Alexander Szubert1, Sarah Lou Bailey2, Graham S Cooke3, Tim Peto4, Martin J Llewelyn5, Jonathan D Edgeworth2, A Sarah Walker6, Guy E Thwaites7. 1. Medical Research Council Clinical Trials Unit at University College London, University College London, UK. 2. Guy's and St. Thomas' NHS Foundation Trust, London, UK; Kings College London, London, UK. 3. Imperial College London, UK. 4. Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, UK. 5. Brighton and Sussex Medical School, Brighton, UK. 6. Medical Research Council Clinical Trials Unit at University College London, University College London, UK; Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, UK. 7. Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, UK; Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam. Electronic address: gthwaites@oucru.org.
Abstract
OBJECTIVES:Adjunctive rifampicin did not reduce failure/recurrence/death as a composite endpoint in the ARREST trial of Staphylococcus aureus bacteraemia, but did reduce recurrences. We investigated clinically-defined 14-day treatment failure, and recurrence and S. aureus-attributed/unattributed mortality by 12-weeks to further define their predictors. METHODS: A post-hoc exploratory analysis using competing risks models was conducted to identify sub-groups which might benefit from rifampicin. A points-based recurrence risk score was developed and used to compare rifampicin's benefits. RESULTS:Recurrence was strongly associated with liver and renal failure, diabetes and immune-suppressive drugs (p < 0.005); in contrast, failure and S. aureus-attributed mortality were associated with older age and higher neutrophil counts. Higher SOFA scores predicted mortality; higher Charlson scores and deep-seated initial infection focus predicted failure. Unexpectedly, recurrence risk increased with increasing BMI in placebo (p = 0.04) but not rifampicin (p = 0.60) participants (pheterogeneity = 0.06). A persistent focus was judged the primary reason for recurrence in 23(74%). A 5-factor risk score based on BMI, Immunosuppression, Renal disease, Diabetes, Liver disease (BIRDL) strongly predicted recurrence (p < 0.001). CONCLUSIONS:Rifampicin reduces recurrences overall; those with greatest absolute risk reductions were identified using a simple risk score. Source control and adequate duration of antibiotic therapy remain essential to prevent recurrence and improve outcomes.
RCT Entities:
OBJECTIVES: Adjunctive rifampicin did not reduce failure/recurrence/death as a composite endpoint in the ARREST trial of Staphylococcus aureus bacteraemia, but did reduce recurrences. We investigated clinically-defined 14-day treatment failure, and recurrence and S. aureus-attributed/unattributed mortality by 12-weeks to further define their predictors. METHODS: A post-hoc exploratory analysis using competing risks models was conducted to identify sub-groups which might benefit from rifampicin. A points-based recurrence risk score was developed and used to compare rifampicin's benefits. RESULTS: Recurrence was strongly associated with liver and renal failure, diabetes and immune-suppressive drugs (p < 0.005); in contrast, failure and S. aureus-attributed mortality were associated with older age and higher neutrophil counts. Higher SOFA scores predicted mortality; higher Charlson scores and deep-seated initial infection focus predicted failure. Unexpectedly, recurrence risk increased with increasing BMI in placebo (p = 0.04) but not rifampicin (p = 0.60) participants (pheterogeneity = 0.06). A persistent focus was judged the primary reason for recurrence in 23(74%). A 5-factor risk score based on BMI, Immunosuppression, Renal disease, Diabetes, Liver disease (BIRDL) strongly predicted recurrence (p < 0.001). CONCLUSIONS:Rifampicin reduces recurrences overall; those with greatest absolute risk reductions were identified using a simple risk score. Source control and adequate duration of antibiotic therapy remain essential to prevent recurrence and improve outcomes.
Authors: Oren Gordon; Nadine Peart Akindele; Christina Schumacher; Ann Hanlon; Patricia J Simner; Karen C Carroll; Anna C Sick-Samuels Journal: Pediatr Qual Saf Date: 2022-06-14