Erlin Institute of Well being, 10117 Berlin, Germany; [email protected] Division 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 a potent antibiotic against staphylococcal implant-associated infections. Within the absence of implants, current data suggest against the usage of rifampin combinations. In the previous decades, abundant preclinical and clinical proof has accumulated supporting its function in biofilm-related infections.In the present write-up, experimental data from animal models of foreignbody infections and clinical trials are reviewed. The risk for emergence of rifampin resistance and several drug interactions are emphasized. A current randomized controlled trial (RCT) showing no advantageous effect of rifampin in patients with acute staphylococcal periprosthetic joint infection treated with prosthesis retention is critically reviewed and information interpreted. Provided the current robust proof demonstrating the benefit of rifampin, the conduction of an adequately powered RCT with acceptable definitions and interventions would most likely not comply with ethical requirements. Key phrases: rifampin; biofilm; prosthetic joint infectionCitation: Renz, N.; Trampuz, A.; Zimmerli, W. Controversy about the Role of Rifampin in JAK3 custom synthesis Biofilm Infections: Is It Justified Antibiotics 2021, 10, 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 among the first-line drugs against tuberculosis. Moreover, it has been made use of against non-mycobacterial microorganisms, mostly staphylococci, for at least 50 years [1]. Nonetheless, its location in extreme staphylococcal infections not Caspase 3 Purity & Documentation involving an implanted device remained unclear for decades mainly because no systematic comparative research had been performed. Within the meantime, few research have already been published on this subject. In 5 randomized controlled trials and two retrospective cohort studies in patients 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 individuals [3]. Within the study of Rieg et al. [4], only the subgroup of patients with implants had less late complications related to S. aureus bacteremia when treated with mixture therapy (4.5 vs. 10.six , p = 0.03). The majority of them had been treated using a rifampin combination regimen, suggesting a benefit of antibiofilm activity in comparison with therapy without having rifampin. In contrast, the addition of rifampin to typical therapy showed no benefit in individuals with native valve infective endocarditis triggered by S. aureus [5]. As a result, the most recent information advocate against the uncritical use of rifampin combination therapy in patients with serious staphylococcal infections in absence of implants. In contrast, the benefit of rifampin in patients with staphylococcal implant-associated infection is effectively documented based on abundant in-vitro, animal, and clinical information, as summarized in a recent critique [6]. Till lately, only 1 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.