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Background: Infections are the most frequent complication and cause of mortality in burn patients. We describe the epidemiology and outcomes of infections among deployed U.S. military personnel with burns., Methods: Military personnel who sustained a burn injury in Iraq or Afghanistan (2009-2014) and were admitted to the Burn Center at U.S. Army Institute of Surgical Research at Brooke Army Medical Center were included in the analysis., Results: The study population included 144 patients who were primarily young (median 24 years) males (99 %) with combat-related burns (62 %) sustained via a blast (57 %), resulting in a median total body surface area burned (TBSA) of 6 % (IQR 3-14 %). Twenty-six (18 %) patients developed infections, with pneumonia being the predominant initial infection (= 16), followed by skin and soft-tissue infections (SSTI, = 6), bloodstream infections (BSI, = 3), and intra-abdominal infections (IAI, = 1). Initial infections were diagnosed at a median of 4 days (IQR 3-5) post-injury for pneumonia, 7 days (IQR 4-12) for SSTIs, 7 days (IQR 6-7) for BSI, and 17 days for IAI. Patients with infections were more severely injured with greater TBSA (median 31 % vs 5 %), more inhalation injury (38 % vs 12 %), and longer time to definitive surgical management (median of 34 days vs 9) compared to those who did not develop infections (p < 0.001). Among patients with inhalation injury, a higher proportion developed pneumonia (42 %) compared to those without inhalation injury (5 %; p < 0.001). Five patients developed an invasive fungal infection. Gram-negative bacilli were most frequently recovered, with 32 % of Gram-negative isolates being multidrug-resistant. Four patients died, of whom all had ≥ 4 infections., Conclusions: Military personnel with burn injuries who developed infections were more severely injured with greater TBSA and inhalation injury. Improved understanding of risk factors for burn-related infections in combat casualties is critical for effective management., Competing Interests: Declaration of Competing Interest The authors have no conflicts to disclose. All authors approved the final version for submission., (Published by Elsevier Ltd.)

Introduction: Battlefield-related wound infections are a significant source of morbidity among combat casualties. Seasonality of these infections was demonstrated in previous conflicts (e.g., Korea) but has not been described with trauma-related health care-associated infections from the war in Afghanistan., Methods: The study population included military personnel wounded in Afghanistan (2009-2014) medevac'd to Landstuhl Regional Medical Center and transitioned to participating military hospitals in the United States with clinical suspicion of wound infections and wound cultures collected ≤7 days post-injury. Analysis was limited to the first wound culture from individuals. Infecting isolates were collected from skin and soft-tissue infections, osteomyelitis, and burn soft-tissue infections. Data were analyzed by season (winter [ December 1-February 28/29], spring [March 1-May 31], summer [June 1-August 31], and fall [September 1-November 30])., Results: Among 316 patients, 297 (94.0%) sustained blast injuries with a median injury severity score and days from injury to initial culture of 33 and 3.5, respectively. Although all patients had a clinical suspicion of a wound infection, a diagnosis was confirmed in 198 (63%) patients. Gram-negative bacilli (59.5% of 316) were more commonly isolated from wound cultures in summer (68.1%) and fall (67.1%) versus winter (43.9%) and spring (45.1%; P < .001). Multidrug-resistant (MDR) Gram-negative bacilli (21.8%) were more common in summer (21.8%) and fall (30.6%) versus winter (7.3%) and spring (19.7%; P = .028). Findings were similar for infecting Gram-negative bacilli (72.7% of 198)-summer (79.5%) and fall (83.6%; P = .001)-and infecting MDR Gram-negative bacilli (27.3% of 198)-summer (25.6%) and fall (41.8%; P = .015). Infecting anaerobes were more common in winter (40%) compared to fall (11%; P = .036). Gram-positive organisms were not significantly different by season., Conclusion: Gram-negative bacilli, including infecting MDR Gram-negative bacilli, were more commonly recovered in summer/fall months from service members injured in Afghanistan. This may have implications for empiric antibiotic coverage during these months., (Published by Oxford University Press on behalf of the Association of Military Surgeons of the United States 2023. 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 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.)

