2251. Estimating the Need for Novel Gram-Negative Active Antibiotics in US Hospitals

BACKGROUND: Assessing the unmet need for novel antibiotics could inform appropriate utilization, enrollment in trials and ensure balance in aligning incentives and investments in therapeutic development. METHODS: The Cerner Healthfacts electronic health record repository was queried to identify inpatient treatment opportunities for Gram-negative active agents (GNAA) displaying either difficult-to-treat resistance (DTR; resistance to all β-lactams including carbapenems and fluoroquinolones) or extended-spectrum cephalosporin resistance (ECR). The former was quantified by aggregating episodes of confirmed DTR infection (i.e., DTR strain isolated and concomitant antibiotic(s) received) or suspected (i.e., 1–2 days of empiric colistin/polymyxin-B or aminoglycosides and no DTR pathogen isolated). Aggregate days of therapy (DOT) were reported as a range, multiplying episodes by site-specific or uniform 14-day treatment durations, respectively. Recursive partition and cluster analyses were performed for hospital characteristics and contributions of outbreaks to DTR treatment opportunities, respectively. RESULTS: Between 2009 and 2015, across 2,996,271 encounters, 1,352 episodes of potential targeted treatment were identified, which combined with empiric treatment episodes, represent 39–138 DOT/10,000 encounters for a DTR-GNAA. Similarly, 9,535 episodes of potential targeted therapy for an ECR-GNAA were identified (representing 211-466 DOT/10,000 encounters). The most common candidate site and pathogens for DTR-GNAA were lower respiratory and A. baumannii and P. aeruginosa respectively; DTR bloodstream infections displayed the highest crude mortality at 45%. Enterobacteriaceae urinary infections dominated the ECR group. Teaching hospitals with ≥100 beds were the most likely to encounter a DTR infection; potential outbreaks contributed to 10.6% of DTR treatment opportunities. CONCLUSION: The candidate population for new antibacterials directed against highly resistant GN infections with limited treatment options is small but critical, indicating a role for non-revenue-based strategies to develop more effective antibiotics, as well as mechanisms to support trials that address real-world unmet needs. [Image: see text] [Image: see text] [Image: see text] [Image: see text] DISCLOSURES: All authors: No reported disclosures.