Adjunctive rifampicin does not improve outcomes in S. aureus bacteremia

Adjunctive rifampicin did not benefit patients with Staphylococcus aureus bacteremia, researchers in the United Kingdom reported.

“Opinions on best management vary widely, but current guidelines recommend S. aureus bacteremia be treated with at least 14 days of an intravenous beta-lactam antibiotic, or a glycopeptide if the bacteria are resistant to methicillin,” Guy E. Thwaites, FRCP, professor in the Nuffield Department of Medicine at the University of Oxford, and colleagues wrote. “Combination antibiotic therapy is generally not recommended, except in severe MRSA infections; however, evidence in support of its use in such cases is weak. Adjunctive rifampicin has long been hypothesized to improve outcomes for serious S. aureus infections.”

In the ARREST study, the researchers performed a randomized, double-blind controlled trial of adults from 29 U.K. hospitals with S. aureus bacteremia (n = 758). Thwaites and colleagues used a computer-generated list to randomly assign patients to either 2 weeks of adjunctive rifampicin (n = 370) or a placebo (n = 388) paired with standard antibiotic treatment. The main outcome was time to treatment failure or recurrence of disease.

Four hundred eighty-five patients (64%) had community-acquired S. aureus, 132 (17%) had nosocomial S. aureus infections and 47 (6%) had MRSA. Forty percent of patients (n = 301) had an initial deep infection focus. Patients received standard antibiotic therapy for 29 days, with most (82%) receiving flucloxacillin.

By week 12, 17% of patients in the rifampicin group (n = 62) experienced disease recurrence or treatment failure, or died, the researchers reported, compared with 18% in the placebo group. Thwaites and colleagues reported no differences in either serious (P = .17) or grade 3 to 4 (P = .36) adverse events between groups at 12 weeks. More patients in the rifampicin group (17%; n = 63) than the placebo group (10%; n = 39) experienced antibiotic or trial drug-modifying adverse events (P = .004). Similarly, more patients in the rifampicin group experienced drug interactions (n = 24; 6% vs. n = 6; 2%; P = .0005).

“Clinicians now have additional evidence to answer two S. aureus bacteremia antibiotic therapy questions: daptomycin is not inferior to standard antibiotic therapy, and adjunctive rifampicin does not improve outcomes,” Thomas L. Holland, MD, and Vance G. Fowler, Jr., MD, assistant professor and professor of Duke University School of Medicine, and colleagues wrote.

These remaining questions, Fowler and Holland added, included whether other combinations of antibiotics would improve outcomes, how much time is necessary for treating S. aureus bacteremia and whether oral stepdown therapy is ever appropriate for the condition.

“The challenge now is to build on the lessons of ARREST to inform the next generation of studies,” they wrote. “Our patients should not wait another decade to see the next big questions answered.” – by Andy Polhamus