Estimated numbers of all infections (A) and carbapenem-resistant Enterobacteriacae (CRE) infections (B) treated by various agents in the United States. Data are presented as 3-month moving averages of numbers of infections treated intravenously by the indicated antibiotics. Black arrows in A indicate months immediately after the online publication of papers reporting that ceftazidime-avibactam (June 2017, October 2017, July 2018) or meropenem-vaborbactam (October 2018) were significantly more effective and less toxic than colistin or other best available regimens as treatment for CRE infections [7–9, 11]. There is no correlation between publication of these data and changes in the rate of uptake of the respective drug. B shows 3 estimates of numbers of CRE infections treated by intravenous polymyxins. The primary estimate was based on the assumption that 32.5% of all colistin or polymyxin B use before availability of ceftazidime-avibactam was as intravenous treatment of CRE infections (dark blue line in B, labeled as “32.5% baseline”). These data suggested that use of the new agents (ceftazidime-avibactam, meropenem-vaborbactam, plazomicin) against CRE infections exceeded that of intravenous polymyxins in December 2018 (red line). Other estimates were based on assumptions that 20% (gray line) or 45% (light blue, dashed line) of baseline polymyxin use was as intravenous treatment of CRE infections. In the former scenario, use of the new agents against CRE infections has exceeded that of intravenous polymyxins since November 2017. Black arrows in B indicate months that first sales of meropenem-vaborbactam (October 2017) and plazomicin (August 2018) were reported. There was a slight uptick in the overall use of new agents against CRE infections after introduction of meropenem-vaborbactam. Introduction of plazomicin did not impact the trajectory of the usage curve. Estimates of numbers of treated infections were based on the following 14-day regimens: colistin 150 mg twice a day (BID), polymyxin B 1 million units BID (12 500 to 15 000 units/kg BID), ceftazidime-avibactam 2.5 grams 3 times a day (TID), meropenem-vaborbactam 4 grams TID, plazomicin 1125 mg once daily (15 mg/kg per day). Per-vial concentrations of antibiotics are provided in Supplementary Material. (A) Estimated numbers of all infections treated by intravenous polymyxins and new anti-CRE agents. (B) Estimated numbers of CRE infections treated by intravenous polymyxins and new anti-CRE agents. CA, ceftazidime-avibactam; COL, colisitin; MV, meropenem-vaborbactam; PB, polymyxin B; PLZ, plazomicin.