Wound infection is a complication of deployment and battlefield injuries that can lead to significant morbidity and mortality. During the recent wars in Afghanistan (Operation Enduring Freedom) and Iraq (Operation Iraqi Freedom and New Dawn), the deployment of forward surgical assets, utilization of rapid evacuation to medical care, and use of body armor have culminated in a greater number of casualties surviving their initial injury. As an unintended consequence, a high incidence of infections among the wounded warriors has been reported. In addition, mechanisms of injury have changed over the years, resulting in a greater number of severe, complex wounds from improvised explosive devices. This has led to a higher rate of injuries involving the extremities, including limb loss. In response to the severity of injuries, broader spectrum antimicrobials have been increasingly used to treat these battlefield wounds after reaching medical care. Further adding to the complexity of wound management is the occurrence of multidrug-resistant organisms and/or virulent pathogens. Lastly, late onset or recurrent infections, such as skin and soft-tissue or osteomyelitis, lead to further morbidity and healthcare costs.
Although some studies have evaluated infections in war-wounded subjects from the recent wars in Afghanistan and Iraq, these studies are limited by several factors. First, the studies are mostly from single centers and have not evaluated factors across multiple levels of care from the battlefield to treatment facilities in the U.S. to follow up after initial discharge and to further care through the Veterans Affairs (VA) system. Second, the information gathered in the published studies has not been comprehensive including information on both surgical management and medical management with a focus on microbiology results and antibiotic administration. Further, the studies have not used a priori definitions of infectious disease syndromes. Lastly, the studies have not focused on outcomes. Given that randomized, controlled trials would be difficult to conduct in a protected population with severe injuries, comprehensive studies on combat-related trauma infections with systematic data collection across multiple levels of care are needed in order to mimic clinical trials and inform prevention and treatment efforts. To address these research gaps, IDCRP conducts multiple studies on trauma related infections.
IDCRP-024: Trauma Infectious Disease Outcomes Study (TIDOS)
The development of infectious complications among military personnel following combat-related trauma remains a frequent occurrence. As military personnel shifted to different operational theaters, injury patterns, severity, and mechanisms changed resulting in unexpected complications, such as the increased number of cases of invasive fungal infections (IFIs) among combat casualties who sustained complex dismounted blast trauma. Moreover, the rising proportion of colonization by multidrug-resistant organisms (MDROs) creates further difficulties for clinicians. Using prospective data gained from a cohort of military personnel with deployment-related injuries has provided further understanding of risk factors, treatment strategies, and outcomes associated with infectious complications and support improvement in the prevention and management of infections.
On June 1, 2009, the U.S. Department of Defense (DoD) – Department of Veterans Affairs, Trauma Infectious Disease Outcomes Study (TIDOS) was initiated. This ongoing multisite project is an observational cohort study of short- and long-term infectious complications among U.S. military personnel with traumatic injuries sustained during deployment. Enrolled patients are prospectively followed for a period of five years. Patients are eligible for inclusion if they are either active duty personnel or DoD beneficiaries, at least 18 years of age, injured during deployment requiring medical evacuation to Landstuhl Regional Medical Center (LRMC) in Germany before transfer to a participating U.S. military hospitals, and provide informed consent (or surrogate consent through legally authorized representative). In addition, as part of TIDOS, bacterial isolates collected from wounded military personnel are stored in a repository for research purposes. In recent years, TIDOS microbiology projects have expanded to include analyses investigating bacterial antagonism in wounds, anaerobic bacterial infections, presence of antibiotic resistance genes/virulence mechanisms and their association with antibiotics and clinical outcomes, and biofilm dispersal. Overall, the TIDOS team has continued efforts to provide information to the U.S. Army Institute of Surgical Research Joint Trauma System in support of clinical practice guidelines and process improvement initiatives.
IDCRP-077: The Evaluation of Molecular and Antigen Based Techniques for the Identification of Invasive Skin and Soft Tissue Infections Due to Fungi
IDCRP-044: Case-Control Study of Osteomyelitis Risk Factors and Clinical Outcome Predictors Following an Operation Iraqi Freedom/ Operation Enduring Freedom Related Orthopedic Injury
IDCRP-072: Treatment Protocol for the Use of Arbekacin in Adult Patients with Infections Caused by Multidrug-resistant Bacteria
- Developed and executed the TIDOS Infectious Disease module to supplement the DoD Trauma Registry.
