complicated urinary tract infections. Poster presented at: IDWeek 2019; October 2-6, 2019; Washington, DC. Poster 1436.