Recent reclassification of the Klebsiella genus to include Klebsiella variicola, and its association with bacteremia and mortality, has raised concerns. We examined Klebsiella spp. infections among battlefield trauma patients, including occurrence of invasive K. variicola disease. Klebsiella isolates collected from 51 wounded military personnel (2009-2014) through the Trauma Infectious Disease Outcomes Study were examined using polymerase chain reaction (PCR) and pulsed-field gel electrophoresis. K. variicola isolates were evaluated for hypermucoviscosity phenotype by the string test. Patients were severely injured, largely from blast injuries, and all received antibiotics prior to Klebsiella isolation. Multidrug-resistant Klebsiella isolates were identified in 23 (45%) patients; however, there were no significant differences when patients with and without multidrug-resistant Klebsiella were compared. A total of 237 isolates initially identified as K. pneumoniae were analyzed, with 141 clinical isolates associated with infections (remaining were colonizing isolates collected through surveillance groin swabs). Using PCR sequencing, 221 (93%) isolates were confirmed as K. pneumoniae, 10 (4%) were K. variicola, and 6 (3%) were K. quasipneumoniae. Five K. variicola isolates were associated with infections. Compared to K. pneumoniae, infecting K. variicola isolates were more likely to be from blood (4/5 versus 24/134, p = 0.04), and less likely to be multidrug-resistant (0/5 versus 99/134, p<0.01). No K. variicola isolates demonstrated the hypermucoviscosity phenotype. Although K. variicola isolates were frequently isolated from bloodstream infections, they were less likely to be multidrug-resistant. Further work is needed to facilitate diagnosis of K. variicola and clarify its clinical significance in larger prospective studies., Competing Interests: KM, SJK, MLC, and DL are employees of the Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc. (HJF), a not-for-profit Foundation authorized by Congress to support research at the Uniformed Services University of the Health Sciences (USU) and throughout military medicine. This does not alter our adherence to PLOS ONE policies on sharing data and materials. Please see Data Availability Statement.

Introduction: We examined antibiotic management of combat-related extremity wound infections (CEWI) among wounded U.S. military personnel (2009-2012)., Methods: Patients were included if they sustained blast injuries, resulting in ≥1 open extremity wound, were admitted to participating U.S. hospitals, developed a CEWI (osteomyelitis or deep soft-tissue infections) within 30 days post-injury, and received ≥3 days of relevant antibiotic (s) for treatment., Results: Among 267 patients, 133 (50%) had only a CEWI, while 134 (50%) had a CEWI plus concomitant non-extremity infection. In the pre-diagnosis period (4-10 days prior to CEWI diagnosis), 95 (36%) patients started a new antibiotic with 28% of patients receiving ≥2 antibiotics. During CEWI diagnosis week (±3 days of diagnosis), 209 (78%) patients started a new antibiotic (71% with ≥2 antibiotics). In the week following diagnosis (4-10 days after CEWI diagnosis), 121 (45%) patients started a new antibiotic with 39% receiving ≥2 antibiotics. Restricting to ±7 days of CEWI diagnosis, patients commonly received two (35%) or three (27%) antibiotics with frequent combinations involving carbapenem, vancomycin, and fluoroquinolones., Conclusions: Substantial variation in antibiotic prescribing patterns related to CEWIs warrants development of combat-related clinical practice guidelines beyond infection prevention, to include strategies to reduce the use of unnecessary antibiotics and improve stewardship., (Published by Oxford University Press on behalf of Association of Military Surgeons of the United States 2020.)

