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金黄色葡萄球菌菌血症复发、早期治疗失败和死亡的预测因素:ARREST 试验中的观察性分析。

Predictors of recurrence, early treatment failure and death from Staphylococcus aureus bacteraemia: Observational analyses within the ARREST trial.

机构信息

Medical Research Council Clinical Trials Unit at University College London, University College London, UK.

Guy's and St. Thomas' NHS Foundation Trust, London, UK; Kings College London, London, UK.

出版信息

J Infect. 2019 Oct;79(4):332-340. doi: 10.1016/j.jinf.2019.08.001. Epub 2019 Aug 6.

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 (p = 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.

摘要

目的

在金黄色葡萄球菌菌血症的 ARREST 试验中,辅助利福平并没有降低失败/复发/死亡的复合终点,但确实减少了复发。我们研究了临床定义的 14 天治疗失败、复发和金黄色葡萄球菌归因/非归因死亡率,并在 12 周时进行了进一步研究,以进一步确定其预测因素。

方法

使用竞争风险模型进行了事后探索性分析,以确定可能从利福平中获益的亚组。开发了基于点的复发风险评分,并用于比较利福平的益处。

结果

复发与肝肾功能衰竭、糖尿病和免疫抑制药物密切相关(p<0.005);相比之下,失败和金黄色葡萄球菌归因死亡率与年龄较大和中性粒细胞计数较高有关。更高的 SOFA 评分预测死亡率;更高的 Charlson 评分和深部初始感染病灶预测失败。出乎意料的是,在安慰剂(p=0.04)而不是利福平(p=0.60)参与者中,BMI 与复发风险增加相关(p=0.06)。在安慰剂(p=0.04)但不是利福平(p=0.60)参与者中,BMI 与复发风险增加相关(p=0.06)。在安慰剂(p=0.04)但不是利福平(p=0.60)参与者中,BMI 与复发风险增加相关(p=0.06)。在安慰剂(p=0.04)但不是利福平(p=0.60)参与者中,BMI 与复发风险增加相关(p=0.06)。在 23 名(74%)患者中,持续存在的病灶被判断为复发的主要原因。基于 BMI、免疫抑制、肾脏疾病、糖尿病、肝脏疾病的 5 因素风险评分(BIRDL)强烈预测复发(p<0.001)。

结论

利福平总体上减少了复发;使用简单的风险评分确定了具有最大绝对风险降低的患者。来源控制和足够的抗生素治疗时间仍然是预防复发和改善结果的关键。

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