Ceftazidime-avibactam effective for treating ceftazidime-resistant infections

Last Updated: 2016-04-28

By Will Boggs MD

NEW YORK (Reuters Health) - Ceftazidime in combination with avibactam is effective for treating ceftazidime-resistant urinary tract and intra-abdominal infections, according to results from the REPRISE study.

The prevalence of multidrug-resistant Gram-negative pathogens is increasing worldwide. Avibactam has a broader spectrum of activity than other available beta-lactamase inhibitors.

Dr. Yehuda Carmeli from Tel Aviv Sourasky Medical Center, Israel, and colleagues investigated the efficacy, safety, and tolerability of ceftazidime-avibactam versus best available therapy in a phase 3 study of 333 patients with complicated urinary tract infection or complicated intra-abdominal infection due to ceftazidime-resistant Gram-negative pathogens.

Most (97%) of the 168 patients in the best available therapy group were treated with carbapenem monotherapy, according to the April 20 Lancet Infectious Diseases online report.

Most patients in both groups were infected with Enterobacteriaceae (most commonly Escherichia coli and Klebsiella pneumoniae).

In the combined group, the overall proportions of patients with a clinical cure were 91% with ceftazidime-avibactam and 90% with best available therapy.

Results were similar in the subgroups. For patients with complicated urinary tract infections, the clinical cure rates were 92% with ceftazidime-avibactam versus 94% with best available therapy. For patients with complicated intra-abdominal infections, the clinical cure rates were 80% with ceftazidime-avibactam and 55% with best available therapy.

Microbiological response rates in the urinary tract infection group were higher with ceftazidime-avibactam (82%) than with best available therapy (64%).

Adverse event rates were similar with ceftazidime-avibactam (31%) and best available therapy (39%), with most events classified as mild or moderate in intensity.

"These promising results support the use of ceftazidime-avibactam as a potential alternative to carbapenems in patients with resistant Gram-negative infections," the researchers concluded.

Dr. Florian M.E. Wagenlehner from Justus-Liebig University, Giessen, Germany, who coauthored an accompanying editorial, told Reuters Health by email, "The main message is that ceftazidime-avibactam is noninferior to carbapenems (or best available therapy) in patients with complicated abdominal or urinary infections, although in this study mainly (>90%) urinary infections were studied."

"On the one hand, it has some increased efficacy over carbapenems in bacteria with Klebsiella pneumoniae carbapenemases," he said. "On the other hand, it would well serve as a carbapenem saving strategy to save these last-resort antibiotics."

Dr. Carmeli did not respond to a request for comments.

AstraZeneca funded the trial, provided grants to Dr. Carmeli, and employed the rest of the authors.

SOURCE: http://bit.ly/1VV44Rj and http://bit.ly/1TyMvlT

Lancet Infect Dis 2016.