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

Abstract

Background 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.

Methods We performed a retrospective cohort study of hospital discharges from June 2022 to May 2023 using the Premier Healthcare Database. Antibiotic utilization was ascertained from daily charges. Clinical indication(s) were inferred from International Classification of Diseases, 10th revision, diagnosis codes. Antibiotic therapy was considered definitive if continued >3 days. Piperacillin-tazobactam was used as a comparator.

Results Across 832 hospitals, 3 890 557 admissions (61.9% of all admissions) included an antibiotic prescription. New antibiotics were prescribed in 9768 admissions (0.25% of antibiotic-prescribing admissions) across 537 hospitals. Ceftolozane-tazobactam was prescribed in 4157 admissions (42.6% of 9768), ceftazidime-avibactam in 3660 (37.5%), eravacycline in 1213 (12.4%), cefiderocol in 1060 (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. Forty-six percent (n = 4647/9768) of new antibiotics were started in the first 3 days of hospital admission, and 70% (n = 6799/9768) 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.

Conclusions 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.