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Introduction: During Operation Enduring Freedom in Afghanistan, an outbreak of combat-related invasive fungal wound infections (IFIs) emerged among casualties with dismounted blast trauma and became a priority issue for the Military Health System., Methods: In 2011, the Trauma Infectious Disease Outcomes Study (TIDOS) team led the Department of Defense IFI outbreak investigation to describe characteristics of IFIs among combat casualties and provide recommendations related to management of the disease. To support the outbreak investigation, existing IFI definitions and classifications utilized for immunocompromised patients were modified for use in epidemiologic research in a trauma population. Following the conclusion of the outbreak investigation, multiple retrospective analyses using a population of 77 IFI patients (injured during June 2009 to August 2011) were conducted to evaluate IFI epidemiology, wound microbiology, and diagnostics to support refinement of Joint Trauma System (JTS) clinical practice guidelines. Following cessation of combat operations in Afghanistan, the TIDOS database was comprehensively reviewed to identify patients with laboratory evidence of a fungal infection and refine the IFI classification scheme to incorporate timing of laboratory fungal evidence and include categories that denote a high or low level of suspicion for IFI. The refined IFI classification scheme was utilized in a large-scale epidemiologic assessment of casualties injured over a 5.5-year period., Results: Among 720 combat casualties admitted to participating hospitals (2009-2014) who had histopathology and/or wound cultures collected, 94 (13%) met criteria for an IFI and 61 (8%) were classified as high suspicion of IFI. Risk factors for development of combat-related IFIs include sustaining a dismounted blast injury, experiencing a traumatic transfemoral amputation, and requiring resuscitation with large-volume (>20 units) blood transfusions. Moreover, TIDOS analyses demonstrated the adverse impact of IFIs on wound healing, particularly with order Mucorales. A polymerase chain reaction (PCR)-based assay to identify filamentous fungi and support earlier IFI diagnosis was also assessed using archived formalin-fixed, paraffin-embedded tissue specimens. Although the PCR-based assay had high specificity (99%), there was low sensitivity (63%); however, sensitivity improved to 83% in tissues collected from sites with angioinvasion. Data obtained from the initial IFI outbreak investigation (37 IFI patients) and subsequent TIDOS analyses (77 IFI patients) supported development and refinement of a JTS clinical practice guideline for the management of IFIs in war wounds. Furthermore, a local clinical practice guideline to screen for early tissue-based evidence of IFIs among blast casualties at the Landstuhl Regional Medical Center was critically evaluated through a TIDOS investigation, providing additional clinical practice support. Through a collaboration with the Uniformed Services University Surgical Critical Care Initiative, findings from TIDOS analyses were used to support development of a clinical decision support tool to facilitate early risk stratification., Conclusions: Combat-related IFIs are a highly morbid complication following severe blast trauma and remain a threat for future modern warfare. Our findings have supported JTS clinical recommendations, refined IFI classification, and confirmed the utility of PCR-based assays as a complement to histopathology and/or culture to promote early diagnosis. Analyses underway or planned will add to the knowledge base of IFI epidemiology, diagnostics, prevention, and management., (Published by Oxford University Press on behalf of the Association of Military Surgeons of the United States 2022. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Background: The Joint Trauma System (JTS) is a DoD Center of Excellence for Military Health System trauma care delivery and the DoD's reference body for trauma care in accordance with National Defense Authorization Act for Fiscal Year 2017. Through the JTS, evidence-based clinical practice guidelines (CPGs) have been developed and subsequently refined to standardize and improve combat casualty care. Data are amassed through a single, centralized DoD Trauma Registry to support process improvement measures with specialty modules established as the registry evolved. Herein, we review the implementation of the JTS DoD Trauma Registry specialty Infectious Disease Module and the development of infection-related CPGs and summarize published findings on the subsequent impact of the Infectious Disease Module on combat casualty care clinical practice and guidelines., Methods: The DoD Trauma Registry Infectious Disease Module was developed in collaboration with the Infectious Disease Clinical Research Program (IDCRP) Trauma Infectious Disease Outcomes Study (TIDOS). Infection-related information (e.g., syndromes, antibiotic management, and microbiology) were collected from military personnel wounded during deployment June 1, 2009 through December 31, 2014 and medevac'd to Landstuhl Regional Medical Center in Germany before transitioning to participating military hospitals in the USA., Results: To support process improvements and reduce variation in practice patterns, data collected through the Infectious Disease Module have been utilized in TIDOS analyses focused on assessing compliance with post-trauma antibiotic prophylaxis recommendations detailed in JTS CPGs. Analyses examined compliance over three time periods: 6 months, one-year, and 5 years. The five-year analysis demonstrated significantly improved adherence to recommendations following the dissemination of the 2011 JTS CPG, particularly with open fractures (34% compliance compared to 73% in 2013-2014). Due to conflicting recommendations regarding use of expanded Gram-negative coverage with open fractures, infectious outcomes among patients with open fractures who received cefazolin or expanded Gram-negative coverage (cefazolin plus fluoroquinolones