Adjunctive rifampicin may improve outcomes in Staphylococcus aureus bacteraemia: a systematic review

Staphylococcus aureus bacteraemia (SAB) is associated with substantial morbidity and mortality. By surviving within leukocytes, S. aureus can evade both immunological defences and antimicrobial drugs, thus facilitating haematogenous dissemination. We performed a systematic review to determine whether antimicrobials with intracellular activity improve outcomes in SAB when used as an adjunct to β-lactam or glycopeptide monotherapy. The Pubmed/MEDLINE, Embase and Cochrane databases were systematically searched for eligible studies that reported on the use of first-line antimicrobials plus a single additional antimicrobial of interest in patients with SAB (any cause). Six relevant studies were identified, all reporting on rifampicin use. Four studies (three randomized controlled trials and one cohort) reported on adults with SAB, including 54 patients treated with adjunctive rifampicin and 44 standard-therapy controls. Estimated across all of these studies, adjunctive rifampicin was associated with trends towards reduced all-cause mortality and reduced clinical or bacteriological failure. The fifth study indicated that adjunctive rifampicin accelerates the resolution of persistent SAB in neonates. Data from the sixth study were considered flawed owing to differences in co-morbidities between groups. Limited data suggest that rifampicin-induced hepatitis is not clinically significant but that drug interactions are. In conclusion, adjunctive rifampicin may improve outcomes in SAB when used as an adjunct to β-lactam or glycopeptide monotherapy.