INTRODUCTION:Combat casualty care is resource-intensive; however, the impact of battlefield-related infections on healthcare utilization is not fully understood. We assessed factors associated with hospitalization among wounded military personnel by infection outcome. MATERIALS AND METHODS:The study population for this cross-sectional retrospective analysis included military personnel wounded during deployment (June 1, 2009-December 31, 2014), admitted to Landstuhl Regional Medical Center (Germany), and transferred to participating military hospitals in the continental United States. Patients consented to the review of electronic medical records through the Military Health System (MHS) Data Repository. Patients were classified as having a trauma-related infection with a multidrug-resistant Gram-negative bacillus, infection attributed to other pathogens, or without infection during initial hospitalization. Hospital healthcare utilization within the first 2 weeks post-injury among patients with infections was assessed to identify factors associated with longer hospitalization. RESULTS:The study population consisted of 1,018 patients; 148 patients with a multidrug-resistant Gram-negative bacilli infection, 320 with an infection attributed to another pathogen, and 550 without infections. Hospital length of stay was a median of 59.5 days for patients with multidrug-resistant Gram-negative bacilli infections compared to 42 days for infections with other pathogens and 22 days for patients without infections (P < .001). Critical care (e.g., intensive care unit admission/duration, mechanical ventilation, and procedures), and collection of clinical cultures were more frequent among patients with multidrug-resistant Gram-negative bacilli infections compared with those with other pathogens and without infections (P < .05) and are plausible factors to potentially explain why their longer hospitalization. Patients with multidrug-resistant Gram-negative bacilli infections received more aminoglycosides, aminopenicillin, antipseudomonal penicillin, antiparasitics, antifungals, carbapenems, macrolides, polymyxins, trimethoprim-sulfamethoxazole, and vancomycin than patients with infections attributed to other pathogens (P < .05), with an overall greater duration of antimicrobial use (median: 51 vs. 38 days; P < .001). When adjusted for injury severity, clinical microbiology workups, surgeries, and other factors shown to be associated with hospitalization in the multivariate model, having an infection with a multidrug-resistant Gram--negative bacillus was associated with a stay of 5 extra days for every 30 days stayed by a patient with infections attributed to other pathogens. CONCLUSIONS:Combat casualty care is associated with high resource utilization and the occurrence of multidrug-resistant Gram-negative bacilli infections significantly adds to the healthcare burden on the MHS. Examination of incremental changes in healthcare costs associated with battlefield-related infections is warranted to inform the allocation of needed resources to treat these patients.

INTRODUCTION:Traumatic brain injuries (TBIs) are associated with substantial morbidity and mortality. We examined characteristics and outcomes among military personnel with battlefield-related penetrating TBI (pTBI) compared to closed TBI (cTBI) and non-head injuries (without cranial injuries). MATERIALS AND METHODS:Military personnel admitted to participating U.S. military hospitals (2009-2014) were classified based on injury patterns: pTBI, cTBI (head Abbreviated Injury Scale [AIS] ≥3), and non-head (≥1 non-head injury AIS ≥3). Propensity score and inverse probability of treatment weighting (IPTW) were used to assess associations with mortality, hospital stay, and infection burden. RESULTS:The study population included 106 pTBI patients, 259 cTBI patients, and 715 patients with non-head injuries. Patients with pTBIs were more severely injured with differing injury mechanisms compared to the other 2 groups. Patients with pTBIs had more critical care requirements versus both cTBI and non-head injury patients (P < .05) and longer hospitalization (median 27 days vs. 22; P = .041) compared to cTBI patients. More central nervous system (CNS) infections were diagnosed among patients with pTBIs (11.3%) versus cTBIs (1.2%) and non-head injuries (0.7%; P < .001). Although the overall proportion of patients who developed non-CNS infections was not significantly different between the TBI groups, there was a higher proportion among pTBI versus non-head injury patients (53.8% vs. 40.8%; P = .012). Patients with pTBIs also had less skin and soft-tissue infections and more pneumonia compared to non-head injury patients (P < .05). There was no significant difference in the proportion of mortality between the pTBI and cTBI patients (7.6% vs. 3.1%); however, it was higher compared to patients with non-head injuries (1.0%; P < .001). Sustaining any TBI (penetrating or closed) was associated with greater risk of mortality compared to non-head injuries (risk ratio: 3.71; 95% CI, 1.83-7.55). CONCLUSIONS:Patients with pTBIs are critically injured with substantial critical care requirements and morbidity. Between patients with pTBIs and cTBIs, there was not a significant difference in non-CNS infection burden or mortality, but pTBI patients did have longer hospitalization. When compared to severely injured military personnel with non-head injuries using propensity scores and IPTW analysis, sustaining a TBI (penetrating or closed) was not associated with having more non-CNS infections or a longer hospital stay. This may be a result of the high injury severity (median of 26) and relative occurrence of polytrauma in the total population. Patients with TBIs (penetrating or closed) did have a greater risk of mortality compared to patients with non-head injuries.