and/or aminoglycosides) were also examined in a TIDOS analysis. The lack of a difference in the proportion of osteomyelitis (8% in both groups) and the significantly greater recovery of Gram-negative organisms resistant to aminoglycosides or fluoroquinolones among patients who received expanded Gram-negative coverage supported JTS recommendations regarding the use of cefazolin with open fractures. Following recognition of the outbreak of invasive fungal wound infections (IFIs) among blast casualties injured in Afghanistan, the ID Module was refined to capture data (e.g., fungal culture and histopathology findings, wound necrosis, and antifungal management) needed for the TIDOS team to lead the DoD outbreak investigation. These data captured through the Infectious Disease Module provided support for the development of a JTS CPG for the prevention and management of IFIs, which was later refined based on subsequent TIDOS IFI analyses., Conclusions: To improve combat casualty care outcomes and mitigate high-consequence infections in future conflicts, particularly in the event of prolonged field care, expansion, refinement, and a mechanism for sustainability of the DoD Trauma Registry Infectious Disease Module is needed to include real-time surveillance of infectious disease trends and outcomes., (Published by Oxford University Press on behalf of the Association of Military Surgeons of the United States 2022. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Introduction: Extremity trauma is the most common battlefield injury, resulting in a high frequency of combat-related extremity wound infections (CEWIs). As these infections are associated with substantial morbidity and may impact wounded warriors long after initial hospitalization, CEWIs have been a focus of the Infectious Disease Clinical Research Program (IDCRP). Herein, we review findings of CEWI research conducted through the IDCRP and discuss future and ongoing analyses., Methods: Military personnel with deployment-related trauma sustained between 2009 and 2014 were examined in retrospective analyses through the observational Trauma Infectious Disease Outcomes Study (TIDOS). Characteristics of wounded warriors with ≥1 open extremity wound were assessed, focusing on injury patterns and infection risk factors. Through a separate trauma-associated osteomyelitis study, military personnel with combat-related open fractures of the long bones (tibia, femur, and upper extremity) sustained between 2003 and 2009 were examined to identify osteomyelitis risk factors., Results: Among 1,271 wounded warriors with ≥1 open extremity wound, 16% were diagnosed with a CEWI. When assessed by their most severe extremity injury (i.e., amputation, open fracture, or open soft-tissue wound), patients with amputations had the highest proportion of infections (47% of 212 patients with traumatic amputations). Factors related to injury pattern, mechanism, and severity were independent predictors of CEWIs during initial hospitalization. Having a non-extremity infection at least 4 days before CEWI diagnosis was associated with reduced likelihood of CEWI development. After hospital discharge, 28% of patients with extremity trauma had a new or recurrent CEWI during follow-up. Risk factors for the development of CEWIs during follow-up included injury pattern, having either a CEWI or other infection during initial hospitalization, and receipt of antipseudomonal penicillin for ≥7 days. A reduced likelihood for CEWIs during follow-up was associated with a hospitalization duration of 15-30 days. Under the retrospective osteomyelitis risk factor analysis, patients developing osteomyelitis had higher open fracture severity based on Gustilo-Anderson (GA) and the Orthopaedic Trauma Association classification schemes and more frequent traumatic amputations compared to open fracture patients without osteomyelitis. Recurrence of osteomyelitis was also common (28% of patients with open tibia fractures had a recurrent episode). Although osteomyelitis risk factors differed between the tibia, femur, and upper extremity groups, sustaining an amputation, use of antibiotic beads, and being injured in the earlier years of the study (before significant practice pattern changes) were consistent predictors. Other risk factors included GA fracture severity ≥IIIb, blast injuries, foreign body at fracture site (with/without orthopedic implant), moderate/severe muscle damage and/or necrosis, and moderate/severe skin/soft-tissue damage. For upper extremity open fractures, initial stabilization following evacuation from the combat zone was associated with a reduced likelihood of osteomyelitis., Conclusions: Forthcoming studies will examine the effectiveness of common antibiotic regimens for managing extremity deep soft-tissue infections to improve clinical outcomes of combat casualties and support development of clinical practice guidelines for CEWI treatment. The long-term impact of extremity trauma and resultant infections will be further investigated through both Department of Defense and Veterans Affairs follow-up, as well as examination of the impact on comorbidities and mental health/social factors., (Published by Oxford University Press on behalf of the Association of Military Surgeons of the United States 2022. