Erlin Institute of Health, 10117 Berlin, Germany; [email protected] Department of Infectious Diseases, Bern University Hospital, University of Bern, 3010 Bern, Switzerland Interdisciplinary Unit of Orthopaedic Infections, Kantonsspital Baselland, 4410 Liestal, Switzerland; [email protected] Correspondence: [email protected]: Rifampin is often a potent antibiotic against staphylococcal implant-associated infections. Inside the absence of implants, existing data recommend against the usage of rifampin combinations. Inside the past decades, abundant preclinical and clinical evidence has accumulated supporting its part in biofilm-related infections.Within the present report, experimental information from animal models of foreignbody infections and clinical trials are reviewed. The risk for emergence of rifampin resistance and various drug interactions are emphasized. A current ALK3 Species randomized controlled trial (RCT) showing no effective impact of rifampin in patients with acute staphylococcal periprosthetic joint infection GLUT2 drug treated with prosthesis retention is critically reviewed and data interpreted. Provided the existing sturdy proof demonstrating the benefit of rifampin, the conduction of an adequately powered RCT with proper definitions and interventions would possibly not comply with ethical standards. Search phrases: rifampin; biofilm; prosthetic joint infectionCitation: Renz, N.; Trampuz, A.; Zimmerli, W. Controversy about the Part of Rifampin in Biofilm Infections: Is It Justified Antibiotics 2021, ten, 165. https://doi.org/10.3390/ antibiotics10020165 Academic Editor: Sigrun Eick Received: 17 January 2021 Accepted: 3 February 2021 Published: five February1. Introduction Rifampin is one of the first-line drugs against tuberculosis. Also, it has been utilized against non-mycobacterial microorganisms, mainly staphylococci, for at the least 50 years . However, its location in serious staphylococcal infections not involving an implanted device remained unclear for decades since no systematic comparative research had been performed. Inside the meantime, few research happen to be published on this subject. In 5 randomized controlled trials and two retrospective cohort research in individuals with Staphylococcus aureus bacteremia, no difference of mortality could be shown . A recent multicenter, randomized, double-blind placebo-controlled trial confirmed these information in 758 sufferers . Within the study of Rieg et al. , only the subgroup of patients with implants had much less late complications associated to S. aureus bacteremia when treated with combination therapy (4.five vs. ten.6 , p = 0.03). The majority of them have been treated using a rifampin combination regimen, suggesting a benefit of antibiofilm activity in comparison to treatment devoid of rifampin. In contrast, the addition of rifampin to typical therapy showed no benefit in individuals with native valve infective endocarditis caused by S. aureus . Thus, the most recent data advocate against the uncritical use of rifampin combination therapy in individuals with serious staphylococcal infections in absence of implants. In contrast, the benefit of rifampin in individuals with staphylococcal implant-associated infection is properly documented primarily based on abundant in-vitro, animal, and clinical data, as summarized inside a current evaluation . Till lately, only one particular randomized controlled trial (RCT) existed, in which the added value of rifampin was shown in individuals with orthopedic implant-associated staphylococcal infections . In 2020, a second RCT.