Lower respiratory infections are a major contributor to morbidity after battlefield trauma. Between 2009-10, 8.5% of 423 US military casualties developed pneumonia (PNA) with a higher proportion (18.5%) in patients admitted to ICUs. Using a larger population, we examined characteristics associated with PNA after battlefield trauma.Characteristics of Wounded Military Personnel Who Did and Did Not Develop PneumoniaICU – intensive care unit IED – improvised explosive device; IQR – interquartile range1 Patients frequently sustained polytrauma, so the numbers will sum to more than the total number of patientsCharacteristics of Patients with Pneumonia Stratified by Isolation of Multidrug-Resistant (MDR) BacteriaICU – intensive care unit IED – improvised explosive device; IQR – interquartile range1 Patients frequently sustained polytrauma, so the numbers will sum to more than the total number of patients Data were collected via the Trauma Infectious Disease Outcomes Study, an observational study of infections in wounded US military personnel (2009-2014). PNA was defined using standardized criteria. Chi-square (or Fisher exact) and Mann-Whitney U tests were used for categorical and continuous variables, respectively.Frequency of Isolates Recovered from First Respiratory Culture with Growth1 Other Gram-negative bacteria include Achromobacter spp., Acinetobacter spp. (non-baumannii), Burkholderia spp., Chryseobacterium spp., Elizabethkingia spp., Enterobacter non-cloacae spp., Haemophilus parainfluenzae, Haemophilus spp., Hafnia spp., Proteus spp. (non-mirabilis), Ochrobactrum spp., Ralstonia spp., Raoultella spp., Serratia spp. (non-marcescens), and unidentified Gram-negative bacteria2 Other Gram-positive bacteria include Corynebacterium spp. and Rothia dentocariosa3 Other fungal and yeast organisms include Hansenula anomala, Mycelia sterile, Penicillium spp., Trichosporon spp., and unidentified yeast A total of 2,687 wounded military personnel were assessed, with 324 (12%) patients developing PNA. The PNA patients had higher injury severity scores (ISS; median 38 vs 17; p< 0.001) with more injuries to the head/neck (66% vs 44%), thorax (55% vs 21%), abdomen (44% vs 16%), groin/perineum (23% vs 7%), spine (33% vs 19%), upper extremities (56% vs 36%), and lower extremities (69% vs 59%) than non-PNA patients (p≤0.001, Table 1). PNA patients also had more ICU admissions (98% vs 46%), greater mechanical ventilation requirements (91% vs 25%), longer hospitalizations (median 44 vs 19 days) and higher crude mortality 4% vs 0.7% (p< 0.001). Among PNA patients, 92 (28%) had multidrug-resistant (MDR) bacteria isolated and the MDR PNA group had greater median ISS (43 vs 32 p=0.003), blood units in 1st 24 hours of injury (median 22 vs 13 p=0.001), ICU admissions (100% vs 97% p=0.010), mechanical ventilation (99% vs 88% p=0.002), and hospital stays (median 54 vs 40 days p< 0.001) than PNA patients with non-MDR bacteria (Table 2). Most frequent bacteria were Pseudomonas aeruginosa (N = 269, 11% MDR) and Acinetobacter baumannii (N = 158, 82% MDR, Table 3). Battlefield-injured patients who developed PNA had greater injury severity along with more frequent injuries to the torso than non-PNA patients. PNA patients with MDR isolates were more severely injured with higher crude mortality than those with susceptible pathogens. These data support developing interventions to prevent PNA in these patients. Further analysis of clinical factors to include imaging and symptom reporting is planned. All Authors: No reported disclosures

Thermal injuries disrupt both the innate and adaptive immune systems, resulting in an immunocompromised state that makes infection a frequent complication. Examination of military personnel with battlefield-related burns revealed that 18% developed ≥ 1 infection and those with greater total body surface area burned (TBSA) had more infections. Here, we examine infections with regard to burn injury pattern and severity. Data were collected through the Trauma Infectious Disease Outcomes Study (TIDOS), an observational study of infections in U.S. military personnel who sustained deployment-related injuries (2009–2014). Patients