- Support Senior-level responses to queries for Wounded Warrior care and outcomes (e.g., Congressional queries/testimony/presentations and VA Institute of Medicine report on Blast injury).
- Generated the Invasive Fungal Wound Infections (IFI) Outbreak Investigation Technical Report and provided a briefing at Pentagon. These data were used to develop the Joint Trauma System Clinical Practice Guideline to Prevent and Manage IFIs. After publishing a comprehensive review in 2014 on the subject, an updated executive summary on IFI research was sent to the Pentagon.
- Provide assessments of adherence and outcomes of DoD Joint Trauma System clinical practice guidelines.
- Informed Wounded Warrior Infection Control policy evaluation of multi-drug resistant gram negative pathogens active surveillance for colonization (Medical Surveillance Monthly Report).
- Microbiological studies in support of DoD-Global Emerging Infection Surveillance (GEIS) Multi-drug Resistant Organism (MDRO) surveillance and Military Infectious Disease Research Program (MIDRP) initiatives to advance prevention/treatment products for the warfighter.
Partners and Collaborators
IDCRP collaborates with investigators across various specialties (e.g., infectious disease, trauma surgery, and orthopedics) and commands at Landstuhl Regional Medical Center (LRMC), Walter Reed National Military Medical Center (WRNMMC), San Antonio Military Medical Center (SAMMC), US Army Institute for Surgical Research (USAISR), Walter Reed Army Institute of Research, Naval Medical Research Center, St. Louis Veterans Affairs (VA) Medical Center, and the Uniformed Services University of the Health Sciences.
TIDOS US-UK Collaboration
The primary aim of the US-UK Military Combat Trauma Extremity Wound Infection Comparative Analysis is to inform future guidance and real-time tools for combat-related wound infection surveillance, prevention, and treatment. Both forces have sustained significant number of complex blast injuries, increasing the risk of infectious complications. Similarly, both militaries have relied on combat trauma registries to inform real-time improvements in prevention and management of battlefield injuries. System-wide efforts have also been undertaken by both militaries to survey and analyze wound infections (US - Trauma Infectious Disease Outcomes Study [TIDOS]; UK - Wound Infection Surveillance Program or WISP). Many surgical and medical practices are approached similarly; however, there are important differences including medevac/patient movement, damage control orthopedic surgery, wound care (e.g., negative pressure wound therapy; NPWT), and post-injury antibiotic prophylaxis selection that warrant collaborative analyses. Joint proposal and data-sharing agreements are currently under review. Initial analysis will focus on findings and management approaches for blast-related invasive fungal wound infections which affected both forces.
Tribble DR, Conger NG, Fraser S, Gleeson TD, Wilkins K, Antonille T, Weintrob A, Ganesan A, Gaskins LJ, Li P, Grandits G, Landrum ML, Hospenthal DR, Millar EV, Blackbourne LH, Dunne JR, Craft D, Mende K, Wortmann GW, Herlihy R, McDonald J, and Murray CK. Infection-associated clinical outcomes in hospitalized medical evacuees after traumatic injury: trauma infectious disease outcome study. Journal of Trauma. 2011 Jul;71(1 Suppl):S33-S42.
Tribble DR, Lloyd B, Weintrob A, Ganesan A, Murray CK, Li P, Bradley W, Fraser S, Warkentien T, Gaskins LJ, Seillier-Moiseiwitsch F, Millar EV, Hospenthal DR; and the IDCRP TIDOS group. Antimicrobial prescribing practices following publication of guidelines for the prevention of infections associated with combat-related injuries. Journal of Trauma. 2011 Aug;71(2 Suppl 2):S299-S306.
Warkentien T, Rodriguez C, Lloyd B, Wells J, Weintrob A, Dunne JR, Ganesan A, Li P, Bradley W, Gaskins LJ, Seillier-Moiseiwitsch F, Murray CK, Millar EV, Keenan B, Paolino K, Hospenthal DR, and Tribble DR for the IDCRP TIDOS Group. Invasive Mold Infections following Combat-related Injuries. Clinical Infectious Diseases. 2012; 55(11):1441-1449.
