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      Bacterial Etiology and Risk Factors Associated with Cellulitis and Purulent Skin Abscesses in Military Trainees

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          Abstract

          Military trainees are at high risk for skin and soft-tissue infections (SSTIs). Although Staphylococcus aureus is associated with purulent SSTI, it is unclear to what degree this pathogen causes nonpurulent cellulitis. To inform effective prevention strategies and to provide novel insights into SSTI pathogenesis, we aimed to determine the etiology of SSTI in this population. We conducted a prospective observational study in US Army Infantry trainees with SSTI (cutaneous abscesses and cellulitis) from July 2012 through December 2014. We used standard microbiology, serology, and high-throughput sequencing to determine the etiology of SSTI. Furthermore, we compared purported risk factors as well as anatomic site colonization for S. aureus. Among 201 SSTI cases evaluated for SSTI risk factors, cellulitis was associated with lower extremity blisters (P = 0.01) and abscess was associated with methicillin-resistant S. aureus (MRSA) colonization (P<0.001). Among the 22 tested cellulitis cases that were part of the microbiome analysis, only 1 leading edge aspirate was culturable (Coagulase-negative Staphylococcus). Microbiome evaluation of aspirate specimens demonstrated that Rhodanobacter terrae was the most abundant species (66.8% average abundance), while abscesses were dominated by S. aureus (92.9% average abundance). Although abscesses and cellulitis share the spectrum of clinical SSTI, the bacterial etiologies as determined by current technology appear distinct. Furthermore, the presence of atypical bacteria within cellulitis aspirates may indicate novel mechanisms of cellulitis pathogenesis.

          Clinical Trials Registration: NCT01105767.

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          Most cited references35

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          Methicillin-resistant S. aureus infections among patients in the emergency department.

          Methicillin-resistant Staphylococcus aureus (MRSA) is increasingly recognized in infections among persons in the community without established risk factors for MRSA. We enrolled adult patients with acute, purulent skin and soft-tissue infections presenting to 11 university-affiliated emergency departments during the month of August 2004. Cultures were obtained, and clinical information was collected. Available S. aureus isolates were characterized by antimicrobial-susceptibility testing, pulsed-field gel electrophoresis, and detection of toxin genes. On MRSA isolates, we performed typing of the staphylococcal cassette chromosome mec (SCCmec), the genetic element that carries the mecA gene encoding methicillin resistance. S. aureus was isolated from 320 of 422 patients with skin and soft-tissue infections (76 percent). The prevalence of MRSA was 59 percent overall and ranged from 15 to 74 percent. Pulsed-field type USA300 isolates accounted for 97 percent of MRSA isolates; 74 percent of these were a single strain (USA300-0114). SCCmec type IV and the Panton-Valentine leukocidin toxin gene were detected in 98 percent of MRSA isolates. Other toxin genes were detected rarely. Among the MRSA isolates, 95 percent were susceptible to clindamycin, 6 percent to erythromycin, 60 percent to fluoroquinolones, 100 percent to rifampin and trimethoprim-sulfamethoxazole, and 92 percent to tetracycline. Antibiotic therapy was not concordant with the results of susceptibility testing in 100 of 175 patients with MRSA infection who received antibiotics (57 percent). Among methicillin-susceptible S. aureus isolates, 31 percent were USA300 and 42 percent contained pvl genes. MRSA is the most common identifiable cause of skin and soft-tissue infections among patients presenting to emergency departments in 11 U.S. cities. When antimicrobial therapy is indicated for the treatment of skin and soft-tissue infections, clinicians should consider obtaining cultures and modifying empirical therapy to provide MRSA coverage. Copyright 2006 Massachusetts Medical Society.
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            Investigating deep phylogenetic relationships among cyanobacteria and plastids by small subunit rRNA sequence analysis.

            Small subunit rRNA sequence data were generated for 27 strains of cyanobacteria and incorporated into a phylogenetic analysis of 1,377 aligned sequence positions from a diverse sampling of 53 cyanobacteria and 10 photosynthetic plastids. Tree inference was carried out using a maximum likelihood method with correction for site-to-site variation in evolutionary rate. Confidence in the inferred phylogenetic relationships was determined by construction of a majority-rule consensus tree based on alternative topologies not considered to be statistically significantly different from the optimal tree. The results are in agreement with earlier studies in the assignment of individual taxa to specific sequence groups. Several relationships not previously noted among sequence groups are indicated, whereas other relationships previously supported are contradicted. All plastids cluster as a strongly supported monophyletic group arising near the root of the cyanobacterial line of descent.
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              Determinants of mortality for necrotizing soft-tissue infections.