who sustained burn injuries and were admitted to the U.S. Army Institute of Surgical Research Burn Center at Brooke Army Medical Center were included. Patients with incomplete injury pattern data were excluded. Burn injury patterns were grouped and evaluated by infection syndromes. Among 144 burn patients, 136 (94%) were included in the analysis. The patients were primarily male (N=135, 99%) with combat injuries (N=83, 61%) sustained via a blast (N=76, 56%), resulting in critical injury severity (median injury severity score: 30; interquartile range: 27-41.5). There was a total of 317 burn injuries with upper extremity burns being most frequent (30%), followed by head (26%) and lower extremity burns (23%; Table 1). Lower extremity and torso burns had the greatest TBSA (% median 4.6 and 3.5, respectively). For each burn injury, pneumonia accounted for the highest proportion of infections (occurrence ranged 18.5%-45.4% per injury), followed by bloodstream infections (BSI, 9.8%-36.3%). Four patients had severe burn injury patterns (TBSA of the affected area ≥ 20%), with three having torso burns and one having lower extremities burns. All four patients with severe burns developed pneumonia. While the majority of burns in this study were not severe by TBSA, those that were went on to develop ≥ 1 infection, and patients with torso and genitalia burns had more pneumonia, skin and soft-tissue infections, and BSI. Understanding burn injury patterns and risk for infectious complications is critical for burn injury management and developing potential strategies for preventing infections. All Authors: No reported disclosures

Background:The Military Health System offers geographically distributed SARS-CoV-2 incidence estimates to support critical national pandemic surveillance, but this has not been previously assessed. The objective was to identify confirmed, probable, and possible SARS-CoV-2 infections with laboratory and clinical evidence and compare cumulative incidence to the general United States population. Methods:An observational, retrospective epidemiologic study using medical records from the United States Military Health System (inclusive of active duty) collected from outpatient and inpatient facilities worldwide, both United States Military and non-military treatment facilities. Direct standardization to the general US population was used to calculate sex-adjusted cumulative incidence, stratified by age, for 10 Health and Human Services regions for active duty and non-active duty beneficiary populations, with Spearman's rho correlations for age and region strata. Results:Among Military Health System beneficiaries, 2,219,987 cases were identified, with 27.4% laboratory-confirmed cases alongside 35.0% probable and 37.6% possible cases identified using clinical ICD-10-CM evidence. Peaks in cases occurred November 2020-January 2021, August 2021-September 2021, and January 2022. Age-stratified and sex-adjusted cumulative incidence across 10 geographical regions reflected these temporal patterns among both active duty (90% of age and region-specific correlation coefficients >0.7) and non-active duty beneficiaries (80% of age and region-specific correlation coefficients >0.7). Cumulative incidence was higher among active duty beneficiaries compared to the United States general population, particularly those ages 18-49 years, with adjusted cumulative incidence ratios consistently greater than 1. The cumulative incidence ratios for non-active duty beneficiaries were more consistent and closer to 1. The sensitivity analysis of laboratory-confirmed cases among active duty personnel demonstrated consistently lower adjusted cumulative incidence than United States general population. Conclusion:Temporal patterns in cases among Military Health System beneficiaries reflect cases measured nationally by the Centers for Disease Control and Prevention. Applying a comprehensive algorithm of clinical and laboratory data from a large electronic health system, such as the Military Health System, may improve case capture during an emergent epidemic providing incidence estimates and regional impact in support of U. S. national surveillance.