Trauma-related invasive fungal wound infections (IFIs) are associated with significant morbidity and mortality. Early identification and treatment are critical. Traditional identification methods (e.g., fungal cultures and histopathology) can be delayed and insensitive. We assessed a PCR-based sequencing assay for rapid identification of filamentous fungi in formalin-fixed paraffin-embedded (FFPE) specimens obtained from combat casualties injured in Afghanistan. Blinded FFPE specimens from cases (specimens positive on histopathology) and controls (specimens negative on histopathology) were submitted for evaluation with a panfungal PCR. The internal transcribed spacer 2 (ITS2) region of the fungal ribosomal repeat was amplified and sequenced. The PCR results were compared with findings from histopathology and/or culture. If injury sites contributed multiple specimens, findings for the site were collapsed to the site level. We included 64 case subjects (contributing 95 sites) and 102 controls (contributing 118 sites). Compared to histopathology, panfungal PCR was specific (99%), but not as sensitive (63%); however, sensitivity improved to 83% in specimens from sites with angioinvasion. Panfungal PCR identified fungi of the order Mucorales in 33 of 44 sites with angioinvasion (75%), whereas fungal culture was positive in 20 of 44 sites (45%). Saksenaea spp. were the dominant fungi identified by PCR in specimens from angioinvasion sites (57%). Panfungal PCR is specific, albeit with lower sensitivity, and performs better at identifying fungi of the order Mucorales than culture. DNA sequencing offers significant promise for the rapid identification of fungal infection in trauma-related injuries, leading to more timely and accurate diagnoses., (Copyright © 2019 American Society for Microbiology.)

To evaluate a classification system to support clinical decisions for treatment of contaminated deep wounds at risk for an invasive fungal infection (IFI), we studied 246 US service members (413 wounds) injured in Afghanistan (2009-2014) who had laboratory evidence of fungal infection. A total of 143 wounds with persistent necrosis and laboratory evidence were classified as IFI; 120 wounds not meeting IFI criteria were classified as high suspicion (patients had localized infection signs/symptoms and had received antifungal medication for >10 days), and 150 were classified as low suspicion (failed to meet these criteria). IFI patients received more blood than other patients and had more severe injuries than patients in the low-suspicion group. Fungi of the order Mucorales were more frequently isolated from IFI (39%) and high-suspicion (21%) wounds than from low-suspicion (9%) wounds. Wounds that did not require immediate antifungal therapy lacked necrosis and localized signs/symptoms of infection and contained fungi from orders other than Mucorales.

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., (Copyright © 2019 Elsevier Inc. All rights reserved.)

We examined risk factors for combat-related extremity wound infections (CEWI) among U.S. military patients injured in Iraq and Afghanistan (2009-2012). Patients with ≥1 combat-related, open extremity wound admitted to a participating U.S. hospital (≤7 days postinjury) were retrospectively assessed. The population was classified based upon most severe injury (amputation, open fracture without amputation, or open soft-tissue injury defined as non-fracture/non-amputation wounds). Among 1271 eligible patients, 395 (31%) patients had ≥1 amputation, 457 (36%) had open fractures, and 419 (33%) had open soft-tissue wounds as their most severe injury, respectively. Among patients with traumatic amputations, 100 (47%) developed a CEWI compared to 66 (14%) and 12 (3%) patients with open fractures and open soft-tissue wounds, respectively. In a Cox proportional hazard analysis restricted to CEWIs ≤30 days postinjury among the traumatic amputation and open fracture groups, sustaining an amputation (hazard ratio: 1.79; 95% confidence interval: 1.25-2.56), blood transfusion ≤24 hours postinjury, improvised explosive device blast, first documented shock index ≥0.80, and >4 injury sites were independently associated with CEWI risk. The presence of a non-extremity infection at least 4 days prior to a CEWI diagnosis was associated with lower CEWI risk, suggesting impact of recent exposure to directed antimicrobial therapy. Further assessment of early clinical management will help to elucidate risk factor contribution. The wound classification system provides a comprehensive approach in assessment of injury and clinical factors for the risk and outcomes of an extremity wound infection., (Published by Oxford University Press on behalf of the Association of Military Surgeons of the United States 2019.)

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.

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.

