Antimicrobial agents are often used for indications not approved by the Food and Drug Administration (FDA). While this can be appropriate at times, they may be used in settings with no published experience. Judicious use of new agents is critical for conserving their utility. This study characterized initial use after FDA approval of select antimicrobial agents in community hospitals without robust antimicrobial stewardship programs (ASP).
Initial use of systemic antimicrobials approved by the FDA since 2014 was retrospectively reviewed at 6 community hospitals (50-350 beds). Up to 10 charts of first use were reviewed per drug at each hospital. Time from FDA approval to first administration was measured for the following agents: ceftazidime-avibactam, ceftolozane-tazobactam, dalbavancin, isavuconazonium, oritavancin, and peramivir. Clinical indications, prescribing service, and empiric uses were recorded.
Mean time from FDA approval to first administration ranged from 12 (tedizolid) to 26 months (dalbavancin). Of frequently used agents (Fig 1), adherence to initial FDA indications ranged from 7% (ceftolozane-tazobactam for complicated urinary tract infection) to 100% (tedizolid for acute bacterial skin and soft tissue infection). Pneumonia (35%) and osteomyelitis (35%) were the most common off-label indications for ceftazidime-avibactam. Pneumonia was the most common off-label indication for ceftolozane-tazobactam (78%). The most common off-label indications for oritavancin were osteomyelitis (14%) and bacteremia (11%). Infectious Diseases was the main prescribing service for all agents (range 74-95%). Use of gram-positive agents was mostly empiric whereas gram-negative agents were targeted against specific pathogens.
Newly approved antimicrobial agents were used at these 6 community hospitals within 1-2 years after FDA approval. Agents with primarily gram-positive activity were more often used for FDA approved indications. Given frequent use of novel gram-negative agents for pneumonia, there is need for early trials to determine their role for this indication. In the meantime, ASPs should consider off-label indications such as pneumonia when developing local criteria for use.