BackgroundA significant proportion of patients presenting with post-acute sequelae of COVID-19 (PASC) have been found to meet diagnostic criteria for certain disorders of the autonomic nervous system. Substantial gaps remain in our understanding of these conditions. Our objective is to evaluate demographic and medical factors associated with PASC dysautonomia in active duty US Service members (ADSM). Additionally we assessed for risk factors in those diagnosed with COVID-19 for PASC dysautonomia, and differences in those with PASC dysautonomia and non-PASC dysautonomia.MethodsA matched case control dataset (n = 1,367,961) of ADSM diagnosed with COVID-19 matched with ADSM with no evidence of COVID-19 was utilized to assess associations of demographic and clinical factors with PASC dysautonomia. Logistic regression modeling was used to assess differences among those diagnosed with COVID-19. Conditional logistic regression modeling using propensity score weighting was used for comparisons between those with PASC dysautonomia and non-PASC dysautonomia.ResultsWe identified 619,983 COVID-19 cases (158 PASC dysautonomia) and 747,978 controls (219 non-PASC dysautonomia). Among COVID-19 cases, factors positively associated with PASC dysautonomia were white, non-Hispanic race/ethnicity, female sex, younger age, northeast region, more severe COVID-19 infection, and comorbid depression or anxiety. Among those with dysautonomia, those with PASC dysautonomia were more likely to be of female sex, younger, in the northeast region, and less likely to have comorbid anxiety.ConclusionPASC dysautonomia is rare in ADSM but associated with increased care utility and often prolonged diagnostic pathways. Important demographic and COVID-19 specific risk factors are associated with the development of PASC dysautonomia. PASC dysautonomia has significant differences in risk factors as compared to non-PASC dysautonomia, warranting further examination. These findings may support clinician awareness and prognostication and prompt further research on the pathophysiology and management of these conditions.

Abstract Background Skin and soft-tissue infections (SSTIs), commonly Staphylococcus aureus, are an important cause of morbidity in congregate military populations with high rates among military recruits. We characterized SSTI epidemiology over an ∼10-year period at a military training facility in GA (largest U.S. training facility; ∼30,000 recruits per year). Methods SSTI data were collected from US Army Infantry recruits during basic training, through four studies (2 observational and 2 interventional studies spanning 2010-2019) and pooled into a single resource for retrospective research. SSTI characteristics (syndromes and diagnosis timing) and microbiology are described. Results The study population includes 3288 recruits who developed SSTIs during the training period for a total of 3690 SSTIs. Median age was 19 years and median time for initial SSTI development was 7 (IQR 4 -11) weeks of training. Cellulitis (N=1600, 43%) and abscesses (N=1098, 30%) were most common and median time to diagnosis was 7 (IQR 4-11) and 8 (IQR 4-11) weeks of training, respectively. Cultures were collected from 1620 (44%) SSTIs, including 77% of abscesses. Methicillin-resistant and methicillin-susceptible S. aureus (MRSA and MSSA) were identified in 784 (48%) and 610 (38%) cultures, respectively (Table). Other findings include coagulase-negative staphylococci (4%), group A streptococci (0.2%), and group B streptococci (0.4%). A total of 373 recruits had ≥ 2 SSTIs and 55% of the subsequent 402 SSTIs were abscesses. Median time to 2nd and 3rd SSTIs was 10 (IQR 7.5-12) and 12 (IQR 10-13) weeks of training, respectively. There was a significant difference among the bacterial distribution for abscesses (p< 0.001) with MRSA contributing the highest proportion (62%), followed by MSSA (28%). MRSA was also identified with 64% of the 166 subsequent SSTIs with cultures. Conclusion Cellulitis and abscesses are frequent infections affecting military recruits during high-intensity congregate training. The most common bacteria with purulent infections (i.e., abscesses), as well as subsequent infections, was MRSA. Pooling data from multiple studies allows for examination of syndromes and etiology to inform targeted interventions. Disclosures David Tribble, MD, DrPH, AstraZeneca: The IDCRP and HJF were funded to conduct an unrelated phase III COVID-19 monoclonal antibody immunoprophylaxis trial as part of US Govt COVID Response

