Impact of antibiotic use on patient-level risk of death in 36 million hospital admissions in England.

OBJECTIVES: Initiatives to curb hospital antibiotic use might be associated with harm from under-treatment. We examined the extent to which variation in hospital antibiotic prescribing is associated with mortality risk in acute/general medicine inpatients. METHODS: This ecological analysis examined Hospital Episode Statistics from 36,124,372 acute/general medicine admissions (≥16y) to 135 acute hospitals in England, 01/April/2010-31/March/2017. Random-effects meta-regression was used to investigate whether heterogeneity in adjusted 30-day mortality was associated with hospital-level antibiotic use, measured in defined-daily-doses (DDD)/1,000 bed-days. Models also considered DDDs/1,000 admissions and DDDs for narrow-spectrum/broad-spectrum antibiotics, parenteral/oral, and local interpretations of World Health Organization Access, Watch, and Reserve antibiotics. RESULTS: Hospital-level antibiotic DDDs/1,000 bed-days varied 15-fold with comparable variation in broad-spectrum, parenteral, and Reserve antibiotic use. After extensive adjusting for hospital case-mix, the probability of 30-day mortality changed -0.010% (95% CI: -0.064,+0.044) for each increase of 500 hospital-level antibiotic DDDs/1,000 bed-days. Analyses of other metrics of antibiotic use showed no consistent association with mortality risk. CONCLUSIONS: We found no evidence that wide variation in hospital antibiotic use is associated with adjusted mortality risk in acute/general medicine inpatients. Using low-prescribing hospitals as benchmarks could help drive safe and substantial reductions in antibiotic consumption of up-to one-third in this population.