Tribble DR, Rodriguez C, Warkentien T for the IDCRP TIDOS Investigative Team. Mucormycosis After a Tornado in Joplin, Missouri. New England Journal of Medicine. 2013; 368(11):1067. [letter to the editor]
Ganesan A, Crawford K, Mende K, Murray CK, Lloyd BA, Ellis M, Tribble DR, and Weintrob AC. Evaluation for a Novel Methicillin Resistance (mecC) Homologue in Methicillin-Resistant Staphylococcus aureus Isolates Obtained from Injured Military Personnel. Journal of Clinical Microbiology. 2013; 51(9):3073-3075.
Weintrob AC, Murray CK, Lloyd B, Li P, Lu D, Miao Z, Aggarwal D, Carson ML, Gaskins L, and Tribble DR. Active Surveillance for Asymptomatic Colonization with Multidrug-Resistant Gram-Negative Bacilli among Injured Service Members - A Three-Year Evaluation. Medical Surveillance Monthly Report. 2013; 20(8):17-22.
Lloyd BA, Weintrob AC, Hinkle M, Fortuna G, Murray CK, Bradley W, Millar EV, Shaikh F, Vanderzant K, Gregg S, Lloyd G, Stevens J, Carson ML, Aggarwal D, and Tribble DR. Adherence to Published Antimicrobial Prophylaxis Guidelines for Wounded Service Members in the Ongoing Conflicts in Southwest Asia. Military Medicine. 2014; 179(3):324-328.
Akers KS, Mende K, Cheatle K, Zera W, Yu X, Beckius M, Aggarwal D, Li P, Sanchez C, Wenke JC, Weintrob AC, Tribble DR, Murray CK, and the IDCRP TIDOS Group. Biofilms and Persistent Wound Infections in United States Military Trauma Patients: A Case-Control Analysis. BMC Infectious Diseases. 2014; 14:190.
Rini EA, Weintrob AC, Tribble DR, Lloyd BA, Warkentien TE, Shaikh F, Li P, Aggarwal D, Carson ML, Murray CK and the IDCRP TIDOS Group. Compliance with Antimalarial Chemoprophylaxis Recommendations for Wounded United States Military Personnel Admitted to a Military Treatment Facility. American Journal of Tropical Medicine and Hygiene. 2014; 90(6):1113-1116.
Rodriguez C, Weintrob AC, Shah J, Malone D, Dunne JR, Weisbrod AB, Lloyd BA, Warkentien T, Murray CK, Wilkins K, Shaikh F, Carson ML, Aggarwal D, Tribble DR and the IDCRP TIDOS Group. Risk Factors Associated with Invasive Fungal Infections in Combat Trauma. Surgical Infections. 2014; 15(5):521-526.
Lloyd BA, Weintrob AC, Rodriguez C, Dunne J, Weisbrod AB, Hinkle M, Warkentien T, Murray CK, Oh J, Millar EV, Shah J, Shaikh F, Gregg S, Lloyd G, Stevens J, Carson ML, Aggarwal D, Tribble DR and the IDCRP TIDOS Group. Effect of Early Screening for Invasive Fungal Infections in U.S. Service Members with Explosive Blast Injuries. Surgical Infections. 2014; 15(5):619-626.
Mende K, Beckius M, Zera WC, Yu X, Cheatle KA, Aggarwal D, Li P, Lloyd BA, Tribble DR, Weintrob AC, and Murray CK. Phenotypic and Genotypic Changes over Time and across Facilities of Serial Colonizing and Infecting Escherichia coli Isolates Recovered from Injured Service Members. Journal of Clinical Microbiology. 2014; 52(11):3869-3877.
Rodriguez C, Weintrob AC, Dunne JR, Weisbrod AB, Lloyd BA, Warkentien T, Malone D, Wells J, Murray CK, Bradley W, Shaikh F, Shah J, Carson ML, Aggarwal D, Tribble DR and the IDCRP TIDOS Group. Clinical Relevance of Mold Culture Positivity With and Without Recurrent Wound Necrosis Following Combat-Related Injuries. Journal of Trauma. 2014; 77(5):769-773.
Tribble DR and Rodriguez CJ. Combat-related Invasive Fungal Wound Infections. Current Fungal Infection Reports. 2014; 8(4):277-286.
