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Background: Staphylococcus aureus (S. aureus) bacteremia (SAB) has high morbidity and mortality, with the development of methicillin-resistant S. aureus (MRSA) and the recognized shortcomings of vancomycin, its management is becoming more complicated. Considering the capability to penetrate cells, tissues and biofilms, rifampin has been used as adjunctive agent to against staphylococcal activity. Objectives: We performed this meta-analysis, aimed to explore the efficacy of adjunctive rifampin for the treatment of SAB. Methods: Medical literatures were searched in the Pubmed, Medline, Embase and Cochrane databases up to October 2018. Patients with SAB received treatment with or without rifampin were included. The risk ratio (RR) and 95% confidence intervals (CI) of mortality, rate of bacteriological failure and relapse were estimated. Results: Seven articles (five randomized controlled trials and two retrospective cohort studies) enrolling 979 and 636 patients of SAB treated with and without rifampin, respectively, were included. There was no difference of mortality between the adjunctive rifampin therapy and standard therapy on SAB (RR: 0.771, 95% CI: 0.442 to 1.347, I2 = 70.4%). In the subgroup analyses, the decreased mortality was observed in the adjunctive rifampin treatment for patients without MRSA infection (RR: 0.509, 95% CI: 0.372 to 0.697, I2 = 8.8%). In addition, there was no difference of the rate of bacteriologic failure (RR: 0.602, 95% CI: 0.198 to 1.825, I2 = 0.0%) or relapse (RR: 0.574, 95% CI: 0.106 to 3.112, I2 = 77.9%) between the adjunctive rifampin therapy and standard therapy on SAB. Conclusions: In general, insufficient evidence supported the efficacy of adjunctive use of rifampin for treatment of SAB, adding rifampin to standard therapy didn't decrease the incidence of death, rate of bacteriologic failure and relapse. [ABSTRACT FROM AUTHOR]