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Low-Dose Acetylsalicylic Acid Treatment and Impact on Short-Term Mortality in Staphylococcus aureus Bloodstream Infection

A Propensity Score–Matched Cohort Study

Osthoff, Michael MD; Sidler, Jan A. MD; Lakatos, Botond MD; Frei, Reno MD; Dangel, Marc MPH; Weisser, Maja MD; Battegay, Manuel MD; Widmer, Andreas F. MD, MS

doi: 10.1097/CCM.0000000000001554
Clinical Investigations

Objectives: Staphylococcus aureus bloodstream infection is associated with considerable mortality. Experimental models suggest a direct antistaphylococcal effect of acetylsalicylic acid, but evidence from human studies is scarce. We aimed to estimate the effect of low-dose acetylsalicylic acid therapy on mortality in bloodstream infections caused by S. aureus compared with Escherichia coli.

Design: Retrospective cohort study based on observational data from 838 and 602 episodes of S. aureus and E. coli bloodstream infection, respectively.

Setting: Swiss tertiary referral center.

Patients: Adult patients with S. aureus and E. coli bloodstream infection, respectively, categorized according to low-dose acetylsalicylic acid therapy as outpatient or inpatient before bacteremia.

Interventions: None.

Measurements and Main Results: Thirty-day all-cause mortality was analyzed in a total of 314 propensity score–matched S. aureus bloodstream infection and in 268 E. coli bloodstream infection patients, respectively (1:1 match of low-dose acetylsalicylic acid users and nonusers). S. aureus bloodstream infection cases and controls were equally matched for relevant confounders except treatment with statins, which was strongly associated with a low-dose acetylsalicylic acid use (p < 0.001). At day 30, 12.1% of cases and 27.4% of controls had died (hazard ratio, 0.40; p < 0.001). Low-dose acetylsalicylic acid use was associated with a reduced 30-day all-cause mortality in multivariate analysis (hazard ratio, 0.38; 95% CI, 0.21–0.69; p = 0.001) of matched patients and also of the entire cohort (n = 689) after adjustment for the propensity score (hazard ratio, 0.58, 95% CI, 0.34–0.98; p = 0.04). In contrast, low-dose acetylsalicylic acid use was not associated with the primary endpoint in patients with E. coli bloodstream infection (hazard ratio, 0.78; 95% CI, 0.40–1.55; p = 0.8).

Conclusions: Low-dose acetylsalicylic acid at the time of bloodstream infection was strongly associated with a reduced short-term mortality in patients with S. aureus bloodstream infection. Future studies are required to investigate if early low-dose acetylsalicylic acid is a suitable treatment in patients with S. aureus bloodstream infection.

1Division of Infectious Diseases and Hospital Epidemiology, Departments of Medicine and Clinical Research, University Hospital Basel, Basel, Switzerland.

2Division of Clinical Microbiology, Departments of Medicine and Clinical Research, University Hospital Basel, Basel, Switzerland.

Drs. Osthoff and Sidler contributed equally to this study.

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This work was supported by the Division of Infectious Diseases and Hospital Epidemiology, University Hospital Basel, Basel, Switzerland.

Dr. Lakatos disclosed other support (Clinical Research Fellowship Program jointly supported by Swiss Society or Infectious Diseases and International Society for Infectious Diseases [payment is not related to the submitted work]). Dr. Frei disclosed other financial relationships with International Health Management Associates, Inc. (Schaumburg, IL, USA), Paul Ehrlich Gesellschaft, (Bonn, Germany), JMI Laboratories (North Liberty, IA, USA), Funginos (CHUV, Lausanne, Switzerland), bioMérieux (Geneva, Switzerland), Axon Lab AG (Baden, Switzerland), MSD (Luzern, Switzerland). All financial relationships indicated are related to other studies than the submitted paper/study. His institution received funding from the Swiss Tropical Institute (Basel, Switzerland), Hutman Diagnostics (Basel, Switzerland), and Roche Diagnostics (Baar, Switzerland). The remaining authors have disclosed that they do not have any potential conflicts of interest.

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