Abstract Background The clinical relevance of the cefazolin inoculum effect (CIE) in methicillin-susceptible Staphylococcus aureus (MSSA) isolates has been debated, with some studies showing poor outcomes in CIE(+) MSSA patients treated with β-lactams and others finding no effect. As less is known about CIE in trauma patients, we examined characteristics of US wounded military personnel with MSSA infections with and without CIE. Methods Data and initial / serial (defined as isolation ≥ 7 days from prior isolate) MSSA isolates were collected from the Trauma Infectious Disease Outcomes Study (6/09-12/14). Isolates collected for surveillance were excluded. Antimicrobial susceptibility testing was performed via BD Phoenix Automated Microbiology System using CLSI criteria. Isolates were tested for CIE by broth microdilution utilizing standard (∼5x105 cfu/mL) and high (HI) inocula (∼5x107 cfu/mL). CIE(+) was defined as a MIC increase to ≥ 16 μg/mL with HI. Results Among 112 MSSA patients, 6 had CEI(+) and 106 CIE(-) isolates. The patients were primarily males (99%) who sustained critical injuries (mean injury severity score 36) via blasts (65%), requiring critical care (80%) and prolonged hospitalization (mean 45 days, Table 1). All patients received 1st generation cephalosporin or β-lactam with Staphylococcus coverage. There were no significant differences between the CIE(+) and CIE(-) patients. No CIE(+) patients had serial isolates, and no patients in either group died. A total of 179 MSSA isolates were assessed: 9 (5%) CIE(+) and 170 (95%) CIE(-). The majority of MSSA isolates were from respiratory (N=87, 49%), wound (N=72, 40%), and blood cultures (N=12, 7%). All isolates were uniformly susceptible to cefazolin, ampicillin-sulbactam, and ceftaroline, and had reduced susceptibility to doxycycline and tetracycline (Table 2). When compared to CIE(-) isolates, CIE(+) isolates had decreased susceptibility to clindamycin and erythromycin. Conclusion CIE was uncommon with battlefield MSSA infections. Evaluation of clinical outcomes was limited (i.e., small numbers), but serial CIE(+) isolation was not observed. Although CIE(+) isolates were more resistant to clindamycin and erythromycin, isolates remained susceptible to other first-line antimicrobials. Disclosures All Authors: No reported disclosures

Advancements in combat casualty care and personnel protective equipment led to increased survivability of grievous battlefield injuries during U.S. Operations Iraqi Freedom and Enduring Freedom (OIF/OEF). Accompanying these important advances were high rates of post-trauma infections (25–30%), including high-consequence infections, such as invasive fungal wound infections (IFIs), sepsis, and infections attributed to multidrug-resistant Gram-negative bacilli (MDRGN), which are associated with long-term morbidity (e.g., limb loss) and mortality. 1–3 The Trauma Infectious Disease Outcomes Study (TIDOS) collected data from wounded warriors from 2009–2014 and findings have been utilized to further the understanding of combat trauma-related infections, as well as identifying infection risk factors and examining clinical outcomes. 