Background: Combat-related extremity wound infections can complicate the recovery of injured military personnel. The Enterococcus genus contains both commensal and pathogenic bacteria found in many combat wounds. We describe the patient population susceptible to Enterococcus infection, the characteristics of Enterococcus spp. isolated from combat-related wounds, and the microbiological profile of Enterococcus-positive wounds., Methods: Patient and culture data were obtained from the Trauma Infectious Disease Outcomes Study. Subjects were divided into a case group with enterococcal extremity wound infections and a comparator group with wound infections caused by other micro-organisms., Results: Case and comparator subjects had similar patterns of injury and infection. Case subjects had higher Injury Severity Scores (33 vs. 30; p < 0.001), longer hospitalization at U.S. facilities (55 vs. 40 days; p = 0.004), and required more large-volume blood transfusions (>20 units) within 24 h post-injury (53% vs. 30%; p < 0.001). Approximately 60% of case subjects had three or more infections, and 91% had one or more polymicrobial infections, compared with 43% and 50%, respectively, in the comparator group. The thigh was the most common site of Enterococcus spp. isolation, contributing 50% of isolates. Enterococcus faecium was the predominant species isolated from case-group infections overall (66%), as well as in polymicrobial infections (74%). Frequent co-colonizing microbes in polymicrobial wound infections with Enterococcus were other ESKAPE pathogens (64%) (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae [and Escherichia coli], Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp.) and fungi (35%)., Conclusions: The specific pathogenicity of Enterococcus relative to other pathogens in polymicrobial wounds is unknown. Identifying strain-specific outcomes and investigating the interactions of Enterococcus strains with other wound pathogens could provide additional tools and strategies for infection mitigation in combat-related wounds.

The Trauma Infectious Disease Outcomes Study began in June 2009 as combat operations were decreasing in Iraq and increasing in Afghanistan. Our analysis examines the rate of infections of wounded U.S. military personnel from operational theaters in Iraq and Afghanistan admitted to Landstuhl Regional Medical Center between June 2009 and December 2013 and transferred to a participating U.S. hospital. Infection risk factors were examined in a multivariate logistic regression analysis (expressed as odds ratios [OR]; 95% confidence intervals [CI]). The study population includes 524 wounded military personnel from Iraq and 4,766 from Afghanistan. The proportion of patients with at least one infection was 28% and 34% from the Iraq and Afghanistan theaters, respectively. The incidence density rate was 2.0 (per 100 person-days) for Iraq and 2.7 infections for Afghanistan. Independent risk factors included large-volume blood product transfusions (OR: 10.68; CI: 6.73-16.95), high Injury Severity Score (OR: 2.48; CI: 1.81-3.41), and improvised explosive device injury mechanism (OR: 1.84; CI: 1.35-2.49). Operational theater (OR: 1.32; CI: 0.87-1.99) was not a risk factor. The difference in infection rates between operational theaters is primarily a result of increased injury severity in Afghanistan from a higher proportion of blast-related trauma during the study period., (Reprint & Copyright © 2016 Association of Military Surgeons of the U.S.)

Background: Tranexamic acid (TXA) has been shown to reduce mortality from severe haemorrhage. Although recent data suggest that TXA has anti-inflammatory properties, few analyses have investigated the impact of TXA on infectious complications in injured patients. The aim was to examine the association between TXA administration and infection risk among injured military personnel., Methods: Patients who received TXA were matched by Injury Severity Score with patients who did not receive TXA. Conditional logistic regression was used to examine risk factors associated with infections within 30 days. A Cox proportional analysis evaluated risk factors in a time-to-first-infection model., Results: A total of 335 TXA recipients were matched with 626 patients who did not receive TXA. A greater proportion of TXA recipients had an infection compared with the comparator group (P < 0·001). Univariable analysis estimated an unadjusted odds ratio (OR) of 2·47 (95 per cent c.i. 1·81 to 3·36) for the association between TXA and infection risk; however, TXA administration was not significant in multivariable analysis (OR 1·27, 0·85 to 1·91). Blast injuries, intensive care unit (ICU) admission, and receipt of 10 units or more of blood within 24 h after injury were independently associated with infection risk. The Cox proportional model confirmed the association with ICU admission and blood transfusion. Traumatic amputations were also significantly associated with a reduced time to first infection., Conclusion: In life-threatening military injuries matched for injury severity, TXA recipients did not have a higher risk of having infections nor was the time to develop infections shorter than in non-recipients. Extent of blood loss, blast injuries, extremity amputations and ICU stay were associated with infection., (© 2016 BJS Society Ltd Published by John Wiley & Sons Ltd.)

