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.