3 While TIDOS has focused on infections following trauma sustained during OIF/OEF, there is a high likelihood that similar high-consequence infections will occur in future conflicts. A further concern is that near-peer scenarios in future conflicts would result in a lack of air superiority for medical evacuation, resulting in prolonged field care. Between 2001 and 2010, combat casualties injured in Iraq or Afghanistan arrived at Landstuhl Regional Medical Center (LRMC; Germany) a median of 38 hours (~1.5 days) following injury. As sepsis and IFIs typically develop a median of 3 days post-injury (median of 7 days post-injury for MDRGN infections), 1 3 4 any delays in casualty evacuation from the operational theater to higher role facilities will result in prolonged field care and presumably greater morbidity from these high-consequence infections. Thus, healthcare providers across a range of expertise along the evacuation chain of care, coupled with limited forward diagnostic and therapeutic capabilities need maximal decision support tailored to the specific patient and injury setting to mitigate these infections. As information collected from combat casualties on injury characteristics, clinical signs, symptoms, and laboratory findings have the potential to support both risk stratification and clinical decision-making along the pathway of care from the prehospital setting through medical evacuation to more advanced capabilities, 5 we are utilizing TIDOS data to develop a machine learning-based clinical decision support tool (CDST) for longitudinal use from the prehospital setting through hospital admission. Design: Retrospective cohort study utilizing machine learning. Setting: Injury characteristics, clinical signs, symptoms and laboratory findings collected in the austere (prehospital) setting and following admission to a higher role of care military hospital. Participants: U.S. active-duty military personnel wounded during deployment. Main Outcome(s) and Measure(s): In the prehospital setting, particularly with prolonged field care, use of the CDST will improve triage and early decision support through use of immediately available data related to injury characteristics (severity, wounding pattern, mechanism, and environmental setting) and vital signs (within 1st 72 hours), identifying those at highest risk for developing high-consequence infections (figure 1). The tool may also be used on a longitudinal basis as the patient transitions through the echelons of care, acquiring greater accuracy for risk prediction as clinical and laboratory data become available in the hospital setting. Machine learning and deep learning will provide novel insights into how combinations of independent risk factors influence infection aetiology and clinical outcome coupled with information on pretest probability (prevalence) of high-priority microbial threats. The use of a functional tool that meets the needs of front-line care givers and focuses on early indicators available in the prehospital setting will directly support frontline casualty care, as well as prolonged and en-route care. Abstract A22 Figure 1 Predictive modelling workflow and application. The initial risk stratification model will be created using the earliest data obtained before admission to hospitals, while longitudinal support model will be generated using data obtained after admission to hospitals. The lower arrows of left and right columns indicate the future use of the models The view(s) expressed herein are those of the author(s) and do not reflect the official policy or position of Uniformed Services University of the Health Sciences, Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., National Institutes of Health or the Department of Health and Human Services, the Defense Health Agency, the Departments of the Air Force, Navy, Army, or the Department of Defense, or the U.S. Government. Support for this work was provided by the Infectious Disease Clinical Research Program (IDCRP), a Department of Defense program executed through the Uniformed Services University of the Health Sciences, Department of Preventive Medicine and Biostatistics through a cooperative agreement with The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc. (HJF). This project has been funded by the National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), under Inter-Agency Agreement Y1-AI-5072, the Defense Health Program, U.S. DoD, under award HU0001190002, and through Defense Health Program award HU00012320031. The funders had no role in study design, data collection, data analysis, data interpretation, or writing the manuscript. Tribble DR, Murray CK, Lloyd BA, et al . After the battlefield: infectious complications among wounded warriors in the trauma infectious disease outcomes study. Mil Med. 2019; 184 (Suppl 2):18–25. Campbell WR, Li P, Whitman TJ, et al . Multi-drug-resistant gram-negative infections in deployment-related trauma patients. Surg Infect. 