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Skin and Soft Tissue Infections

The overarching goal of the skin and soft tissue infections (SSTI) Research Area is to identify effective strategies for the prevention and control of SSTI, a major cause of morbidity among congregate military personnel in deployment and training settings.  Outbreaks of SSTI in military populations interrupt training cycles, compromise operational readiness, and impose a significant health care burden.  To date, hygiene-based SSTI prevention strategies have had limited effectiveness.  An effective vaccine for S. aureus, the predominant cause of SSTI, remains elusive.  Current research efforts aim to describe the clinical characteristics and natural history of SSTIs in military populations and to address knowledge gaps in the epidemiology, microbiology, and immunology of these infections.  

Research Area Description 

Skin and soft-tissue infections (SSTIs), most commonly caused by Staphylococcus aureus, are a common occurrence among military personnel, particularly trainees, resulting in a significant operational and healthcare burden.

Staphylococcus aureus, including methicillin-resistant S. aureus (MRSA), is well-recognized as a major contributor of SSTIs.  As personal hygiene-based measures have only a limited effectiveness and an effective S. aureus vaccine has not yet been identified, the primary objective of this research area is to identify effective strategies for the prevention and control of SSTIs among military populations. 

During the past year, the SSTI Cohort Study at Fort Benning completed enrollment and follow-up specimen/data collection in over 600 U.S. Army Infantry trainees.  The focus of the study was not only on the evaluation of the natural history, clinical characteristics, and risk factors of SSTIs, but also on the transmission of S. aureus in this setting.   Preliminary findings indicate that the trainees experience an intense and prolonged exposure to S. aureus over the course of the training cycle, with colonization of different anatomic sites by multiple strains of S. aureus being a common occurrence. Enrollment and follow-up specimen/data collection were also completed for the Submarine MRSA Study, which evaluated the prevalence of S. aureus colonization and incidence of SSTIs in the submariner population at Kings Bay, GA.    In addition, analysis of data collected through a case-control study conducted at Fort Benning (Epidemiology, Etiology, and Immunology of SSTI) is underway.  Findings from these detailed observational studies (all led by LTC Jason Bennett at USU) will expand the knowledge base of SSTI epidemiology, clinical characteristics, and risk factors, as well as provide further information on the epidemiology of S. aureus colonization and infection with inclusion of advanced immunology, microbiome, and microbial genetic analyses. 

Building on the foundation of these observational studies, the research area was awarded funding by the U.S. Army Medical Materiel Development Activity in 2017 for a phase 2a trial of a S. aureus vaccine candidate (NDV-3A; NovaDigm Therapeutics, LLC) to study the safety, immunogenicity, and efficacy of vaccination against nasal acquisition of S. aureus among trainees at Fort Benning.  This vaccine candidate has shown great promise for S. aureus prevention through a series of preclinical and clinical studies leading up to this proof of concept field trial.  Conducting a vaccine trial in a high-risk population of U.S. Army Infantry trainees represents a major advance in strategies related to the prevention of a common cause of infectious disease morbidity in military populations.

One reason for the success of this research area is the effective collaborations with various military laboratories, including Wound Infections Department at the Naval Medical Research Center (NMRC), Department of Microbiology and Immunology at the Uniformed Services University, and Biological Defense Research Directorate at NMRC.  In addition, due to the growing interest in whole genome sequencing of S. aureus and MRSA, collaborations with the Walter Reed Army Institute of Research and Harvard University have been established to evaluate genomics and proteomics of S. aureus transmission and SSTIs.  A new collaboration with New York University to study the immunology of S. aureus infections was also initiated.

In 2018, processing of immunology and microbiome specimens collected from the cohort studies will be completed.  Furthermore, genomic and proteomic characterization of S. aureus clinical and colonization isolates is also planned.  

