Controversy about the Role of Rifampin in Biofilm Infections: Is It Justified?

Nora Renz,Werner Zimmerli,Andrej Trampuz

doi:10.3390/antibiotics10020165

Abstract

Rifampin is a potent antibiotic against staphylococcal implant-associated infections. In the absence of implants, current data suggest against the use of rifampin combinations. In the past decades, abundant preclinical and clinical evidence has accumulated supporting its role in biofilm-related infections.In the present article, experimental data from animal models of foreign-body infections and clinical trials are reviewed. The risk for emergence of rifampin resistance and multiple drug interactions are emphasized. A recent randomized controlled trial (RCT) showing no beneficial effect of rifampin in patients with acute staphylococcal periprosthetic joint infection treated with prosthesis retention is critically reviewed and data interpreted. Given the existing strong evidence demonstrating the benefit of rifampin, the conduction of an adequately powered RCT with appropriate definitions and interventions would probably not comply with ethical standards.

Highlights

Rifampin is one of the first-line drugs against tuberculosis
Most of them were treated with a rifampin combination regimen, suggesting a benefit of antibiofilm activity compared to treatment without rifampin
In 2020, a second randomized controlled trial (RCT) in patients with periprosthetic joint infection (PJI) was published, using different combination therapy regimens, which did not show a better outcome with addition of rifampin to standard treatment [8]

Summary

Introduction

Rifampin is one of the first-line drugs against tuberculosis. In addition, it has been used against non-mycobacterial microorganisms, mainly staphylococci, for at least 50 years [1]. In 2020, a second RCT in patients with periprosthetic joint infection (PJI) was published, using different combination therapy regimens, which did not show a better outcome with addition of rifampin to standard treatment [8] These unexpected data may unsettle clinicians with limited experience in the field of implant-associated infections. Based on our observation that rifampin could prevent, and cure experimental staphylococcal implant-associated infections [15], we performed additional animal experiments with rifampin combination therapy [16], followed by observational studies and one randomized controlled trial in patients with orthopedic implant-associated infections [7,17,18,19]. Data from randomized controlled trials are still not available in patients with non-orthopedic implant-associated infections

Evidence for the Efficacy of Rifampin in Animal Studies

Findings

Conclusions