2017; 18 :357–67. Lewandowski LR, Weintrob AC, Tribble DR, et al . Early complications and outcomes in combat injury related invasive fungal wound infections: a case-control analysis. J Orthop Trauma. 2016; 30 :e93–9. Lloyd B, Weintrob A, Rodriguez C, et al . Effect of early screening for invasive fungal infections in U.S. service members with explosive blast injuries. Surg Infect . 2014; 15 :619–26. Potter BK, Forsberg JA, Silvius E, et al . Combat-related invasive fungal infections: development of a clinically applicable clinical decision support system for early risk stratification. Mil Med. 2019; 184 :e235–42. All authors have completed the ICMJE uniform disclosure form at http://www.icmje.org/disclosure-of-interest/ and declare: DT, NE, ISP, LS, DC, and KM received funding through their institution for this study as reported in the funding statement. DT, NE, ISP, and LS also received funding from the Defense Health Program and USU through their institution for other research protocols during the past 36 months. DT, NE, and LS received support from grants paid to their institutions for travel to meetings/conferences. DT serves on Data Safety Monitoring Boards (DSMB) for the National Institute of Allergy and Infectious Diseases Division of Microbiology and Infectious Diseases and Department of Defense, and serves on the University of Vermont COBRE Advisory Board. DC serves on a DSMB for a clinical trial being run by IDCRP hosted at the Uniformed Services University of the Health Sciences. DC is also an editor of the journal, Machine Learning and Artificial Intelligence in Diagnostics . NE received payment from the George Washington University Milken Institute School of Public Health for lectures per being part-time faculty.

ABSTRACT Introduction Vaccine mandates have been used to minimize the duty days lost and deaths attributable to infectious disease among active duty Service members (ADSMs). In response to the global COVID-19 pandemic, in August 2021, the U.S. DoD issued a COVID-19 vaccine mandate for all ADSMs. This study aimed to investigate COVID-19 vaccine uptake among the ADSM population, as well as factors associated with timing of COVID-19 vaccine receipt. Materials and Methods This study included ADSMs on active duty between January 1, 2020, and June 30, 2022. Univariate analyses investigated associations between demographic factors (age, sex, race, ethnicity, branch of service, rank, and state of residence) and COVID-19 diagnosis with the following outcomes: (1) time to primary series initiation in relation to the DoD vaccine mandate, (2) time between doses of the 2-dose primary series, and (3) time between booster eligibility and receipt. This research received an exempt determination by the USU Human Research Protection Program. Results In total, 1,799,466 ADSMs were included, with 90% receiving ≥1 COVID-19 vaccine dose during the study period and 77% initiating the primary series prior to the mandate. Over 80% of ADSMs received a complete primary series, with 96% of those adhering to the recommended regimen. The history of COVID-19 diagnosis was associated with the later receipt of all doses. Conclusions COVID-19 vaccine uptake was high among all ADSMs, with the majority initiating the primary series before the mandate. The high vaccine uptake among ADSMs shown here may be used as a guide to both military and civilian pandemic policy and outreach efforts related to enhanced vaccine uptake.