Key Studies

IDCRP-001: Chlorhexidine Impregnated Cloths to Prevent Skin and Soft Tissue Infections in Marine Officer Candidates: A Randomized, Double-Blind, Placebo-Controlled Trial

IDCRP-035:  Evaluate the safety and immunogenicity of Staphylococcus aureus toxoid (rAT and rLuKS-PVL)

IDCRP-055: Evaluating strategies to prevent methicillin-resistant Staphylococcus aureus skin and soft tissue infections in military trainees at Fort Benning, Georgia

IDCRP-066: The disease and cost burden of SSTIs and MRSA-associated SSTIs in the U.S. Army Active Duty Training Population

IDCRP-068: Evaluation of the Prevalence of Staphylococcus aureus Colonization and Risk Factors for Infection among Naval Personnel in a Deployment Setting: a pilot study

IDCRP-074: Skin and soft-tissue infection in military trainees: epidemiology and economic burden of disease

IDCRP-090: Natural history of Staphylococcus aureus colonization, infection, and immune response in military trainees

Military Impact

Substantial operational, healthcare, and economic costs are associated with the burden of SSTI in military populations.  Efforts under this research area support the development of preventive efforts by (1) generating epidemiological, clinical, immunological, microbiological, and genomic data related to SSTIs associated with S. aureus and other etiologic agents; (2) detailing the epidemiological and economic burden of SSTI in military training setting; (3) assessing the effectiveness of personal hygiene-based efforts  on other common communicable diseases, such as acute respiratory infections; (4) examining transmission dynamics of MRSA in SSTI clusters among trainees; and (5) securing funding to conduct S. aureus vaccine trial among military trainees.

Highlights / Key Findings

  • Results from an observational, longitudinal study of S. aureus colonization and SSTI among 600 Infantry trainees revealed a 10% attack rate for SSTI and high rates of S. aureus and MRSA acquisition at multiple body sites
  • Genomic characterization of MRSA from clusters of SSTI among trainees  found patterns of both inter- and intra-class transmission,  suggesting that an environmental reservoir may contribute to persistence of MRSA in the training setting
  • Novel pathogens, such as Rhodanobacter spp., were frequently identified from cases of non-purulent cellulitis, while abscesses are typically associated with S. aureus
  • Awarded funding for a Phase 2 trial of a S. aureus  vaccine candidate among infantry trainees at Fort Benning to be executed in 2018

Partners and Collaborators

IDCRP efforts in the field of SSTI have addressed numerous aspects of SSTI, especially MRSA SSTI, ranging from epidemiology to prevention studies. These research efforts have led to collaborations with Centers for Disease Control and Prevention (CDC), National Institutes of Health (NIH), the Global Emerging Infections Surveillance (GEIS), Nabi Biopharmaceuticals, Naval Medical Research Center (NMRC), USUHS (Microbiology), Fort Benning (Martin Army Community Hospital), and on submarines.

Publications 2017

Millar EV, Rice GK, Elassal EM, et al. Genomic Characterization of USA300 MRSA to Evaluate Intraclass Transmission and Recurrence of SSTI among High Risk Military Trainees. Clinical Infectious Diseases. 2017;65(3):461-468.

Johnson RC, Ellis MW, Schlett CD, et al. Bacterial Etiology and Risk Factors Associated with Cellulitis and Purulent Skin Abscesses in Military Trainees. PLoS One. 2016 Oct 25;11(10):e0165491.

Singh J, Johnson RC, Schlett CD, et al. Multi-Body-Site Microbiome and Culture Profiling of Military Trainees Suffering from Skin and Soft Tissue Infections at Fort Benning, Georgia. mSphere. 2016 Oct 5;1(5):e00232.

Presentations 2017 

Military Health System Research Symposium, August 27-30, Kissimmee, FL

Oral Presentation: Millar EV, Rice GK, Elassal EM, Schlett CD, Bennett JW, Redden CL, Mor D, Law NN, Tribble DR, Hamilton T, Ellis MW, Bishop-Lilly KA. Genomic Characterization of USA300 MRSA to Evaluate Intraclass Transmission and Recurrence of SSTI among High Risk Military Trainees.

ID Week, October 3-7, San Diego, CA

Poster #265:  Schlett CD, Millar EV, Elassal EM, Law NN, Lyles DT, Hadley A, Dowlen S, Hardge D, Ellis MW, Bennett JW. Dynamics of S. aureus acquisition and colonization in a military training environment.

