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New antimicrobials demonstrate ‘good activity’ at long-term acute-care hospitals
Two new antimicrobials with potential utility for resistant isolates at long-term acute-care hospitals demonstrated different in vitro activities against ceftazidime-nonsusceptible Pseudomonas aeruginosa and carbapenem-resistant Enterobacteriaceae, or CRE, according to research findings published in Clinical Microbiology and Infectious Diseases.
“The population we looked at is important because it’s not the general population, it’s the long-term acute-care hospital population,” Ellie J.C. Goldstein, MD, Infectious Disease News Editorial Board member, clinical professor of medicine at the University of California, Los Angeles School of Medicine, and director of the R.M. Alden Research Laboratory in Santa Monica, California, said in an interview. “Patients in long-term acute-care facilities are considered reservoirs for resistant isolates, so this is a more focused study.”
According to the study, choosing appropriate empirical therapy for the treatment of multidrug-resistant organisms can be “unpredictable and problematic,” but when done correctly it can reduce mortality. Within the last 2 years, ceftazidime-avibactam and ceftolozane-tazobactam — marketed as Avycaz and Zerbaxa in the United States — were approved to treat complicated intra-abdominal infections, and they demonstrated in vitro activity against Enterobacteriaceae and P. aeruginosa. Goldstein said that previously, studies of the in vitro activity were performed by “reference laboratories or laboratories that report single-center isolates.” Instead, he and colleagues looked to ascertain “real world” information about the in vitro activity of the two antimicrobials.
Between March 2015 and December 2015, all isolates from 12 regional southern California long-term acute care hospitals were submitted for testing to a centralized microbiology laboratory. Selected strains that were isolated from extended-spectrum-beta-lactamases (ESBL) and carbapenem-resistant Enterobacteriaceae (CRE), as well as ceftazidime nonsusceptible P. aeruginosa were the subject of further study. Goldstein and colleagues tested the activity of ceftazidime-avibactam and ceftolozane-tazobactam against the resistant P. aeruginosa isolates, but only ceftazidime-avibactam against CRE.
ESBL and CRE strains were found to be susceptible to ceftazidime-avibactam, according to the study. The researchers found that the minimum inhibitory concentration (MIC90) for ceftazidime-avibactam was 4/4 µg/mL for a 98.8% susceptibility rate with carbapenem-resistant Klebsiella pneumoniae. When Goldstein and colleagues assessed ceftazidime-avibactam in vitro, they found that it was active against CRE. However, ceftolozane-tazobactam demonstrated better in vitro activity against ceftazidime-resistant P. aeruginosa than ceftazidime-avibactam. There were no isolates that were susceptible to ceftazidime-avibactam but resistant to ceftolozane-tazobactam. Ceftazidime-avibactam demonstrated 72% susceptibility against ceftazidime-resistant P. aeruginosa, whereas ceftolozane-tazobactam had an 88% susceptibility rate.
Goldstein and colleagues reported that the two antimicrobials have “different potential uses” in long-term acute-care hospitals. They recommend continued surveillance and further study of long-term acute-care hospital isolates.
“Each drug has a different profile,” Goldstein said. “One is better against CRE and one is better against Pseudomonas. You can’t interchange them if you’re looking for empirical coverage because each one has a different niche and different utility.” – by Marley Ghizzone
Disclosures: Goldstein serves on advisory boards for Bio-K+, Daiichi Sankyo, Merck, Novartis, Paratek Pharmaceuticals, Sanofi-Aventis, Shionogi and Summit Corp.; speakers bureaus for Allergan, Bayer, The Medicines Company and Merck; and has received research grants from numerous pharmaceutical companies.