Adjunctive rifampin not beneficial for Staph aureus bacteremia

Last Updated: 2017-12-28

By Will Boggs MD

NEW YORK (Reuters Health) - Adjunctive rifampin, also called rifampicin, provides no significant benefit over standard antibiotic therapy in patients with Staphylococcus aureus bacteremia, according to results from the ARREST trial.

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. The findings were published online December 14 in The Lancet.

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 conclude. "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."

Dr. Vance G. Fowler, Jr., from Duke University School of Medicine, Durham, North Carolina, who coauthored a related editorial, told Reuters Health by email, "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."

"The influence of these findings on the use of rifampin in this setting should be along the lines of the asteroid's influence on the dinosaurs at the end of the Cretaceous period," he concluded.

Dr. Fowler added, "Clinical trials in infectious diseases are hard, and clinical trials that test approved antibiotics to treat drug-resistant bacteria are darn near impossible. Our patients deserve clinical trials networks that identify, design, fund, and execute studies to confuse the issue with facts, and improve clinical care."

SOURCES: http://bit.ly/2kwsou0 and http://bit.ly/2pLccdY

Lancet 2017.