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      Staphylococcus epidermidis Biofilms Have a High Tolerance to Antibiotics in Periprosthetic Joint Infection

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          Abstract

          Both Staphylococcus aureus and Staphylococcus epidermidis are commonly associated with periprosthetic joint infections (PJIs). The treatment of PJI can be challenging because biofilms are assumed to have an increased intolerance to antibiotics. This makes the treatment of PJI challenging from a clinical perspective. Although S. aureus has been previously demonstrated to have increased biofilm antibiotic tolerance, this has not been well established with Staphylococcus epidermidis. A prospective registry of PJI S. epidermidis isolates was developed. The efficacy of clinically relevant antibiotics was quantified against these isolates. S. epidermidis planktonic minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were collected using clinical laboratory standard index (CLSI) assays for eight antibiotics (doxycycline, vancomycin, daptomycin, clindamycin, rifampin, nafcillin, and trimethoprim/sulfamethoxazole). Mature biofilms were grown in vitro, after which minimum biofilm inhibitory concentration (MBIC) and minimum biofilm bactericidal concentration (MBBC) were quantified. Only rifampin and doxycycline had a measurable MBIC across all tested isolates. Based on MBBC, 64% of S. epidermidis biofilms could be eliminated by rifampin, whereas only 18% by doxycycline. S. epidermidis biofilm was observed to have a high tolerance to antibiotics as compared to planktonic culture. Isolate biofilm antibiotic tolerance varied to a larger degree than was seen in planktonic cultures.

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          Most cited references31

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          Determination of minimum inhibitory concentrations.

          Minimum inhibitory concentrations (MICs) are defined as the lowest concentration of an antimicrobial that will inhibit the visible growth of a microorganism after overnight incubation, and minimum bactericidal concentrations (MBCs) as the lowest concentration of antimicrobial that will prevent the growth of an organism after subculture on to antibiotic-free media. MICs are used by diagnostic laboratories mainly to confirm resistance, but most often as a research tool to determine the in vitro activity of new antimicrobials, and data from such studies have been used to determine MIC breakpoints. MBC determinations are undertaken less frequently and their major use has been reserved for isolates from the blood of patients with endocarditis. Standardized methods for determining MICs and MBCs are described in this paper. Like all standardized procedures, the method must be adhered to and may not be adapted by the user. The method gives information on the storage of standard antibiotic powder, preparation of stock antibiotic solutions, media, preparation of inocula, incubation conditions, and reading and interpretation of results. Tables giving expected MIC ranges for control NCTC and ATCC strains are also supplied.
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            Definitions and guidelines for research on antibiotic persistence

            Increasing concerns about the rising rates of antibiotic therapy failure and advances in single-cell analyses have inspired a surge of research into antibiotic persistence. Bacterial persister cells represent a subpopulation of cells that can survive intensive antibiotic treatment without being resistant. Several approaches have emerged to define and measure persistence, and it is now time to agree on the basic definition of persistence and its relation to the other mechanisms by which bacteria survive exposure to bactericidal antibiotic treatments, such as antibiotic resistance, heteroresistance or tolerance. In this Consensus Statement, we provide definitions of persistence phenomena, distinguish between triggered and spontaneous persistence and provide a guide to measuring persistence. Antibiotic persistence is not only an interesting example of non-genetic single-cell heterogeneity, it may also have a role in the failure of antibiotic treatments. Therefore, it is our hope that the guidelines outlined in this article will pave the way for better characterization of antibiotic persistence and for understanding its relevance to clinical outcomes.
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              Diagnosis and management of prosthetic joint infection: clinical practice guidelines by the Infectious Diseases Society of America.

              These guidelines are intended for use by infectious disease specialists, orthopedists, and other healthcare professionals who care for patients with prosthetic joint infection (PJI). They include evidence-based and opinion-based recommendations for the diagnosis and management of patients with PJI treated with debridement and retention of the prosthesis, resection arthroplasty with or without subsequent staged reimplantation, 1-stage reimplantation, and amputation.
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                Author and article information

                Journal
                Life (Basel)
                Life (Basel)
                life
                Life
                MDPI
                2075-1729
                24 October 2020
                November 2020
                : 10
                : 11
                : 253
                Affiliations
                [1 ]Arthritis and Arthroplasty Design Group, Department of Orthopaedic Surgery, University of Pittsburgh, Pittsburgh, PA 15260, USA; j.koch@ 123456pitt.edu (J.A.K.); tmp5561@ 123456psu.edu (T.M.P.); alc272@ 123456pitt.edu (A.J.C.); jbm42@ 123456pitt.edu (J.B.M.); dom13@ 123456pitt.edu (D.M); kmb227@ 123456pitt.edu (K.M.B.)
                [2 ]Department of Infectious Diseases and Microbiology, University of Pittsburgh, Pittsburgh, PA 15260, USA
                [3 ]Division of Infectious Disease, Department of Internal Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA 15260, USA; shahnb@ 123456upmc.edu
                [4 ]The Bone and Joint Center, Magee Womens Hospital of the University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA
                [5 ]Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA 15260, USA
                [6 ]Clinical and Translational Science Institute, University of Pittsburgh, Pittsburgh, PA 15260, USA
                Author notes
                Author information
                https://orcid.org/0000-0001-5692-7970
                https://orcid.org/0000-0002-4511-1308
                Article
                life-10-00253
                10.3390/life10110253
                7693748
                33114423
                48eb5b7b-6472-4d0d-acbf-c0261c35e10c
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 09 October 2020
                : 20 October 2020
                Categories
                Communication

                periprosthetic joint infection,infection,antibiotic resistance,pji,s. epidermidis,arthroplasty

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