Erlin Institute of Overall health, 10117 Berlin, Germany; [email protected] Department of Infectious Ailments, 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 really a potent antibiotic against staphylococcal implant-associated infections. Inside the absence of implants, current data suggest against the use of rifampin combinations. Within the past decades, abundant preclinical and clinical proof has accumulated supporting its function in biofilm-related infections.Within the present article, experimental information from animal models of foreignbody infections and clinical trials are reviewed. The danger for emergence of rifampin resistance and numerous drug interactions are emphasized. A recent randomized controlled trial (RCT) displaying no helpful effect of rifampin in patients with acute staphylococcal periprosthetic joint infection treated with prosthesis retention is critically reviewed and information interpreted. Offered the current strong evidence demonstrating the advantage of rifampin, the conduction of an adequately powered RCT with suitable definitions and interventions would probably not comply with ethical standards. Search phrases: rifampin; biofilm; prosthetic joint infectionCitation: Renz, N.; Trampuz, A.; Zimmerli, W. Controversy concerning the Role of Rifampin in Biofilm Infections: Is It Caspase 1 list Justified Antibiotics 2021, 10, 165. https://doi.org/10.3390/ antibiotics10020165 Academic Editor: Sigrun Eick Received: 17 January 2021 Accepted: three February 2021 Published: five February1. Introduction Rifampin is amongst the first-line drugs against tuberculosis. Additionally, it has been made use of against non-mycobacterial microorganisms, mostly staphylococci, for no less than 50 years [1]. However, its place in serious staphylococcal infections not involving an implanted device remained unclear for decades for the reason that no systematic comparative research had been performed. In the meantime, few studies have already been published on this topic. In five randomized controlled trials and two retrospective cohort research in patients with Staphylococcus aureus bacteremia, no difference of mortality may very well be shown [2]. A recent multicenter, randomized, double-blind placebo-controlled trial confirmed these information in 758 individuals [3]. Within the study of Rieg et al. [4], only the subgroup of sufferers with implants had much less late complications related to S. aureus bacteremia when treated with combination therapy (four.5 vs. 10.six , p = 0.03). The majority of them had been treated having a rifampin mixture regimen, suggesting a benefit of antibiofilm activity compared to remedy without having rifampin. In contrast, the addition of rifampin to normal therapy showed no benefit in individuals with native valve infective endocarditis brought on by S. aureus [5]. As a result, the latest data BRDT Compound advocate against the uncritical use of rifampin mixture therapy in individuals with severe staphylococcal infections in absence of implants. In contrast, the advantage of rifampin in patients with staphylococcal implant-associated infection is well documented primarily based on abundant in-vitro, animal, and clinical data, as summarized inside a recent assessment [6]. Till lately, only a single randomized controlled trial (RCT) existed, in which the added worth of rifampin was shown in sufferers with orthopedic implant-associated staphylococcal infections [7]. In 2020, a second RCT.