New Kids on the Block: Estimating Use of Next Generation Gram-negative Antibiotics Across Greater than 700 Hospitals in the United States

In recent years, new broad-spectrum antibiotics targeting Gram-negative organisms have been introduced, including cefiderocol, ceftazidime-avibactam, ceftolozane-tazobactam, eravacycline, imipenem-relebactam, omadacycline and meropenem-vaborbactam. This study aimed to describe new antibiotic use across a large national cohort.We performed a retrospective cohort study of hospital discharges from June 2022-May 2023 using the PINC-AI Database. Antibiotic utilization was ascertained from daily charges. Clinical indication(s) were inferred from ICD-10 diagnosis codes. Antibiotic therapy was considered definitive if continued >3 days. Piperacillin-tazobactam was used as a comparator.Across 832 hospitals, 3,890,557 admissions (61.9% of all admissions) included an antibiotic prescription. New antibiotics were prescribed in 9,768 admissions (0.25% of antibiotic-prescribing admissions) across 537 hospitals. Ceftolozane-tazobactam was prescribed in 4,157 admissions (42.6% of 9,768), ceftazidime-avibactam in 3,660 (37.5%), eravacycline in 1,213 (12.4%), cefiderocol in 1,060 (10.9%), meropenem-vaborbactam) in 456 (4.7%), omadacycline in 104 (1.1%), and imipenem-relebactam in 99 (1.0%). In contrast, piperacillin-tazobactam was prescribed in 731,719 (18.8%) and colistin in 570 (0.01%) admissions. 46% (n=4,647/9,768) of new antibiotics were started in the first 3 days of hospital admission, and 70% (n=6,799/9,768) were used as definitive therapy. Sepsis (76%), pneumonia (46%), and urinary tract infection (39%) were the most common clinical indications. On average, patients treated with new antibiotics had 8 more comorbid conditions than patients receiving piperacillin-tazobactam.Ceftazidime-avibactam and ceftolozane-tazobactam remain the most frequently prescribed new antibiotics, with uptake of subsequently approved agents trailing. New antibiotics are most commonly used as treatment for sepsis among patients with multiple comorbidities.