Defining antibiotic use reduction targets for the management of hospital-onset healthcare-associated <i>clostridioides difficile</i> infection: results of the multi-centre TARGET-A project in four UK hospitals

BACKGROUND: Nonlinear analyses show promise for determining antibiotic use thresholds linked to antimicrobial resistance (AMR). An approach that allows aggregation of results from multiple models to capture context-specific AMR dynamics is needed to improve predictive accuracy and define realistic antibiotic use thresholds to reduce AMR. METHODS: We conducted TARGET-A, a retrospective multicentre ecological modeling study in four UK hospitals (2020-2024), applying a threshold-logistic ensemble consensus modeling approach to identify hospital-level antibiotic use thresholds and risk scores associated with increasing hospital-onset, healthcare-associated Clostridioides difficile infection (HOHA-CDI) incidence. RESULTS: Analysis set the cutoffs for critically high HOHA-CDI incidence at: Antrim Area Hospital (AAH), 75th percentile; Craigavon Area Hospital (CAH), 80th percentile; Pinderfields General Hospital (PGH), 82.5th percentile; St James's University Hospital (SJUH), 77.5th percentile. Antibiotic use thresholds, expressed as defined daily doses (DDD) per 1,000 occupied bed-days (OBD), were identified as follows: AAH- fluoroquinolones, 62.3, and macrolides, 254.6; CAH- co-amoxiclav, 75.8, and carbapenems, 16.1; PGH- co-amoxiclav, 251.3, and macrolides, 129.2; and SJUH- clindamycin, 14.2, and fluoroquinolones, 128.3. Risk scores for exceeding the high HOHA-CDI incidence were determined to support early-warning alerts. A consensus approach was developed to establish attainable antibiotic use thresholds. CONCLUSIONS: This approach provides a framework to define hospital-level quantitative antibiotic use targets to control HOHA-CDI incidence. Further validation is needed in prospective interventional studies.