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Background: In the aftermath of wars, there is a surge in the number of wounded service members who leave active duty and become eligible for healthcare through the Department of Veterans Affairs (VA). Collaborations between the Department of Defense (DoD) and VA are crucial to capture comprehensive data and further understand the long-term impact of battlefield trauma. We provide a summary of the development, methodology, and status of an effective collaboration between the Infectious Disease Clinical Research Program and the St. Louis VA Health Care System with the multicenter, observational Trauma Infectious Disease Outcomes Study (TIDOS), which examines the short- and long-term outcomes of deployment-related trauma., Methods: As part of TIDOS, wounded service members who transitioned to participating military hospitals in the United States (2009-2014) were given the opportunity to enroll in a prospective follow-up cohort study to continue to capture infection-related data after their hospital discharge. Enrollees in the TIDOS cohort who left military service and received health care through the VA also had the option of consenting to have relevant VA medical records abstracted and included with the study data. Infections considered to be complications resulting from the initial trauma were examined., Results: Among 1,336 TIDOS enrollees, 1,221 (91%) registered and received health care through the VA with 633 (47%) consenting to follow-up using VA records and comprising the TIDOS-VA cohort. Of the first 337 TIDOS-VA cohort enrollees, 38% were diagnosed with a new trauma-related infection following hospital discharge (median: 88 days; interquartile range: 18-351 days). Approximately 71% of the infections were identified through DoD sources (medical records and follow-up) and 29% were identified through VA electronic medical records, demonstrating the utility of DoD-VA collaborations. The TIDOS DoD-VA collaboration has also been utilized to assess intermediate and long-term consequences of specific injury patterns. Among 89 TIDOS-VA cohort enrollees with genitourinary trauma, 36% reported sexual dysfunction, 21% developed at least one urinary tract infection, 14% had urinary retention/incontinence, and 8% had urethral stricture. The rate of urinary tract infections was 0.05/patient-year during DoD follow-up time and 0.07/patient-year during VA follow-up time., Conclusions: Wider capture of infection-related outcome data through the DoD-VA collaboration provided a clearer picture of the long-term infection burden resulting from deployment-related trauma. Planned analyses include assessment of osteomyelitis among combat casualties with amputations and/or open fractures, evaluation of mental health and social factors related to injury patterns, and examination of health care utilization and cost in relation to infectious disease burdens., (Published by Oxford University Press on behalf of the Association of Military Surgeons of the United States 2022. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Introduction: During the wars in Iraq and Afghanistan, increased incidence of multidrug-resistant (MDR) organisms, as well as polymicrobial wounds and infections, complicated the management of combat trauma-related infections. Multidrug resistance and wound microbiology are a research focus of the Trauma Infectious Disease Outcomes Study (TIDOS), an Infectious Disease Clinical Research Program, Uniformed Services University, research protocol. To conduct comprehensive microbiological research with the goal of improving the understanding of the complicated etiology of wound infections, the TIDOS MDR and Virulent Organisms Trauma Infections Initiative (MDR/VO Initiative) was established as a collaborative effort with the Brooke Army Medical Center, Naval Medical Research Center, U.S. Army Institute of Surgical Research, and Walter Reed Army Institute of Research. We provide a review of the TIDOS MDR/VO Initiative and summarize published findings., Methods: Antagonism and biofilm formation of commonly isolated wound bacteria (e.g., ESKAPE pathogens-Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp.), antimicrobial susceptibility patterns, and clinical outcomes are being examined. Isolates collected from admission surveillance swabs, as part of infection control policy, and clinical infection workups were retained in the TIDOS Microbiological Repository and associated clinical data in the TIDOS database., Results: Over the TIDOS study period (June 2009 to December 2014), more than 8,300 colonizing and infecting isolates were collected from military personnel injured with nearly one-third of isolates classified as MDR. At admission to participating U.S. military hospitals, 12% of wounded warriors were colonized with MDR Gram-negative bacilli. Furthermore, 27% of 913 combat casualties with ≥1 infection during their trauma hospitalization had MDR Gram-negative bacterial infections. Among 335 confirmed combat-related extremity wound infections (2009-2012), 61% were polymicrobial and comprised various combinations of Gram-negative and Gram-positive bacteria, yeast, fungi, and anaerobes. Escherichia coli was the most common Gram-negative bacilli isolated from clinical workups, as well as the most common colonizing MDR secondary to extended-spectrum β-lactamase resistance. Assessment of 479 E. coli isolates collected from wounded warriors found 188 pulsed-field types (PFTs) from colonizing isolates and 54 PFTs from infecting isolates without significant overlap across combat theaters, military hospitals, and study years. A minority of patients with colonizing E. coli isolates developed subsequent infections with the same E. coli strain. Enterococcus spp. were most commonly isolated from polymicrobial wound infections (53% of 204 polymicrobial cultures). Patients with Enterococcus infections were severely injured with a high proportion of lower extremity amputations and genitourinary injuries. Approximately 65% of polymicrobial Enterococcus infections had other ESKAPE organisms isolated. As biofilms have been suggested as a cause of delayed wound healing, wound infections with persistent recovery of bacteria (isolates of same organism collected ≥14 days apart) and nonrecurrent bacterial isolates were assessed. Biofilm production was significantly associated with recurrent bacteria isolation (97% vs. 59% with nonrecurrent isolates; P < 0.001); however, further analysis is needed to confirm biofilm formation as a predictor of persistent wound infections., Conclusions: The TIDOS MDR/VO Initiative provides comprehensive and detailed data of major microbial threats associated with combat-related wound infections to further the understanding of wound etiology and potentially identify infectious disease countermeasures, which may lead to improvements in combat casualty care., (© The Association of Military Surgeons of the United States 2022. