Erlin Institute of Health, 10117 Berlin, Germany; nora.renz@COX-2 drug 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: andrej.trampuz@charite.deAbstract: Rifampin is actually a potent antibiotic against staphylococcal implant-associated infections. Within the absence of implants, existing data suggest against the use of rifampin combinations. Within the past decades, abundant preclinical and clinical proof has accumulated supporting its role in biofilm-related infections.Within the present article, experimental data from animal models of foreignbody CDK4 web Infections and clinical trials are reviewed. The risk for emergence of rifampin resistance and multiple drug interactions are emphasized. A current randomized controlled trial (RCT) displaying no effective impact of rifampin in sufferers with acute staphylococcal periprosthetic joint infection treated with prosthesis retention is critically reviewed and information interpreted. Offered the current powerful proof demonstrating the benefit of rifampin, the conduction of an adequately powered RCT with acceptable definitions and interventions would likely not comply with ethical requirements. Search phrases: rifampin; biofilm; prosthetic joint infectionCitation: Renz, N.; Trampuz, A.; Zimmerli, W. Controversy concerning the Function of Rifampin in Biofilm Infections: Is It Justified Antibiotics 2021, 10, 165. antibiotics10020165 Academic Editor: Sigrun Eick Received: 17 January 2021 Accepted: 3 February 2021 Published: five February1. Introduction Rifampin is amongst the first-line drugs against tuberculosis. In addition, it has been applied against non-mycobacterial microorganisms, mostly staphylococci, for at least 50 years [1]. Nevertheless, its spot in extreme staphylococcal infections not involving an implanted device remained unclear for decades mainly because no systematic comparative studies had been performed. Inside the meantime, couple of studies have already been published on this subject. In 5 randomized controlled trials and two retrospective cohort research in sufferers with Staphylococcus aureus bacteremia, no difference of mortality may be shown [2]. A current multicenter, randomized, double-blind placebo-controlled trial confirmed these information in 758 patients [3]. In the study of Rieg et al. [4], only the subgroup of individuals with implants had significantly less late complications associated to S. aureus bacteremia when treated with combination therapy (4.5 vs. ten.6 , p = 0.03). Most of them were treated having a rifampin mixture regimen, suggesting a advantage of antibiofilm activity in comparison to therapy without the need of rifampin. In contrast, the addition of rifampin to regular therapy showed no advantage in individuals with native valve infective endocarditis brought on by S. aureus [5]. Thus, the latest data advocate against the uncritical use of rifampin combination therapy in patients with extreme staphylococcal infections in absence of implants. In contrast, the advantage of rifampin in sufferers with staphylococcal implant-associated infection is effectively documented primarily based on abundant in-vitro, animal, and clinical information, as summarized in a recent evaluation [6]. Until lately, only one particular randomized controlled trial (RCT) existed, in which the added worth of rifampin was shown in individuals with orthopedic implant-associated staphylococcal infections [7]. In 2020, a second RCT.