Avycaz reduces risk for death from CRE by 23% compared with colistin
In an observational study, patients with carbapenem-resistant Enterobacteriaceae — or CRE — infections who were started on Avycaz had a 23% reduced risk for death compared with patients who were started on colistin.
Moreover, patients started on Avycaz (ceftazidime/avibactam, Allergan) had a 64% chance of a better outcome compared with patients treated with colistin, David van Duin, MD, PhD, associate professor of medicine at the University of North Carolina, and colleagues reported in Clinical Infectious Diseases.
“Ceftazidime/avibactam, as a beta-lactam agent, not surprisingly appears to perform much better than colistin in the treatment of CRE infections,” van Duin told Infectious Disease News.
Colistin fell out of favor decades ago because of its toxicity but has been used recently as a last resort to treat multidrug-resistant infections. The first transferable gene for resistance to colistin, mcr-1, was discovered 2 years ago and has been detected worldwide in animals and people, including in the United States.
“Polymyxins were largely abandoned in the 1950s for limited efficacy and toxicity concerns in favor of newer drugs, including aminoglycosides,” van Duin said. “It is therefore not surprising that if you have a beta-lactam agent that actually works in vitro, it will result in better outcomes for your patients. I think with new agents for CRE, colistin resistance — at least in Enterobacteriaceae — will be of mostly academic interest, with a limited clinical impact.”
Van Duin and colleagues studied the outcomes of 137 patients with cultured CRE infections who were initially treated with either ceftazidime/avibactam or colistin. The patients were part the CRACKLE study — the consortium on resistance against carbapenems in patients with Klebsiella and other Enterobacteriaceae. They were from 18 hospitals, predominantly in the Great Lakes region, and received treatment between Dec. 24, 2011, to May 1, 2016.
For just over 3 years of the study, only data on patients with carbapenem-resistant K. pneumoniae were collected. After that, all patients with any CRE were included. The most common infections were those of the bloodstream or respiratory system.
According to van Duin and colleagues, among 38 patients first treated with ceftazidime/avibactam, the inverse probability of treatment weighting (IPTW)-adjusted all-cause hospital mortality at 30 days after starting treatment was 9% compared with 32% in 99 patients treated first with colistin, a difference of 23% (95% bootstrap CI, 9% to 35%). Patients in the ceftazidime/avibactam arm had an IPTW-adjusted 64% probability of a better outcome than those started on colistin (95% CI, 57% to 71%) — a key measure of superiority, van Duin and colleagues noted.
“The importance of patient-centered outcomes that go beyond mortality is increasingly recognized,” van Duin and colleagues wrote. “Recently, several states of health were deemed by patients to be even worse than death, suggesting that patient-centered quality-of-life outcomes are important to measure.”
The results show that ceftazidime/avibactam “may be a reasonable alternative to colistin” to treat K. pneumoniae carbapenemase-producing CRE infections, but van Duin and colleagues said their findings require confirmation in a randomized controlled trial.
“The only reason we did this comparison is because randomized controlled trial comparative data are not available,” van Duin said. “Whenever treatments are compared in observational studies, caution should be applied as different patients are treated differently for a reason. We have tried to adjust for this through statistical methods, but you can only adjust for what you can measure. This is why randomization is key.”
Van Duin also noted that reports of ceftazidime/avibactam resistance have already emerged. The resistance has been classified as “rapid” and “concerning” by other researchers. – by Gerard Gallagher
Disclosure: Van Duin reports serving on advisory boards for Allergan, Achaogen, Shionogi, Tetraphase, Sanofi-Pasteur, MedImmune and Astellas, and receiving research funding from Steris Inc. and Scynexis. Please see the study for all other authors’ relevant financial disclosures.