Blyth DM, Mende K, Weintrob AC, Beckius ML, Zera WC, Bradley W, Lu D, Tribble DR, Murray CK, and the IDCRP TIDOS Group. Resistance Patterns and Clinical Significance of Candida Colonization and Infections in Combat-Related Injured Patients from Iraq and Afghanistan. Open Forum Infectious Diseases. 2014; 1(3): doi: 10.1093/ofid/ofu109.
Weintrob AC, Weisbrod AB, Dunne JR, Rodriguez C, Malone D, Lloyd BA, Warkentien T, Wells J, Murray CK, Bradley W, Shaikh F, Shah J, Aggarwal D, Carson ML, Tribble DR and the IDCRP TIDOS Group. Combat Trauma-Associated Invasive Fungal Wound Infections: Epidemiology and Clinical Classification. Epidemiology and Infection. 2015; 143(1):214-224.
Yun HC, Weintrob AC, Conger NG, Li P, Lu D, Tribble DR, Murray CK and the IDCRP TIDOS Group. Healthcare-Associated Pneumonia among U.S. Combat Casualties, 2009 to 2010. Military Medicine. 2015; 180(1):104-110.
Warkentien TE, Shaikh F, Weintrob AC, Rodriguez CJ, Murray CK, Lloyd BA, Ganesan A, Aggarwal D, Carson ML, and Tribble DR on behalf of the IDCRP TIDOS Group. Impact of Mucorales and Other Invasive Molds on Clinical Outcomes of Polymicrobial Traumatic Wound Infections. Journal of Clinical Microbiology. 2015; 53(7): 2262-2270.
Tribble DR, Rodriguez CJ, Weintrob AC, Murray, CK, Aggarwal D, Shaikh F, Carson ML, Masuoka P, and the IDCRP TIDOS Group. Environmental Factors Related to Fungal Wound Contamination after Combat Trauma in Afghanistan, 2009-2011. Emerging Infectious Diseases. 2015; 21(10):1750-1760.
Blyth DM, Yun HC, Tribble DR, and Murray CK. Lessons of War: Combat-related Injury Infections during the Vietnam War and Operation Iraqi and Enduring Freedom. Journal of Trauma and Acute Care Surgery. 2015; 79(4 Suppl 2):S227-S235.
White BK, Mende K, Weintrob AC, Beckius ML, Zera WC, Lu D, Bradley W, Tribble DR, Schnaubelt E, and Murray CK on behalf of the IDCRP TIDOS Group. Epidemiology and Antimicrobial Susceptibilities of Wound Isolates of Obligate Anaerobes from Combat Casualties. Diagnostic Microbiology and Infectious Disease. 2016; 84(2): 144-150.
Lewis CJ, Li P, Stewart L, Weintrob AC, Carson ML, Murray CK, Tribble DR, and Ross JD. Tranexamic Acid in Life-Threatening Military Injury and the Associated Risk for Infectious Complications. British Journal of Surgery. 2016; 103(4): 366-373.
Gilbert LJ, Li P, Murray CK, Yun HC, Aggarwal D, Weintrob AC, Tribble DR, and the IDCRP TIDOS Group. Multidrug-Resistant Gram-Negative Bacilli Colonization Risk Factors among Trauma Patients. Diagnostic Microbiology and Infectious Diseases. 2016; 84(4): 358-360
Mende K, Beckius ML, Zera WC, Yu X, Li P, Tribble DR, and Murray CK for the IDCRP TIDOS Investigative Team. Lack of Doxycycline Antimalarial Prophylaxis Impact on Staphylococcus aureus Tetracycline Resistance. Diagnostic Microbiology and Infectious Disease. 2016; 86(2):211-22
Tribble DR, Li P, Warkentien T, Lloyd BA, Schnaubelt ER, Ganesan A, Bradley W, Aggarwal D, Carson ML, Weintrob AC, and Murray CK. Impact of Operational Theater on Combat and Noncombat Trauma-Related Infections. Military Medicine. 2016; 181(10): 1258-1268.
Lloyd, B. A., et al. (2017). "Variation in Postinjury Antibiotic Prophylaxis Patterns Over Five Years in a Combat Zone." Mil Med 182(S1): 346-352.
Campbell, W. R., et al. (2017). "Multi-Drug–Resistant Gram-Negative Infections in Deployment-Related Trauma Patients." Surg Infect (Larchmt) 18(3): 357-367.