Data from recent conflicts related to war wounds and obligate anaerobes are limited. We define the epidemiology and antimicrobial susceptibility of obligate anaerobes from Iraq and Afghanistan casualties (6/2009-12/2013), as well as their association with clinical outcomes. Susceptibility against eleven antibiotics (7 classes) was tested. Overall, 59 patients had 119 obligate anaerobes identified (83 were first isolates). Obligate anaerobes were isolated 7-13 days post-injury, primarily from lower extremity wounds (43%), and were largely Bacteroides spp. (42%) and Clostridium spp. (19%). Patients with pelvic wounds were more likely to have Bacteroides spp. and concomitant resistant gram-negative aerobes. Seventy-three percent of isolates were resistant to ≥1 antimicrobials. Bacteroides spp. demonstrated the most resistance (16% of first isolates). Patients with resistant isolates had similar outcomes to those with susceptible strains. Serial recovery of isolates occurred in 15% of patients and was significantly associated with isolation of Bacteroides spp., along with resistant gram-negative aerobes., (Published by Elsevier Inc.)

During the recent war in Afghanistan (2001-2014), invasive fungal wound infections (IFIs) among US combat casualties were associated with risk factors related to the mechanism and pattern of injury. Although previous studies recognized that IFI patients primarily sustained injuries in southern Afghanistan, environmental data were not examined. We compared environmental conditions of this region with those of an area in eastern Afghanistan that was not associated with observed IFIs after injury. A larger proportion of personnel injured in the south (61%) grew mold from wound cultures than those injured in the east (20%). In a multivariable analysis, the southern location, characterized by lower elevation, warmer temperatures, and greater isothermality, was independently associated with mold contamination of wounds. These environmental characteristics, along with known risk factors related to injury characteristics, may be useful in modeling the risk for IFIs after traumatic injury in other regions.

Combat trauma wounds with invasive fungal infections (IFIs) are often polymicrobial with fungal and bacterial growth, but the impact of the wound microbiology on clinical outcomes is uncertain. Our objectives were to compare the microbiological features between IFI and non-IFI wounds and evaluate whether clinical outcomes differed among IFI wounds based upon mold type. Data from U.S. military personnel injured in Afghanistan with IFI wounds were examined. Controls were matched by the pattern/severity of injury, including blood transfusion requirements. Wound closure timing was compared between IFI and non-IFI control wounds (with/without bacterial infections). IFI wound closure was also assessed according to mold species isolation. Eighty-two IFI wounds and 136 non-IFI wounds (63 with skin and soft tissue infections [SSTIs] and 73 without) were examined. The time to wound closure was longer for the IFI wounds (median, 16 days) than for the non-IFI controls with/without SSTIs (medians, 12 and 9 days, respectively; P < 0.001). The growth of multidrug-resistant Gram-negative rods was reported among 35% and 41% of the IFI and non-IFI wounds with SSTIs, respectively. Among the IFI wounds, times to wound closure were significantly longer for wounds with Mucorales growth than for wounds with non-Mucorales growth (median, 17 days versus 13 days; P < 0.01). When wounds with Mucorales and Aspergillus spp. growth were compared, there was no significant difference in wound closure timing. Trauma wounds with SSTIs were often polymicrobial, yet the presence of invasive molds (predominant types: order Mucorales, Aspergillus spp., and Fusarium spp.) significantly prolonged the time to wound closure. Overall, the times to wound closure were longest for the IFI wounds with Mucorales growth., (Copyright © 2015, American Society for Microbiology. All Rights Reserved.)

The emergence of invasive fungal wound infections (IFIs) in combat casualties led to development of a combat trauma-specific IFI case definition and classification. Prospective data were collected from 1133 US military personnel injured in Afghanistan (June 2009-August 2011). The IFI rates ranged from 0·2% to 11·7% among ward and intensive care unit admissions, respectively (6·8% overall). Seventy-seven IFI cases were classified as proven/probable (n = 54) and possible/unclassifiable (n = 23) and compared in a case-case analysis. There was no difference in clinical characteristics between the proven/probable and possible/unclassifiable cases. Possible IFI cases had shorter time to diagnosis (P = 0·02) and initiation of antifungal therapy (P = 0·05) and fewer operative visits (P = 0·002) compared to proven/probable cases, but clinical outcomes were similar between the groups. Although the trauma-related IFI classification scheme did not provide prognostic information, it is an effective tool for clinical and epidemiological surveillance and research.