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: During recent wars in Iraq and Afghanistan, improved survivability in severe trauma corresponded with a rise in the proportion of trauma-related infections, including those associated with multidrug-resistant organisms (MDROs). Significant morbidity was reported in association with the infections. There is also concern regarding potential long-term impacts of the trauma-related infectious complications. Therefore, to meet the critical need of prospective collection of standardized infection-related data to understand the disease burden and improve outcomes of wounded personnel, the Trauma Infectious Disease Outcomes Study (TIDOS) was developed. Herein, we review accomplishments and key peer-reviewed findings of TIDOS., Methods: The TIDOS project is a multicenter observational study of short- and long-term infectious complications following deployment-related trauma. Wounded military personnel medevac'd to Landstuhl Regional Medical Center (LRMC; Germany) before transfer to a participating US military hospital between June 2009 and December 2014 were eligible for inclusion. An infectious disease module to supplement the Department of Defense Trauma Registry by collecting infection-related data from all trauma patients admitted to participating hospitals was developed. Specimens from trauma patients were also collected and retained in a microbiological isolate repository. During the initial hospitalization, patients were given the opportunity to enroll in a prospective follow-up cohort study. Patients who received Department of Veterans Affairs (VA) care were also given the opportunity to consent to ongoing VA follow-up., Results: A total of 2,699 patients transferred to participating military hospitals in the USA, of which 1,359 (50%) patients enrolled in the TIDOS follow-up cohort. In addition, 638 enrolled in the TIDOS-VA cohort (52% of TIDOS enrollees who entered VA healthcare). More than 8,000 isolates were collected from infection control surveillance and diagnostic evaluations and retained in the TIDOS Microbiological Repository. Approximately 34% of the 2,699 patients at US hospitals developed a trauma-related infection during their initial hospitalization with skin and soft-tissue infections being predominant. After discharge from the US hospitals, approximately one-third of TIDOS cohort enrollees developed a new trauma-related infection during follow-up and extremity wound infections (skin and soft-tissue infections and osteomyelitis) continued to be the majority. Among TIDOS cohort enrollees who received VA healthcare, 38% developed a new trauma-related infection with the incident infection being diagnosed a median of 88 days (interquartile range: 19-351 days) following hospital discharge. Data from TIDOS have been used to support the development of Joint Trauma System clinical practice guidelines for the prevention of combat-related infections, as well as the management of invasive fungal wound infections. Lastly, due to the increasing proportion of infections associated with MDROs, TIDOS investigators have collaborated with investigators across military laboratories as part of the Multidrug-Resistant and Virulent Organisms Trauma Infections Initiative with the objective of improving the understanding of the complex wound microbiology in order to develop novel infectious disease countermeasures., Conclusions: The TIDOS project has focused research on four initiatives: (1) blast-related wound infection epidemiology and clinical management; (2) DoD-VA outcomes research; (3) Multidrug- Resistant and other Virulent Organisms Trauma Infections Initiative; and (4) Joint Trauma System clinical practice guidelines and antibiotic stewardship. There is a continuing need for longitudinal data platforms to support battlefield wound research and clinical practice guideline recommendation refinement, particularly to improve care for future conflicts. As such, maintaining a research platform, such as TIDOS, would negate the lengthy time needed to initiate data collection and analysis., (Published by Oxford University Press on behalf of the Association of Military Surgeons of the United States 2019. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Objectives: Functional gastrointestinal disorders (FGDs) are recognized sequelae of infectious gastroenteritis (IGE). Within the active duty military population, a group with known high IGE rates, the population-based incidence, risk factors, and attributable burden of care referable to FGD after IGE are poorly defined., Methods: Using electronic medical encounter data (1999-2007) on active duty US military, a matched, case-control study describing the epidemiology and risk determinants of FGD (irritable bowel syndrome (IBS), functional constipation (FC), functional diarrhea (FD), dyspepsia (D)) was conducted. Incidence rates and duration of FGD-related medical care were estimated, and conditional logistic regression was utilized to evaluate FGD risk after IGE., Results: A total of 31,866 cases of FGD identified were distributed as follows: FC 55% (n=17,538), D 21.2% (n=6,750), FD 2.1% (n=674), IBS 28.5% (n=9,091). Previous IGE episodes were distributed as follows: specific bacterial pathogen (n=65, 1.2%), bacterial, with no pathogen specified (n=2155, 38.9%), protozoal (n=38, 0.7%), viral (n=3431, 61.9%). A significant association between IGE and all FGD (odds ratio (OR) 2.64; P<0.001) was seen, with highest risk for FD (OR 6.28, P<0.001) and IBS (OR 3.72, P<0.001), and moderate risk for FC (2.15, P<0.001) and D (OR 2.39, P<0.001). Risk generally increased with temporal proximity to, and bacterial etiology of, exposure. Duration of FGD-related care was prolonged with 22.7% having FGD-associated medical encounters 5 years after diagnosis., Conclusions: FGD are common in this population at high risk for IGE. When considering effective countermeasures and mitigation strategies, attention directed toward prevention as well as the acute and chronic sequelae of these infections is needed.

