Predictors of recurrence, early treatment failure and death from Staphylococcus aureus bacteraemia: observational analyses within the ARREST trial
File(s)
Published version
Author(s)
Type
Journal Article
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.
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.
Date Issued
2019-10-01
Date Acceptance
2019-08-03
Citation
Journal of Infection, 2019, 79 (4), pp.332-340
ISSN
0163-4453
Publisher
Elsevier BV
Start Page
332
End Page
340
Journal / Book Title
Journal of Infection
Volume
79
Issue
4
Copyright Statement
©2019 The Author(s). Published by Elsevier Ltd on behalf of The British Infection Association. This is an
open access article under the CCBY-NC-ND license (https://creativecommons.org/licenses/by-nc-nd/4.0/)
open access article under the CCBY-NC-ND license (https://creativecommons.org/licenses/by-nc-nd/4.0/)
Identifier
https://www.sciencedirect.com/science/article/pii/S0163445319302403?via%3Dihub
Subjects
Science & Technology
Life Sciences & Biomedicine
Infectious Diseases
Bacteraemia
Staphylococcus aureus
Mortality
Recurrence
Rifampicin
RISK-FACTORS
RIFAMPICIN
MULTICENTER
IMPACT
Bacteraemia
Mortality
Recurrence
Rifampicin
Staphylococcus aureus
United Kingdom Clinical Infection Research Group (UKCIRG)
Microbiology
1103 Clinical Sciences
Publication Status
Published
Date Publish Online
2019-08-06