Background: Complex traumatic injuries sustained by military personnel, particularly when involving extremities, often result in infectious complications and substantial morbidity. One factor that may further impair patient recovery is the persistence of infections. Surface-attached microbial communities, known as biofilms, may play a role in hindering the management of infections; however, clinical data associating biofilm formation with persistent or chronic infections are lacking. Therefore, we evaluated the production of bacterial biofilms as a potential risk factor for persistent infections among wounded military personnel., Methods: Bacterial isolates and clinical data from military personnel with deployment-related injuries were collected through the Trauma Infectious Disease Outcomes Study. The study population consisted of patients with diagnosed skin and soft-tissue infections. Cases (wounds with bacterial isolates of the same organism collected 14 days apart) were compared to controls (wounds with non-recurrent bacterial isolates), which were matched by organism and infectious disease syndrome. Potential risk factors for persistent infections, including biofilm formation, were examined in a univariate analysis. Data are expressed as odds ratios (OR; 95% confidence interval [CI])., Results: On a per infected wound basis, 35 cases (representing 25 patients) and 69 controls (representing 60 patients) were identified. Eight patients with multiple wounds were utilized as both cases and controls. Overall, 235 bacterial isolates were tested for biofilm formation in the case-control analysis. Biofilm formation was significantly associated with infection persistence (OR: 29.49; CI: 6.24-infinity) in a univariate analysis. Multidrug resistance (OR: 5.62; CI: 1.02-56.92), packed red blood cell transfusion requirements within the first 24 hours (OR: 1.02; CI: 1.01-1.04), operating room visits prior to and on the date of infection diagnosis (OR: 2.05; CI: 1.09-4.28), anatomical location of infected wound (OR: 5.47; CI: 1.65-23.39), and occurrence of polymicrobial infections (OR: 69.71; CI: 15.39-infinity) were also significant risk factors for persistent infections., Conclusions: We found that biofilm production by clinical strains is significantly associated with the persistence of wound infections. However, the statistical power of the analysis was limited due to the small sample size, precluding a multivariate analysis. Further data are needed to confirm biofilm formation as a risk factor for persistent wound infections.

In 2008, a clinical practice guideline (CPG) was developed for the prevention of infections among military personnel with combat-related injuries. Our analysis expands on a prior 6-month evaluation and assesses CPG adherence with respect to antimicrobial prophylaxis for U.S. combat casualties medically evacuated to Landstuhl Regional Medical Center over a 1-year period (June 2009 through May 2010), with an eventual goal of continuously monitoring CPG adherence and measuring outcomes as a function of compliance. We classified adherence to the CPG as receipt of recommended antimicrobials within 48 hours of injury. A total of 1106 military personnel eligible for CPG assessment were identified and 74% received antimicrobial prophylaxis. Overall, CPG compliance within 48 hours of injury was 75%. Lack of antimicrobial prophylaxis contributed 2 to 22% to noncompliance varying by injury category, whereas receipt of antibiotics other than preferred was 11 to 30%. For extremity injuries, antimicrobial prophylaxis adherence was 60 to 83%, whereas it was 80% for closed injuries and 68% for penetrating abdominal injuries. Overall, the results of our analysis suggest an ongoing need to improve adherence, monitor CPG compliance, and assess effectiveness., (Reprint & Copyright © 2014 Association of Military Surgeons of the U.S.)