Background We evaluated the impact of infectious disease (ID) syndromes on US active duty (AD) servicemembers returning from overseas deployment (DEP), military training exercises (EXR), or short-term military travel (eg, temporary assignment of duty [TDY]). Methods We conducted a survey-based assessment of US AD servicemembers returning from DEP, EXR, or TDY between 2015 and 2019. Subjects completed a post-travel survey capturing symptoms of travelers' diarrhea (TD), influenza-like illness (ILI), and febrile illness (FI). Risk factors associated with any ID syndrome (ie, either TD, ILI, or FI) that impacted daily activities were assessed using a logistic regression model with backward selection. Results One-third of servicemembers (654/1822) experienced an ID syndrome, and 26% (471/1822) reported a ≥50% reduction in activity level due to an ID syndrome (median duration, 3 days). TD was the most common ID syndrome experienced and accounted for 73% (346/471) of ID syndromes impacting daily activities. The greatest impact of ID syndromes was observed in servicemembers on DEP. Compared with servicemembers on EXR or TDY, those on DEP had a longer duration of travel and a delayed period of risk for ID syndromes. Multivariate analysis identified high-risk exposures (ie, environmental exposures, close contact with locals, consuming food from street vendors) and behaviors (ie, inability to sanitize hands before meals) that could be used to inform mitigation strategies. Conclusions ID syndromes result in a significant loss of productivity during military travel. Addressing modifiable risk factors and access to TD self-treatment in high-risk settings may help mitigate the impact of ID threats during military travel. [ABSTRACT FROM AUTHOR]

Background: Infection is a frequent and serious complication after combat-related trauma. The Sequential Organ Failure Assessment (SOFA) score has been shown to have predictive value for outcomes, including sepsis and mortality, among various populations. We evaluated the prognostic ability of SOFA score in a combat-related trauma population. Methods: Combat casualties (2009-2014) admitted to Landstuhl Regional Medical Center (LRMC; Germany) intensive care unit (ICU) within 4 days post-injury followed by transition to ICUs in military hospitals in the United States were included. Multivariate logistic regression was used to determine predictive effect of selected variables and receiver operating characteristic (ROC) curve analysis was used to evaluate overall accuracy of SOFA score for infection prediction. Results: Of the 748 patients who met inclusion criteria, 436 (58%) were diagnosed with an infection (32% bloodstream, 63% skin and soft tissue, and 40% pulmonary) and were predominantly young (median 24 years) males. Penetrating trauma accounted for 95% and 86% of injuries among those with and without infections, respectively (p < 0.001). Median LRMC admission SOFA score was 7 (interquartile range [IQR]: 4-9) in patients with infections versus 4 (IQR: 2-6) in patients without infections (p < 0.001). Thirty-day mortality was 2% in both groups. On multivariate regression, LRMC SOFA score was independently associated with infection development (odds ratio: 1.2; 95% confidence interval: 1.1-1.3). The ROC curve analysis revealed an area under the curve of 0.69 for infection prediction, and 0.80 for mortality prediction. Conclusions: The SOFA scores obtained up to 4 days post-injury predict late onset infection occurrence. This study revealed that for every 1 point increase in LRMC SOFA score, the odds of having an infection increases by a factor of 1.2, controlling for other predictors. The use of SOFA score in admission assessments may assist clinicians with identifying those at higher risk of infection following combat-related trauma. [ABSTRACT FROM AUTHOR]

Purpose: Individuals with methicillin-resistant Staphylococcus aureus (MRSA) skin and soft tissue infection (SSTI) can be simultaneously colonized with MRSA on multiple body sites. Using whole genome sequencing (WGS), the intrahost relatedness of MRSA colonization and infection isolates was investigated. Methods: In the context of a prospective case–control study of SSTI, we analyzed colonization and infection isolates from US Army Infantry trainees with purulent infection due to MRSA. At the time of clinical presentation for SSTI, culture swabs were obtained from the infection site, as well as from the patient's nasal, oral, inguinal, and perianal regions. S. aureus culture and susceptibility was performed by standard methods. DNA from MRSA isolates was extracted and libraries were produced. Sequences were generated on an Illumina MiSeq, sequence reads were assembled, and single nucleotide variant (SNV) data were analyzed. Results: Of 74 trainees with MRSA SSTI, 19 (25.7%) were colonized with MRSA. Ten (52.6%) were colonized on more than one body site. Colonization frequency by anatomic site was as follows: inguinal region (33%), nasal region (30%), perianal region (22%), and oral region (14%). A total of 36 MRSA colonization isolates were characterized. The intrahost median number of SNVs between infection and colonization isolates was 17. Among trainees with recurrent MRSA SSTI, limited intrahost diversity suggests that persistent colonization is a major contributor to recurrence risk. Conclusions: Among military trainees with MRSA SSTI, genomic characterization of infection and colonization isolates revealed a high degree of strain relatedness. Single acquisition events may account for MRSA colonization and infection in this population. [ABSTRACT FROM AUTHOR]

