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      Removal of Staphylococcus aureus from skin using a combination antibiofilm approach

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          Abstract

          Staphylococcus aureus ( S. aureus) including methicillin resistant S. aureus (MRSA) is one of the primary microorganisms responsible for surgical site infection (SSI). Since S. aureus contamination is known to originate from the skin, eradicating it on the skin surface at surgical sites is an important intervention to reduce the chance of SSIs. Here we developed and evaluated the efficacy of a combination probiotic/brush sonication strategy for skin preparation at surgical, injection and insertion sites in medicine. A 24 h biofilm on porcine skin explants was used as a worst-case scenario for the evaluation of preparation strategies. Conventional ethanol wipes achieved 0.8~2 log reduction in viable bacteria depending on how many times wiped (x4 or x6). Brush sonication or probiotic supernatant pre-treatment alone achieved a similar reduction as ethanol wipes (1.4 and 0.7~1.4 log reduction, respectively). Notably, combining sonication and probiotic pre-treatment achieved a 4 log reduction in viable bacteria. In addition, probiotic supernatant incubation times as short as 2 h achieved the full effect of this reduction in the combined strategy. These findings suggest the promising potential of combination-format skin preparation strategies that can be developed to more effectively penetrate cracks and folds in the skin to remove biofilms.

          Skin cleaning: sonication and probiotics can beat biofilms

          Combining brush sonication with secretions from probiotic bacteria cleans skin before surgery more effectively than ethanol wipes. Researchers in the USA, led by K. Scott Phillips at the United States Food and Drug Administration, investigated removal of Staphylococcus aureus biofilm from pig skin as a “worst case” pre-surgical scenario. This bacterium is a major cause of serious and drug-resistant surgical site infections. Brush sonication or treatment with probiotic-derived solutions were individually approximately as effective as ethanol wipes, but in combination they proved substantially more effective. The treatment with the secretions surrounding probiotic bacterial cells requires exposure for several hours, but this could be readily achieved using a pre-surgery ointment. The sonication and probiotic combination could be developed into a highly effective pre-surgical procedure, penetrating cracks and folds in the skin to remove dangerous biofilms.

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          Most cited references41

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          Guideline for prevention of surgical site infection, 1999. Hospital Infection Control Practices Advisory Committee.

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            A Systematic Review of Risk Factors Associated with Surgical Site Infections among Surgical Patients

            Importance Surgical site infection (SSI) complicates 2-5% of surgeries in the United States. Severity of SSI ranges from superficial skin infection to life-threatening conditions such as severe sepsis, and SSIs are responsible for increased morbidity, mortality, and economic burden associated with surgery. Staphylococcus aureus (S. aureus) is a commonly-isolated organism for SSI, and methicillin-resistant S. aureus SSI incidence is increasing globally. Objective The objective of this systematic review was to characterize risk factors for SSI within observational studies describing incidence of SSI in a real-world setting. Evidence Review An initial search identified 328 titles published in 2002-2012; 57 were identified as relevant for data extraction. Extracted information included study design and methodology, reported cumulative incidence and post-surgical time until onset of SSI, and odds ratios and associated variability for all factors considered in univariate and/or multivariable analyses. Findings Median SSI incidence was 3.7%, ranging from 0.1% to 50.4%. Incidence of overall SSI and S. aureus SSI were both highest in tumor-related and transplant surgeries. Median time until SSI onset was 17.0 days, with longer time-to-onset for orthopedic and transplant surgeries. Risk factors consistently identified as associated with SSI included co-morbidities, advanced age, risk indices, patient frailty, and surgery complexity. Thirteen studies considered diabetes as a risk factor in multivariable analysis; 85% found a significant association with SSI, with odds ratios ranging from 1.5-24.3. Longer surgeries were associated with increased SSI risk, with a median odds ratio of 2.3 across 11 studies reporting significant results. Conclusions and Relevance In a broad review of published literature, risk factors for SSI were characterized as describing reduced fitness, patient frailty, surgery duration, and complexity. Recognition of risk factors frequently associated with SSI allows for identification of such patients with the greatest need for optimal preventive measures to be identified and pre-treatment prior to surgery.
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              agr-Dependent interactions of Staphylococcus aureus USA300 with human polymorphonuclear neutrophils.

              The emergence of serious infections due to community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) has fueled interest in the contributions of specific staphylococcal virulence factors to clinical disease. To assess the contributions of agr-dependent factors to the fate of organisms in polymorphonuclear neutrophils (PMN), we examined the consequences for organism and host cells of feeding PMN with wild-type CA-MRSA (LAC) or CA-MRSA (LAC agr KO) at different multiplicities of infection (MOIs). Phagocytosed organisms rapidly increased the transcription of RNAIII in a time- and MOI-dependent fashion; extracellular USA300 (LAC) did not increase RNAIII expression despite having the capacity to respond to autoinducing peptide-enriched culture medium. HOCl-mediated damage and intracellular survival were the same in the wild-type and USA300 (LAC agr KO). PMN lysis by ingested USA300 (LAC) was time- and MOI-dependent and, at MOIs >1, required α-hemolysin (hla) as USA300 (LAC agr KO) and USA300 (LAC hla KO) promoted PMN lysis only at high MOIs. Taken together, these data demonstrate activation of the agr operon in human PMN with the subsequent production of α-hemolysin and PMN lysis. The extent to which these events in the phagosomes of human PMN contribute to the increased morbidity and mortality of infections with USA300 (LAC) merits further study. Copyright © 2010 S. Karger AG, Basel.
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                Author and article information

                Contributors
                kenneth.phillips@fda.hhs.gov
                Journal
                NPJ Biofilms Microbiomes
                NPJ Biofilms Microbiomes
                NPJ Biofilms and Microbiomes
                Nature Publishing Group UK (London )
                2055-5008
                6 August 2018
                6 August 2018
                2018
                : 4
                : 16
                Affiliations
                [1 ]ISNI 0000 0001 2243 3366, GRID grid.417587.8, United States Food and Drug Administration, Office of Medical Products and Tobacco, Center for Devices and Radiological Health, Office of Science and Engineering Laboratories, Division of Biology, Chemistry and Materials Science, ; 10903 New Hampshire Ave, Silver Spring, MD 20993 USA
                [2 ]ISNI 0000000086837370, GRID grid.214458.e, Department of Environmental Health Sciences, School of Public Health, , University of Michigan, ; 6631 SPH Tower, 1415 Washington Heights, Ann Arbor, MI 48109 USA
                Author information
                http://orcid.org/0000-0002-6552-0694
                Article
                60
                10.1038/s41522-018-0060-7
                6079078
                30155267
                15c30e6e-3f52-448b-ba40-83114a52bd98
                © The Author(s) 2018

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 16 October 2017
                : 14 May 2018
                : 23 May 2018
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