Defining antibiotic use reduction targets for the management of hospital-onset healthcare-associated Clostridioides difficile infection: results of the multi-center 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 (defined daily doses (DDD)/1000 occupied bed-days (OBD)) were identified: AAH- fluoroquinolones 62.3, macrolides 254.6; CAH- co-amoxiclav 75.8, carbapenems 16.1; PGH- co-amoxiclav 251.3, macrolides 129.2; SJUH- clindamycin 14.2, fluoroquinolones 128.3. Risk scores for exceeding high HOHA-CDI incidence were determined, supporting 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.