Publications 2014

Ellis MW, Schlett CD, Millar EV, et al. Prevalence of nasal colonization and strain concordance in patients with community-associated Staphylococcus aureus skin and soft-tissue infectionsInfection Control and Hospital Epidemiology. 2014; 35(10):1251-1256. 

Schlett CD, Millar EV, Crawford KB, et al. Prevalence of chlorhexidine-resistant methicillin-resistant Staphylococcus aureus following prolonged exposureAntimicrobial Agents and Chemotherapy. 2014; 58(8):4404-4410. 

Ellis MW, Schlett CD, Millar EV, et al. Hygiene strategies to prevent methicillin-resistant Staphylococcus aureus skin and soft-tissue infections: A cluster-randomized controlled trial among high-risk military traineesClinical Infectious Diseases. 2014; 51(11):1540-1548.

Ellis MW, Johnson R, Crawford KB, et al. Molecular characterization of a catalase-negative methicillin-susceptible Staphylococcus aureus subsp. aureus strain collected from a patient with cutaneous abscess. Journal of Clinical Microbiology. 2014; 52(1):344-346.

Johnson R, Ellis MW, Lanier JB, et al.  Correlation between nasal microbiome composition and remote purulent skin and soft tissue infectionsInfection and Immunity. 2015; 83(2):802-811.

D’Onofrio MJ, Schlett CD, Millar EV, et al. Reduction in acute gastroenteritis among military trainees: Secondary effects of a hygiene-based cluster-randomized trial for skin and soft tissue infection prevention. Infection Control and Hospital Epidemiology. In Press. doi: 10.1017/ice.2014.65.

Millar EV, Chen W, Schlett CD, et al.  Frequent use of chlorhexidine-based body wash associated with a reduction in methicillin-resistant Staphylococcus aureus (MRSA) nasal colonization among military trainees. Clinical Infectious Diseases. In Press. doi: 10.1128/AAC.03993-14.

Heaton SM, Weintrob AC, Downing K, Keenan B, Aggarwal D, Shaikh F, Tribble DR, Wells J, and the IDCRP TIDOS Group. Histopathological Techniques for the Diagnosis of Combat-Related Invasive Fungal Wound Infections. BMC Clinical Pathology. 2016; 16:11.

Presentations 2014

Ellis MW, Schlett CD, Cui T, et al. Epidemiology of skin and soft-tissue infections in US Army trainees at Fort Benning. ID Week, A Joint Meeting of IDSA, SHEA, HIVMA, and PIDS, 8-12 October 2014, Philadelphia, PA.

Ellis MW, Chen W, Millar EV, et al. Routine use of chlorhexidine-based body wash associated with a reduction in methicillin-resistant Staphylococcus aureus nasal colonization among military trainees.  ID Week, A Joint Meeting of IDSA, SHEA, HIVMA, and PIDS, 8-12 October 2014, Philadelphia, PA.

D’Onofrio MJ, Schlett CD, Millar EV, et al. Reduction in acute gastrointestinal infection among military trainees: Secondary effects of a hygiene-based cluster-randomized trial for SSTI prevention.  ID Week, A Joint Meeting of IDSA, SHEA, HIVMA, and PIDS, 8-12 October 2014, Philadelphia, PA.

Ellis MW, Lanier JB, Schlett CD, et al. Combating Staphylococcal skin and soft-tissue infections in trainees at Fort Benning.  Military Health System Research Symposium, 18-21 August 2014, Fort Lauderdale, FL.

Ellis MW, Schlett CD, Millar EV, et al. Epidemiology of skin and soft-tissue infections in trainees at Fort Benning.  Military Health System Research Symposium, 18-21 August 2014, Fort Lauderdale, FL.

Johnson R, Lanier JB, Schlett CD, et al.  Impact of the nasal microbiome on the development of Staphylococcal skin and soft-tissue infections at Fort Benning.  114th General Meeting of the American Society for Microbiology, 17-20 May 2014, Boston, MA; and Military Health System Research Symposium, 18-21 August 2014, Fort Lauderdale, FL.