A new study published in The Lancet suggest that adjunctive rifampin, also called rifampicin, provides no significant benefit over standard antibiotic therapy in patients with Staphylococcus aureus bacteremia.
Rifampin has long been used in the adjunctive treatment of S. aureus bacteremia, but the evidence supporting this use is weak, and the drug is associated with hepatic toxicity and substantial interactions with other medications.
Dr. Guy E. Thwaites, from the University of Oxford, and colleagues at 29 UK hospitals investigated whether adjunctive rifampin reduces the risk for treatment failure, recurrence, or death in a randomized, placebo-controlled trial involving 758 patients with confirmed S. aureus bacteremia.
In this ARREST trial, various active antibiotics were used, with most patients receiving flucloxacillin (82%) and half receiving vancomycin or teicoplanin at some point in the primary treatment course.
By week 12, the rifampin and placebo groups did not differ significantly in the combined endpoint of bacteriologically confirmed treatment failure or disease recurrence or death (17% vs. 18%, respectively). When the endpoint was clinically defined, the rates still did not differ between the rifampin (21%) and placebo (22%) groups.
Disease recurrences were less common with rifampin (1%) than with placebo (4%) in an exploratory post hoc analysis. Results persisted across a variety of subgroups, suggesting no heterogeneity in the absence of effect of rifampin.
During the 12-week study, 27% of the rifampin group and 24% of the placebo group experienced severe adverse events (P=0.17). Gastrointestinal disorders and renal or urinary disorders were more common with rifampin than with placebo, and there was a trend toward more renal grade 3-4 adverse events with rifampin (5%) than with placebo (2%).
“Adjunctive rifampicin did not improve outcomes from S. aureus bacteremia, with the exception of a modest reduction in disease recurrence,” the researchers said. “Given rifampicin had no effect on short-term or long-term mortality, substantially complicated other drug treatment, and widespread use risks increasing resistance among S. aureus and other bacteria (e.g., Mycobacterium tuberculosis), we consider that adjunctive rifampicin provides no overall benefit over standard antibiotic therapy in adults with S. aureus bacteremia.”
"It’s important to replace dogma with data in patient care, and ARREST did just that. As an adjunct therapy for patients with Staphylococcus aureus bacteremia and native valve endocarditis, rifampin doesn’t help, and may even harm,” said co-author Dr. Vance G. Fowler, Jr., from Duke University School of Medicine, Durham.