Anti-CRE Agents Are Used Less Widely Than Expected After FDA Approval

enterobacteria, petri dish, bacteria
enterobacteria, petri dish, bacteria
New antibiotics indicated to treat carbapenem-resistant Enterobacteriaceae infections were prescribed in only 35% of CRE infections.

New antibiotics indicated to treat carbapenem-resistant Enterobacteriaceae (CRE) infections were prescribed in only 35% of CRE infections, according to a study published in Open Forum Infectious Diseases.

To compare intravenous use of polymyxins (colistin, polymyxin B), the longstanding first-line antibiotic for CRE infections, with newer agents that have been shown to be more effective and less toxic, researchers conducted an online survey of hospital-based pharmacists to evaluate first-line therapy against various CRE infections at individual hospital. Choices included the aforementioned polymyxins, as well as ceftazidime-avibactam, meropenem-vaborbactam, plazomicin. Participants also provided information on percentages of intravenous polymyxin use at their hospital that were directed against CRE and other multidrug-resistant bacterial infections.

Survey respondents from 41 states and Puerto Rico provided data on individual questions. Ceftazidime-avibactam, meropenem-vaborbactam, or plazomicin were positioned as the first-line antibiotic against CRE pneumonia, bacteremia, and intra-abdominal infections by 87%, 90%, and 83% of respondents, respectively. However, in 56% of reponses, pharmacists indicated the use of 1 of these new antibiotics for the treatment of a urinary tract infection. Respondents indicated that 26.5% of intravenous polymyxin use at their hospitals was directed against CRE infections.

In the year before ceftazidime-avibactam was introduced to the market (April 2014 through March 2015), an estimated 17,450 CRE infections were treated with intravenous polymyxin. The corresponding figure for the 12 months ending in January 2019 were 9437 CRE infections, of which an estimated 7941 cases were treated with ceftazidime-avibactam, meropenem-vaborbactam, or plazomicin.

These estimates, combines with data from an earlier study (DRIVE-AB) suggest that 28% (range 19%-50%) and 23% (range 16%-42%) of CRE infections in the United States were treated with intravenous polymyxin and new anti-CRE agents, respectively, over the 12 months ending in January 2019. After adjusting for cases in which another antibiotic may have been preferred over a new anti-CRE agent, researchers estimated that new anti-CRE antibiotics were used against 35% of CRE infections, in cases wherein this class of medication was expected to be the first-line agents.

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“A confirmation that new anti-CRE agents are used much less widely than expected would support our call for (1) an examination of clinical and stewardship practices at US hospitals and (2) research into behavioral and economic factors that have led to sluggish drug uptake,” the researchers concluded. “Now, the need is for ‘pull’ incentives that fairly recognize the societal value of effective antibiotics, reward manufacturers after agents with activity against priority pathogens enter the marketplace, and delink revenues from volume of sales.”

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.


Clancy CJ, Potoski BA, Buehrle D, Nguyen MH. Estimating the treatment of carbapenem-resistant enterobacteriaceae infections in the United States using antibiotic prescription data [published online July 28, 2019]. _Open Forum Infect Dis. _doi: 10.1093/ofid/ofz344