Defining antibiotic use reduction targets for the management of hospital-onset healthcare-associated clostridioides difficile 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.