Pittsburgh—Hospital pharmacists are all in on the use of new, more effective antibiotics that combat carbapenem-resistant Enterobacteriaceae (CRE), but those drugs end up being prescribed only about one-fourth of the time, according to a new study.

The article in Open Forum Infectious Diseases raises questions about clinical and pharmaceutical stewardship practices in U.S. hospitals, especially when infections from the world’s most intractable drug-resistant bacteria are involved.

“The infectious diseases community spent the past decade saying, ‘We need new antibiotics, this is a top priority,’ and now we’re at risk of sounding like the boy who cried wolf,” said lead author Cornelius J. Clancy, MD, associate professor of medicine and director of the mycology program and XDR Pathogen Laboratory in the University of Pittsburgh School of Medicine’s Division of Infectious Diseases. “We have a responsibility to learn why it takes so long for antibiotics to be adopted into practice and figure out what we need to do to ensure the best antibiotics quickly reach the patients who desperately need them.”

The article points out that polymyxins, such as colistin and polymyxin B, have been first-line antibiotics against CRE infections. In addition, new anti-CRE antibiotics—i.e., ceftazidime-avibactam, meropenem-vaborbactam, and plazomicin—have been shown to improve outcomes in CRE-infected patients and reduce toxicity compared with polymyxins. But it is not clear how frequently those agents are being used.

To help answer those questions, the study team conducted an online survey of hospital-based pharmacists in the U.S. to gather their recommendations on treating CRE infections. Based on the survey, ceftazidime-avibactam, meropenem-vaborbactam, or plazomicin were positioned as first-line agents against CRE pneumonia, bacteremia, intra-abdominal infections, and urinary tract infections at 87%, 90%, 83%, and 56% of surveyed U.S. hospitals, respectively.

From February 2018 to January 2019, an estimated 9,437 CRE infections were treated with an IV polymyxin and 7,941 with a new agent, according to the results. Researchers note that those figures represented about 28% (range, 19%-50%) and about 23% (range, 16%-42%) of CRE infections in the U.S., respectively.

“Use of ceftazidime-avibactam, meropenem-vaborbactam, or plazomicin exceeded that of intravenous polymyxins against CRE infections as of December 2018,” the authors write. “Currently, the new drugs are estimated to treat 35% (23% to 62%) of CRE infections in which they were expected to be first-line agents.”

The study decried that use of the new drugs “is less than expected from their positioning at U.S. hospitals. Research on behavioral and economic factors that impact use of new antibiotics is needed, as are financial ‘pull’ incentives that promote an economically viable marketplace.”

Researchers emphasize that pharmacists had good knowledge of the new antibiotics and strong willingness to use them, based on the survey: The drugs were classified as the “first-line” choice against CRE blood infections by 90% of the pharmacists, pneumonia by 87%, intra-abdominal infections by 83%, and urinary tract infections by 56%.

“Clearly hospital-based pharmacists are aware of these antibiotics and believe they are the best choice for the vast majority of CRE infections,” Clancy said.

The researchers note that, even after accounting for CRE infections in which new antibiotics might not be first-choice agents, they determined that use was only about 35% of what was expected based on positioning by hospital-based pharmacists.

Among the reasons cited for slow uptake of the drugs is cost; a 14-day course of the new antibiotics costs between $13,230 and $15,070, compared with $305 to $784 for the old drugs.

“Cost is a limitation, but I’m not convinced it is the sole cause of our findings,” Clancy said. “Clinicians may not be prescribing the new drugs due to concerns about accelerating antibiotic-resistance or because initial studies on their effectiveness were relatively small. We need to get at the root causes of the disconnect between what the doctors prescribe and what the pharmacists we surveyed believe they should be prescribing, and then find a solution.”

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