Background: Major advances in combat casualty care have led to increased survival of patients with complex extremity trauma. Invasive fungal wound infections (IFIs) are an uncommon, but increasingly recognized, complication following trauma that require greater understanding of risk factors and clinical findings to reduce morbidity., Methods: The patient population includes US military personnel injured during combat from June 2009 through December 2010. Case definition required wound necrosis on successive debridements with IFI evidence by histopathology and/or microbiology (Candida spp excluded). Case finding and data collected through the Trauma Infectious Disease Outcomes Study utilized trauma registry, hospital records or operative reports, and pathologist review of histopathology specimens., Results: A total of 37 cases were identified: proven (angioinvasion, n=20), probable (nonvascular tissue invasion, n=4), and possible (positive fungal culture without histopathological evidence, n=13). In the last quarter surveyed, rates reached 3.5% of trauma admissions. Common findings include blast injury (100%) during foot patrol (92%) occurring in southern Afghanistan (94%) with lower extremity amputation (80%) and large volume blood transfusion (97.2%). Mold isolates were recovered in 83% of cases (order Mucorales, n=16; Aspergillus spp, n=16; Fusarium spp, n=9), commonly with multiple mold species among infected wounds (28%). Clinical outcomes included 3 related deaths (8.1%), frequent debridements (median, 11 cases), and amputation revisions (58%)., Conclusions: IFIs are an emerging trauma-related infection leading to significant morbidity. Early identification, using common characteristics of patient injury profile and tissue-based diagnosis, should be accompanied by aggressive surgical and antifungal therapy (liposomal amphotericin B and a broad-spectrum triazole pending mycology results) among patients with suspicious wounds.

Background: Timely and limited antibiotic prophylaxis (postinjury antimicrobial therapy) targeting specific traumatic injuries is a well-recognized measure to lessen posttraumatic infection. Modern military combat injuries raise significant challenges because of complex multiple injuries and limited data derived directly from well-controlled trials to base recommendations. Expert consensus review of available evidence led to published guidance for selection and duration of antimicrobial therapy for combat-related trauma infection prevention. This analysis evaluates antibiotic-prescribing practices by military physicians in the operational theater relative to the published guidance., Methods: Trauma history and infectious disease-specific inpatient care information is captured through the Joint Theater Trauma Registry along with a supplemental infectious disease module. Injury patterns are classified based on documented International Classification of Diseases-9th Revision codes with a composite assessment of each patient's injury pattern. Antimicrobial use categorized as prophylaxis is prescribed within the first 48 hours postinjury. Adherence to published guidance is reported along with patient characteristics and injury severity to assess for potential explanations of nonadherence., Results: During June to November 2009, 75% of the 610 eligible trauma patients received antimicrobial prophylaxis. Adherence to the recommended antibiotic agent on the day of injury was in the range of 46% to 50% for the most common extremity injury patterns and <10% in penetrating abdominal injuries. Antibiotics were given in 39% of patients sustaining injuries that are recommendations to not receive antimicrobial prophylaxis., Conclusions: This first evaluation of combat trauma-related antibiotic prophylaxis shows adherence levels comparable or superior to reported rates in civilian settings despite the austere, frequently mass casualty environment. Areas for interval surveillance and education-based strategies for improved adherence to practice guidance are identified.

Despite advances in resuscitation and surgical management of combat wounds, infection remains a concerning and potentially preventable complication of combat-related injuries. Interventions currently used to prevent these infections have not been either clearly defined or subjected to rigorous clinical trials. Current infection prevention measures and wound management practices are derived from retrospective review of wartime experiences, from civilian trauma data, and from in vitro and animal data. This update to the guidelines published in 2008 incorporates evidence that has become available since 2007. These guidelines focus on care provided within hours to days of injury, chiefly within the combat zone, to those combat-injured patients with open wounds or burns. New in this update are a consolidation of antimicrobial agent recommendations to a backbone of high-dose cefazolin with or without metronidazole for most postinjury indications, and recommendations for redosing of antimicrobial agents, for use of negative pressure wound therapy, and for oxygen supplementation in flight.

Despite advances in resuscitation and surgical management of combat wounds, infection remains a concerning and potentially preventable complication of combat-related injuries. Interventions currently used to prevent these infections have not been either clearly defined or subjected to rigorous clinical trials. Current infection prevention measures and wound management practices are derived from retrospective review of wartime experiences, from civilian trauma data, and from in vitro and animal data. This update to the guidelines published in 2008 incorporates evidence that has become available since 2007. These guidelines focus on care provided within hours to days of injury, chiefly within the combat zone, to those combat-injured patients with open wounds or burns. New in this update are a consolidation of antimicrobial agent recommendations to a backbone of high-dose cefazolin with or without metronidazole for most postinjury indications and recommendations for redosing of antimicrobial agents, for use of negative pressure wound therapy, and for oxygen supplementation in flight.