              The authors determined the risk factors of mortality in patients with necrotizing soft-tissue infections (NSTIs) and examined the incidence and mortality from NSTI secondary to Streptococcus pyogenes. All patients with NSTIs who were treated between January 1989 and June 1994 were analyzed for presentation, etiology, factors important in pathogenesis and treatment, and mortality. Sixty-five patients were identified with NSTIs secondary to postoperative wound complications (18), trauma (15), cutaneous disease (15), idiopathic causes (10), perirectal abscesses (3), strangulated hernias (2), and subcutaneous injections (2). Necrotizing soft-tissue infections were polymicrobial in 45 patients (69%). S. pyogenes was isolated in only 17% of the NSTIs, but accounted for 53% of monomicrobial infections. Eight of ten idiopathic infections were caused by a single bacterium (p = 0.0005), whereas 82% of postoperative infections were polymicrobial. An average of 3.3 operative debridements per patient and amputation in 12 patients were necessary to control infection. The overall mortality was 29%; mortality from S. pyogenes infection was only 18%. The average time from admission to operation was 90 hours in nonsurvivors versus 25 hours in survivors (p = 0.0002). Other risk factors previously associated with the development of NSTIs did not affect mortality. Early debridement of NSTI was associated with a significant decrease in mortality. S. pyogenes infection was the most common cause of monomicrobial NSTI, but was not associated with an increased mortality.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                25 October 2016
                2016
                : 11
                : 10
                : e0165491
                Affiliations
                [1 ]Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, Maryland, United States of America
                [2 ]The University of Toledo Medical Center, Toledo, Ohio, United States of America
                [3 ]Infectious Disease Clinical Research Program, Department of Preventive Medicine and Biometrics, Uniformed Services University of the Health Sciences, Bethesda, Maryland, United States of America
                [4 ]Martin Army Community Hospital, Fort Benning, Georgia, United States of America
                [5 ]The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc, Bethesda, Maryland, United States of America
                [6 ]Biological Defense Research Directorate, Naval Medical Research Center, Frederick, Fort Detrick, Maryland, United States of America
                [7 ]Infectious Diseases Directorate, Wound Infections Department, Naval Medical Research Center, Silver Spring, Maryland, United States of America
                [8 ]Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland, United States of America
                Purdue University, UNITED STATES
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                • Conceptualization: RCJ MWE CDS EVM JBL NT DKB ERH DSM.

                • Formal analysis: RCJ DM EME TC.

                • Funding acquisition: MWE ERH DSM.

                • Investigation: RCJ PTL DM EME CLR TC.

                • Methodology: RCJ MWE CDS EVM NT DKB ERH DSM.

                • Project administration: MWE CDS EVM JBL DKB ERH DSM.

                • Resources: MWE CDS EVM CLR KAB.

                • Supervision: MWE NT DKB ERH KAB DSM.

                • Visualization: RCJ.

                • Writing – original draft: RCJ MWE PTL DSM.

                • Writing – review & editing: RCJ MWE CDS EVM PTL DM EME JBL CLR TC NT DKB ERH KAB DSM.

                Author information
                http://orcid.org/0000-0002-2114-2951
                Article
                PONE-D-16-30611
                10.1371/journal.pone.0165491
                5079656
                27780238
                f7cc4bec-a5ac-41ad-9344-595eb18bd41e

                This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

                History
                : 31 July 2016
                : 12 October 2016
                Page count
                Figures: 1, Tables: 4, Pages: 16
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/100000005, U.S. Department of Defense;
                Award ID: HT9404-12-1-0019
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/100000005, U.S. Department of Defense;
                Award ID: GEIS:HU0001-10-1-0018
                Award Recipient :
                Funded by: Military Infectious Diseases Research Program
                Award ID: HT9404-12-1-0012
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/100000060, National Institute of Allergy and Infectious Diseases;
                Award ID: YI-AI-5072
                Primary support for this work was provided by a US Department of Defense Program Project Grant (HT9404-12-1-0019 to DSM, MWE, and ERH). Additional support for this work was provided by the Department of Defense Global Emerging Infections Surveillance and Response System (GEIS;HU0001-10-1-0018 to MWE) and the Military Infectious Diseases Research Program (MIDRP; HT9404-12-1-0012 to M.W.E). The protocol was executed by the Infectious Disease Clinical Research Program (IDCRP), a Department of Defense (DoD) program executed through the Uniformed Services University of the Health Sciences, and funded in part by the National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), under Inter-Agency Agreement [Y1-AI-5072]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Medicine and Health Sciences
                Infectious Diseases
                Bacterial Diseases
                Cellulitis
                Medicine and Health Sciences
                Diagnostic Medicine
                Signs and Symptoms
                Abscesses
                Medicine and Health Sciences
                Pathology and Laboratory Medicine
                Signs and Symptoms
                Abscesses
                Biology and life sciences
                Organisms
                Bacteria
                Staphylococcus
                Staphylococcus aureus
                Methicillin-resistant Staphylococcus aureus
                Biology and life sciences
                Microbiology
                Medical microbiology
                Microbial pathogens
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                Staphylococcus
                Staphylococcus aureus
                Methicillin-resistant Staphylococcus aureus
                Medicine and health sciences
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                Pathogens
                Microbial pathogens
                Bacterial pathogens
                Staphylococcus
                Staphylococcus aureus
                Methicillin-resistant Staphylococcus aureus
                Biology and Life Sciences
                Organisms
                Bacteria
                Staphylococcus
                Staphylococcus Aureus
                Biology and Life Sciences
                Microbiology
                Medical Microbiology
                Microbial Pathogens
                Bacterial Pathogens
                Staphylococcus
                Staphylococcus Aureus
                Medicine and Health Sciences
                Pathology and Laboratory Medicine
                Pathogens
                Microbial Pathogens
                Bacterial Pathogens
                Staphylococcus
                Staphylococcus Aureus
                Biology and Life Sciences
                Microbiology
                Medical Microbiology
                Microbiome
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                Genetics
                Genomics
                Microbial Genomics
                Microbiome
                Biology and Life Sciences
                Microbiology
                Microbial Genomics
                Microbiome
                Medicine and Health Sciences
                Dermatology
                Skin Infections
                Medicine and Health Sciences
                Infectious Diseases
                Skin Infections
                Biology and Life Sciences
                Molecular Biology
                Molecular Biology Techniques
                Cloning
                Research and Analysis Methods
                Molecular Biology Techniques
                Cloning
                Medicine and Health Sciences
                Pathology and Laboratory Medicine
                Etiology
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