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Estimating the Treatment of Carbapenem-Resistant Enterobacteriaceae Infections in the United States Using Antibiotic Prescription Data.

Background
Polymyxins (colistin, polymyxin B) have been first-line antibiotics against carbapenem-resistant Enterobacteriaceae (CRE) infections. New anti-CRE antibiotics (ceftazidime-avibactam, meropenem-vaborbactam, plazomicin) improve outcomes in CRE-infected patients and reduce toxicity compared with polymyxins. It is unclear how widely polymyxins and newer agents are used to treat CRE infections.


Methods
We conducted an online survey of US hospital-based pharmacists to determine antibiotic positioning against CRE infections. Numbers of all infections and CRE infections treated with different antibiotics in the United States were determined using IQVIA prescription data and Driving Re-investment in Research and Development and Responsible Antibiotic Use (DRIVE-AB) estimates of CRE infections.


Results
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 US hospitals, respectively. From February 2018 to January 2019, an estimated 9437 and 7941 CRE infections were treated with an intravenous polymyxin or new agent, respectively; these figures represented ~28% (range, 19%-50%) and ~23% (range, 16%-42%) of CRE infections in the United States. Use of ceftazidime-avibactam, meropenem-vaborbactam, or plazomicin exceeded that of intravenous polymyxins against CRE infections as of December 2018. 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.


Conclusions
New anti-CRE agents recently surpassed intravenous polymyxins as treatment for CRE infections, but use is less than expected from their positioning at US 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.