In the JournalsPerspective

Clinical uptake of new anti-CRE agents ‘steady but slow’

Cornelius (Neil) J. Clancy

Researchers estimated that approximately 23% of carbapenem resistant Enterobacteriaceae, or CRE, infections in the United States are treated with new anti-CRE antibiotics compared with about 28% of infections treated with IV polymyxins.

“New antibiotics that are active against carbapenem-resistant Enterobacteriaceae (CRE) have been shown to improve outcomes and reduce toxicity among CRE-infected patients, compared to polymyxins — colistin, polymyxin B — or other agents used previously,” Cornelius (Neil) J. Clancy, MD, associate professor of medicine and director of the XDR pathogen lab and mycology program at the University of Pittsburgh and chief of the infectious diseases section at the VA Pittsburgh Healthcare System, told Infectious Disease News.

“However, the use of new anti-CRE agents — ceftazidime-avibactam, meropenem-vaborbactam, plazomicin — against CRE infections in the United States only surpassed that of IV polymyxins for the first time in December 2018. Overall clinical uptake of the new drugs has been steady but slow despite their effectiveness.”

Clancy and colleagues conducted an online survey of hospital-based infectious disease pharmacists in the U.S. to determine how many positioned new anti-CRE agents as first-line therapy and collected responses between Nov. 27 through Dec. 18, 2018. They used IQVIA prescription data and estimates of CRE infections from the DRIVE-AB project to calculate the number of CRE infections in the U.S. and how they were treated during a recent 12-month period.

According to the survey results, ceftazidime-avibactam, meropenem-vaborbactam or plazomicin were positions as first-line treatment against CRE bacteremia in 90% of hospitals. The same was true in 87% of hospitals for CRE pneumonia, 83% for CRE intra-abdominal infections and 56% for CRE UTIs.

Between February 2018 and January 2019, the researchers estimated that approximately 9,437 CRE infections — or about 28% of CRE infections in the U.S. — were treated with an IV polymyxin compared with approximately 7,941 infections — or about 23% of CRE infections — that were treated with new anti-CRE agents.

Clancy and colleagues estimated that, currently, the new antibiotics are used to treat about 35% of CRE infections “in which they were expected to be first-line agents.”

Clancy said the findings demonstrate a “discordance between positioning of new anti-CRE drugs as a first-line agents against CRE infections at U.S. hospitals ... and actual use of the drugs.”

“It is important to understand the reasons for this discordance, in particular whether high costs of the new drugs or hospital stewardship practices play roles,” he said.

He highlighted ways in which infectious disease clinicians can and should help shape public policy, educate providers and develop “timely” guidelines.

“At this point, guidelines should explicitly state that polymyxins are not standard first-line agents against CRE infections,” Clancy said. “Research is needed on behavioral and economic factors that impact use of these and other new antibiotics. We also need more precise national data on numbers and treatment of infections by CRE and other drug-resistant bacteria and fungi.” – by Marley Ghizzone

Disclosures: Clancy reports numerous ties with industry. Please see the study for all other authors’ relevant financial disclosures.

 

Cornelius (Neil) J. Clancy

Researchers estimated that approximately 23% of carbapenem resistant Enterobacteriaceae, or CRE, infections in the United States are treated with new anti-CRE antibiotics compared with about 28% of infections treated with IV polymyxins.

“New antibiotics that are active against carbapenem-resistant Enterobacteriaceae (CRE) have been shown to improve outcomes and reduce toxicity among CRE-infected patients, compared to polymyxins — colistin, polymyxin B — or other agents used previously,” Cornelius (Neil) J. Clancy, MD, associate professor of medicine and director of the XDR pathogen lab and mycology program at the University of Pittsburgh and chief of the infectious diseases section at the VA Pittsburgh Healthcare System, told Infectious Disease News.

“However, the use of new anti-CRE agents — ceftazidime-avibactam, meropenem-vaborbactam, plazomicin — against CRE infections in the United States only surpassed that of IV polymyxins for the first time in December 2018. Overall clinical uptake of the new drugs has been steady but slow despite their effectiveness.”

Clancy and colleagues conducted an online survey of hospital-based infectious disease pharmacists in the U.S. to determine how many positioned new anti-CRE agents as first-line therapy and collected responses between Nov. 27 through Dec. 18, 2018. They used IQVIA prescription data and estimates of CRE infections from the DRIVE-AB project to calculate the number of CRE infections in the U.S. and how they were treated during a recent 12-month period.

According to the survey results, ceftazidime-avibactam, meropenem-vaborbactam or plazomicin were positions as first-line treatment against CRE bacteremia in 90% of hospitals. The same was true in 87% of hospitals for CRE pneumonia, 83% for CRE intra-abdominal infections and 56% for CRE UTIs.

Between February 2018 and January 2019, the researchers estimated that approximately 9,437 CRE infections — or about 28% of CRE infections in the U.S. — were treated with an IV polymyxin compared with approximately 7,941 infections — or about 23% of CRE infections — that were treated with new anti-CRE agents.

Clancy and colleagues estimated that, currently, the new antibiotics are used to treat about 35% of CRE infections “in which they were expected to be first-line agents.”

Clancy said the findings demonstrate a “discordance between positioning of new anti-CRE drugs as a first-line agents against CRE infections at U.S. hospitals ... and actual use of the drugs.”

“It is important to understand the reasons for this discordance, in particular whether high costs of the new drugs or hospital stewardship practices play roles,” he said.

He highlighted ways in which infectious disease clinicians can and should help shape public policy, educate providers and develop “timely” guidelines.

“At this point, guidelines should explicitly state that polymyxins are not standard first-line agents against CRE infections,” Clancy said. “Research is needed on behavioral and economic factors that impact use of these and other new antibiotics. We also need more precise national data on numbers and treatment of infections by CRE and other drug-resistant bacteria and fungi.” – by Marley Ghizzone

Disclosures: Clancy reports numerous ties with industry. Please see the study for all other authors’ relevant financial disclosures.

 

    Perspective
    Keith S. Kaye

    Keith S. Kaye

    There are new agents that can safely and effectively treat CRE. Clinicians should be aware of their availability.  

    Lack of knowledge about these agents — their availability and when they are appropriate to prescribe — contributes to the low use of anti-CRE drugs. Also, their cost is high.

    Additional clinical studies and reports regarding treatment of patients with CRE infection with these new agents is needed. Although some data are available, there is relatively little.

    Also, [pharmacokinetic] evaluations of these agents in special populations, such as subjects with septic shock, meningitis and obesity, are warranted.

    The use of newer agents active against resistant gram-negative bacteria is exciting but complex. One drug does not treat all resistant gram-negative bacteria. Activity among CRE varies with newer agents, even varies by mechanism of carbapenem resistance. The physician should work with the antimicrobial stewardship team to help determine where these drugs best fit in the management of his or her patients.  

    • Keith S. Kaye, MD, MPH
    • Infectious Disease News Editorial Board member
      Professor of internal medicine and director of clinical research
      Division of infectious diseases
      University of Michigan Medical School

    Disclosures: Kaye reports serving as a consultant for Allergan, Melinta and Xellia.