Background: The Trauma Infectious Disease Outcomes Study (TIDOS) cohort follows military personnel with deployment-related injuries in order to evaluate short- and long-term infectious complications. High rates of infectious complications have been observed in more than 30% of injured patients during initial hospitalization. We present data on infectious complications related to combat trauma after the initial period of hospitalization.Patients and Methods: Data related to patient care for military personnel injured during combat operations between June 2009 and May 2012 were collected. Follow-up data were captured from interviews with enrolled participants and review of electronic medical records.Results: Among 1,006 patients enrolled in the TIDOS cohort with follow-up data, 357 (35%) were diagnosed with one or more infection during their initial hospitalization, of whom 160 (45%) developed a trauma-related infection during follow-up (4.2 infections per 10,000 person-days). Patients with three or more infections during the initial hospitalization had a significantly higher rate of infections during the follow-up period compared with those with only one inpatient infection (incidence rate: 6.6 versus 3.1 per 10,000 days; p < 0.0001). There were 657 enrollees who did not have an infection during initial hospitalization, of whom 158 (24%) developed one during follow-up (incidence rate: 1.6 per 10,000 days). Overall, 318 (32%) enrolled patients developed an infection after hospital discharge (562 unique infections) with skin and soft-tissue infections being predominant (66%) followed by osteomyelitis (16%). Sustaining an amputation or open fracture, having an inpatient infection, and use of anti-pseudomonal penicillin (≥7 d) were independently associated with risk of an extremity wound infection during follow-up, whereas shorter hospitalization (15-30 d) was associated with a reduced risk.Conclusions: Combat-injured patients have a high burden of infectious complications that continue long after the initial period of hospitalization with soft-tissue and osteomyelitis being predominant. Further research on the long-term impact and outcomes of combat-associated infection is needed. [ABSTRACT FROM AUTHOR]

Background Infectious diarrhea is a common problem among travelers. Expert guidelines recommend the prompt use of antibiotics for self-treatment of moderate or severe travelers' diarrhea ( TD). There is limited data on whether travelers follow these self-treatment guidelines. We evaluated the risk factors associated with TD, the use of TD self-treatment, and the risk of irritable bowel syndrome ( IBS) during travel. Methods Department of Defense beneficiaries traveling outside the United States for ≤6.5 months were enrolled in a prospective cohort study. Participants received pre- and post-travel surveys, and could opt into a travel illness diary and follow-up surveys for symptoms of IBS. Standard definitions were used to assess for TD and IBS. Suboptimal self-treatment was defined as the use of antibiotics (with or without antidiarrheal agents) for mild TD, or the use of antidiarrheals alone or no self-treatment in cases of moderate or severe TD. Results Twenty-four percent of participants (270/1,120) met the criteria for TD. The highest incidence was recorded in Africa [8.6 cases/100 person-weeks, 95% confidence interval ( CI): 6.7-10.5]. Two hundred and twelve participants with TD provided information regarding severity and self-treatment: 89 (42%) had mild TD and 123 (58%) had moderate or severe TD. Moderate or severe TD was independently associated with suboptimal self-treatment [ OR 10.4 (95% CI: 4.92-22.0)]. Time to last unformed stool did not differ between optimal and suboptimal self-treatment. IBS occurred in 4.5% (7/154) of TD cases and in 3.1% (16/516) of cases without TD ( p = 0.39). Among TD cases, a lower incidence of IBS was noted in participants who took antibiotics [4.8% (5/105) vs 2.2% (1/46)] in those who did not, but the difference did not reach statistical significance ( p = 0.60). Conclusions Our results suggest the underutilization of antibiotics in travelers with moderate or severe TD. Further studies are needed to systematically evaluate pre-travel instruction and traveler adherence to self-treatment guidelines, and the impact of suboptimal self-treatment on outcomes. [ABSTRACT FROM AUTHOR]

The Infectious Diseases Clinical Research Program (IDCRP) at the Uniformed Services University of the Health Sciences (USU) is a National Institute of Allergy and Infectious Diseases (NIAID)-funded network of military treatment and research facilities coordinated through USU and the Henry M. Jackson Foundation for the Advancement of Military Medicine (HJF). IDCRP functions in collaboration with the NIAID, universities, and industry to address infectious diseases threats to the U.S. military and to the nation. Although IDCRP has projects in diseases from HIV to tuberculosis, a major focus has been on skin, soft-tissue, and war-related infections. [ABSTRACT FROM AUTHOR]

Background Recent work has argued that genus Klebsiella is best divided into 3 clades: K. pneumoniae (Kp) , K. quasipneumoniae (Kq), and K. variicola (Kv). Kv has drawn attention from reports of higher mortality and virulence. We evaluated a previously defined group of military trauma patients with Klebsiella infections for the presence of Kv, described clinical and isolate characteristics, and compared Kv and Kp groups. Methods All initial and serial (≥7 days from prior isolate) infecting Kp isolates (identified by clinical laboratories without the ability to speciate Kq and Kv) were collected from the Trauma Infectious Disease Outcomes Study (6/09–12/14). Additionally, a previously defined group of colonizing isolates linked to the infecting isolates and a selection of random colonizers were included from groin swabs. DNA extraction and PCR targeting Kv per published methods was performed. Antimicrobial susceptibilities were determined using the BD Phoenix Automated Microbiology System and CLSI criteria. Multidrug resistance was defined as either resistance to ≥3 classes of aminoglycosides, β-lactams, carbapenems and/or fluoroquinolones or production of ESBL or KPC. Results Of 237 archived Kp isolates (from 122 patients), 10 (4%) were identified as Kv by PCR (from 8 [7%] patients). The Kv sources were 4 from blood (40%), 1 intra-abdominal (10%) and 5 from groin (50%). Six (3%) isolates were identified as Kq (4 from groin and 2 from respiratory specimens). The Kv and Kp patients were all males, with a median age of 25 (IQR 21–46) and 23 (IQR 21–28), length of hospital stay of 24 days (IQR: 5–106) and 53 days (IQR 36–74), and Injury Severity Score of 21 (IQR: 10–50) and 38 (IQR: 30–45), respectively. There were no deaths in the Kv group compared with 4 with Kp. Infecting Kv isolates were more likely to be from blood compared with Kp (80% vs. 17%, P = 0.04). No infecting Kv isolates were multidrug-resistant compared with 70% of infecting Kp isolates (P < 0.01). Conclusion Kv represented 4% of the previously identified Kp isolates in this population. Patient characteristics were similar in both groups. While Kv was less resistant than Kp, it was more likely to be associated with invasive disease in this group. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

Introduction Military trainees are at increased risk for infectious disease outbreaks because of the unique circumstances of the training environment (e.g. close proximity areas and physiologic/psychologic stress). Standard medical countermeasures in military training settings include routine immunization (e.g. influenza and adenovirus) as well as chemoprophylaxis [e.g. benzathine penicillin G (Bicillin) for the prevention of group A streptococcal disease] for pathogens associated with outbreaks in these settings. In a population of U.S. Army Infantry trainees, we evaluated changes in the oral microbiome during a 14-week military training cycle. Materials and Methods Trainees were enrolled in an observational cohort study in 2015–2016. In 2015, Bicillin was administered to trainees to ameliorate the risk of group A Streptococcus outbreaks, whereas in 2016, trainees did not receive a Bicillin inoculation. Oropharyngeal swabs were collected from participants at days 0, 7, 14, 28, 56, and 90 of training. Swabs were collected, flash frozen, and stored. DNA was extracted from swabs, and amplicon sequencing of the 16s rRNA gene was performed. Microbiome dynamics were evaluated using the QIIME 2 workflow along with DADA2, SINA with SILVA, and an additional processing in R. Results We observed that microbiome samples from the baseline (day 0) visit were distinct from one another, whereas samples collected on day 14 exhibited significant microbiome convergence. Day 14 convergence was coincident with an increase in DNA sequences associated with Streptococcus , though there was not a significant difference between Streptococcus abundance over time between 2015 and 2016 (P  = .07), suggesting that Bicillin prophylaxis did not significantly impact overall Streptococcus abundance. Conclusions The temporary convergence of microbiomes is coincident with a rise in communicable infections in this population. The dynamic response of microbiomes during initial military training supports similar observations in the literature of transient convergence of the human microbiome under cohabitation in the time frame including in this experiment. This population and the associated longitudinal studies allow for controlled studies of human microbiome under diverse conditions. [ABSTRACT FROM AUTHOR]

Background Biocides play an integral role in infection control. Paralleling concern about rising incidence of multidrug-resistant (MDR) organisms is a concern for resistance to biocides. In small studies, several genes involved in the production of efflux pump proteins have been identified as markers of biocide resistance in Klebsiella spp. namely cepA , qacA , qacE , qac∆E , and acrA. This study aimed to analyze the Klebsiella spp. isolates of a previously defined military trauma group with a high incidence of MDR organisms for the presence of these genes and their correlation with other resistance. Methods All infecting K. pneumoniae, K. variicola , and K. quasipneumoniae isolates archived by the Trauma Infectious Disease Outcomes Study (June 2009–December 2014) were selected. Additionally, all colonizing isolates linked with infecting isolates were included; the remainder to total 50 MDR and 46 non-MDR colonizing isolates were chosen randomly. Antimicrobial identification and susceptibilities were determined by CLSI criteria using the BD Phoenix Automated Microbiology System. PCR according to published methods for cepA , qacA , qacE , qac∆E , and acrA was accomplished in duplicate. MDR was defined as either resistance to ≥3 classes of aminoglycosides, β-lactams, carbapenems and/or fluoroquinolones or production of an ESBL or KPC. Results A total of 237 isolates (221 K. pneumoniae , 10 K. variicola , 6 K. quasipneumoniae) met inclusion criteria, of which 149 (63%) were MDR. All isolates had been exposed to antimicrobials prior to isolation. Of all isolates, 234 (98%) carried cepA : 218 (98%) K. pneumoniae carried cepA, 10 (100%) K. variicola carried cepA, and 6 (100%) of K. quasipneumoniae carried cepA. In addition, 148 (62%) isolates with cepA were MDR. One (10%) K. variicola isolate carried qacE along with cepA. This isolate was the only MDR K. variicola. None of the isolates carried qacA, qac∆E, or acrA. Conclusion We confirmed the near universal presence of the cepA biocide resistance gene in Klebsiella spp. isolated from trauma patients in Iraq and Afghanistan. In the largest evaluation of biocide resistance genes in Klebsiella spp. to our knowledge, the presence of qacA , qacE , qac∆E , and acrA was less common than has been reported elsewhere. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

Background: Infectious diseases pose a significant threat to health and readiness of military personnel deployed globally during wartime and peacekeeping activities. Surveillance and improvement in mitigation through research of infectious disease threats remain an integral part of Force Health Protection. Herein, we review research efforts of the Infectious Disease Clinical Research Program related to deployment and travel-related infections.Methods: The objectives of the Deployment and Travel-Related Infections Research Area are to (1) provide epidemiologic and clinical data, including pathogen-specific estimates of disease incidence among deployed troops, (2) execute clinical trials and effectiveness studies to improve recommendations regarding prevention and treatment of infections during deployment, and (3) evaluate the knowledge and practice patterns of health care providers engaged in deployment/travel medicine and the impact on outcomes. The centerpiece protocol of the research area is the Deployment and Travel-Related Infectious Disease Risk Assessment, Outcomes, and Prevention Strategies cohort study (TravMil), which was initiated in 2010 and collects data on a broad range of deployment-related infections.Results: To date, 4,154 deployed military personnel and traveling Department of Defense (DoD) beneficiaries have been enrolled in TravMil. Surveillance data collected through the TravMil study provide assessment of deployment and travel-related infectious disease threats, and the effectiveness of mitigation strategies. The incidence of travelers' diarrhea, influenza-like illness, and undifferentiated febrile illness is 20.48%, 9.34%, and 6.16%, respectively. The cohort study also provides necessary infrastructure to execute clinical trials. The TrEAT TD clinical trial evaluated the effectiveness of single-dose antibiotic therapy for travelers' diarrhea in the deployed setting. When compared to levofloxacin, azithromycin was not inferior; however, inferiority was not demonstrated with use of single dose of rifaximin. The trial findings supported the development of a deployment-related health guideline for the management of acute diarrheal disease. A clinical trial evaluating the effectiveness of rifaximin for prevention for travelers' diarrhea (Prevent TD) is underway.Conclusions: The research area has proven its ability to conduct impactful research, including the development of field-expedient diagnostics, the largest DoD multi-site travelers' diarrhea randomized control trial in peacetime and combat settings, and informed Force Health Protection guidance. The research area continues to provide surveillance data to military commands via an established collaborative network of military treatment facilities, DoD laboratories (both within and outside the continental United States), foreign militaries, and academia. The conduct of clinical and translational research in a deployment setting presents significant challenges, most notably in recruitment/enrollment and compliance with study-related procedures during deployment. [ABSTRACT FROM AUTHOR]

We present extremity wound microbiology data from 250 combat casualties (2009–2012). Confirmed extremity wound infections (EWIs) were based on clinical and laboratory findings. Suspected EWIs had isolation of organisms from wound cultures with associated signs/symptoms not meeting clinical diagnostic criteria. Colonized wounds had organisms isolated without any infection suspicion. A total of 335 confirmed EWIs (131 monomicrobial and 204 polymicrobial) were assessed. Gram-negative bacteria were predominant (57% and 86% of monomicrobial and polymicrobial infections, respectively). In polymicrobial infections, 61% grew only bacteria, while 30% isolated bacteria and mold. Multidrug resistance was observed in 32% of isolates from first monomicrobial EWIs ±3 days of diagnosis, while it was 44% of isolates from polymicrobial EWIs. Approximately 96% and 52% of the suspected and colonized wounds, respectively, shared ≥1 organism in common with the confirmed EWI on the same patient. Understanding of combat-related EWIs can lead to improvements in combat casualty care. • Sixty-one percent of 335 confirmed extremity wound infections were polymicrobial. • Gram-negative bacteria predominant among combat-related extremity wound infections. • Enterococcus spp. most frequent organism isolated from polymicrobial infections. [ABSTRACT FROM AUTHOR]

Background: During the conflicts in Iraq and Afghanistan, more than 52,000 U.S. military members were wounded in action. The battlefield mortality rate was lower than in past conflicts, however, those surviving often had complex soft tissue and bone injuries requiring multiple surgeries. This report describes the rates, types, and risks of infections complicating the care of combat casualties.Patients and Methods: Infection and microbiology data obtained from the Trauma Infectious Disease Outcomes Study (TIDOS), a prospective observational study of infections complicating deployment-related injuries, were used to determine the proportion of infection, types, and associated organisms. Injury and surgical information were collected from the Department of Defense Trauma Registry. Multivariable Cox proportional hazards and logistic regression models were used to evaluate potential factors associated with infection.Results: From 2009-2012, 1,807 combat casualties were evacuated to U.S. TIDOS-participating hospitals. Among the 1,807 patients, the proportion of overall infections from time of injury through initial U.S. hospitalization was 34% with half being skin, soft tissue, or bone infections. Infected wounds most commonly grew Enterococcus faecium, Pseudomonas aeruginosa, Acinetobacter spp. or Escherichia coli. In the multivariable model, amputation, blood transfusions, intensive care unit admission, injury severity scores, mechanical ventilation, and mechanism of injury were associated with risk of infection.Conclusions: One-third of combat casualties from Iraq and Afghanistan develop infections during their initial hospitalization. Amputations, blood transfusions, and overall injury severity are associated with risk of infection, whereas more easily modifiable factors such as early operative intervention or antibiotic administration are not. [ABSTRACT FROM AUTHOR]

Background: The contribution of multi-drug-resistant gram-negative bacilli infections (MDRGN-I) in patients with trauma is not well described. We present characteristics of MDRGN-Is among military personnel with deployment-related trauma (2009-2014).Patients and Methods: Data from the Trauma Infectious Disease Outcomes Study were assessed for infectious outcomes and microbial recovery. Infections were classified using standardized definitions. Gram-negative bacilli were defined as multi-drug-resistant if they showed resistance to ≥3 antibiotic classes or were producers of extended-spectrum β-lactamase or carbapenemases.Results: Among 2,699 patients admitted to participating U.S. hospitals, 913 (33.8%) experienced ≥1 infection event, of which 245 (26.8%) had a MDRGN-I. There were 543 MDRGN-I events (24.6% of unique 2,210 infections) with Escherichia coli (48.3%), Acinetobacter spp. (38.6%), and Klebsiella pneumoniae (8.4%) as the most common MDRGN isolates. Incidence of MDRGN-I was 9.1% (95% confidence interval [CI]: 8.0-10.2). Median time to MDRGN-I event was seven days with 75% occurring within 13 days post-trauma. Patients with MDRGN-Is had a greater proportion of blast injuries (84.1% vs. 62.5%; p < 0.0001), traumatic amputations (57.5% vs. 16.3%; p < 0.0001), and higher injury severity (82.0% had injury severity score ≥25 vs. 33.7%; p < 0.0001) compared with patients with either no infections or non-MDRGN-Is. Furthermore, MDRGN-I patients were more frequently admitted to the intensive care unit (90.5% vs. 48.5%; p < 0.0001), colonized with a MDRGN before infection (58.0% vs. 14.7%; p < 0.0001), and required mechanical ventilation (78.0% vs. 28.8% p < 0.0001). Antibiotic exposure before the MDRGN-I event was significantly higher across antibiotic classes except first generation cephalosporins and tetracyclines, which were very commonly used with all patients. Regarding outcomes, patients with MDRGN-Is had a longer length of hospitalization than the comparator group (53 vs. 18 days; p < 0.0001).Conclusions: We found a high rate of MDRGN-I in our population characterized by longer hospitalization and greater injury severity. These findings inform treatment and infection control decisions in the trauma patient population. [ABSTRACT FROM AUTHOR]