Abstract Background Acinetobacter baumannii (ACB) emerged as a key pathogen during the war in Iraq and was designated as a serious threat in the 2013 Centers for Disease Control’s antimicrobial resistance report. We describe the characteristics of wounded military personnel with ACB infections. Methods Data were obtained from the Trauma Infectious Disease Outcomes Study, an observational study of US service members injured in Iraq and Afghanistan (6/09-12/14). Patients who had ≥ 1 positive infecting ACB isolate were assessed. Multidrug resistance (MDR) was defined as resistance to ≥ 3 classes of antimicrobials or production of extended-spectrum β-lactamase or carbapenemase. Categorical variables were compared by Chi-square or Fisher’s Exact and continuous variables by Mann-Whitney U. Results Among 160 patients with ACB infections, 116 (73%) and 43 (27%) had MDR and non-MDR ACB, respectively. All were male with a median age of 23.5 years and the majority sustained injuries in combat (96%) in Afghanistan (93%) (Table 1). Blast was the primary injury mechanism (86%), resulting in high injury severity. There was a total of 283 ACB infections with 222 (78%) MDR and 61 (22%) non-MDR; 59 patients had ≥ 1 ACB infection (median of 2 [IQR 2-4] infections). Skin and soft-tissue infections (48%) were most common, followed by pneumonia (23%), bloodstream infections (15%), and osteomyelitis (11%) (Table 2). Compared to non-MDR ACB patients, patients with MDR ACB had greater transfusions requirements within 1st 24 hours post-injury (median 25 vs 15 units p=0.01, Table 1). There was a non-significant trend toward more abdominal/pelvic/groin injuries among MDR ACB patients (60% vs 42% with non-MDR p=0.051). Hospital duration was a median 52.5 days and crude mortality was 3% with no significant difference between the groups. Conclusion Battlefield casualties with ACB infections were characterized by high injury severity, frequently caused by blast trauma with MDR ACB more often in those with larger volume blood transfusions. Wound infections and pneumonia were most common. Overall, ACB infection patients were critically ill with large resource utilization regardless of MDR status. Further analysis to compare outcomes with non-ACB infection outcomes is warranted. Disclosures David Tribble, MD, DrPH, AstraZeneca: The IDCRP and HJF were funded to conduct an unrelated phase III COVID-19 monoclonal antibody immunoprophylaxis trial as part of US Govt COVID Response

ABSTRACT Introduction The long-term impact of deployment-related trauma on mental and physical health-related quality of life (HRQoL) among military personnel is not well understood. We describe the mental and physical HRQoL among military personnel following deployment-related polytrauma after their discharge from the hospital and examine factors associated with HRQoL and longitudinal trends. Materials and Methods The U.S. military personnel with battlefield-related trauma enrolled in the Trauma Infectious Diseases Outcomes Study were surveyed using SF-8 Health Surveys at 1 month post-discharge (baseline) and at follow-up intervals over 2 years. Inclusion in the longitudinal analysis required baseline SF-8 plus responses during early (3 and/or 6 months) and later follow-up periods (12, 18, and/or 24 months). Associations of demographics, injury characteristics, and hospitalization with baseline SF-8 scores and longitudinal changes in SF-8 scores during follow-up were examined. Survey responses were used to calculate the Mental Component Summary score (MCS) and the Physical Component Summary score (PCS). The MCS focuses on vitality, mental health, social functioning, and daily activity limitations, whereas PCS is related to general health, bodily pain, physical functioning, and physical activity limitations. Longitudinal trends in SF-8 scores were assessed using chi-square tests by comparing the median score at each timepoint to the median 1-month (baseline) score, as well as comparing follow-up scores to the immediately prior timepoint (e.g., 6 months vs. 3 months). Associations with the 1-month baseline SF-8 scores were assessed using generalized linear regression modeling and associations with longitudinal changes in SF-8 were examined using generalized linear regression modeling with repeated measures. Results Among 781 enrollees, lower baseline SF-8 total scores and PCS were associated with spinal and lower extremity injuries (P < .001) in the multivariate analyses, whereas lower baseline MCS was associated with head/face/neck injuries (P < .001). Higher baseline SF-8 total was associated with having an amputation (P = .009), and lower baseline SF-8 total was also associated with sustaining a traumatic brain injury (TBI; P = .042). Among 524 enrollees with longitudinal follow-up, SF-8 scores increased, driven by increased PCS and offset by small MCS decreases. Upward SF-8 total score and PCS trends were associated with time post-hospital discharge and limb amputation (any) in the multivariate analyses (P < .05), whereas downward trends were independently associated with spinal injury and developing any post-discharge infection (P ≤ .001). Patients with lower extremity injuries had lower-magnitude improvements in PCS over time compared to those without lower extremity injuries (P < .001). Upward MCS trend was associated with higher injury severity (P = .003) in the multivariate analyses, whereas downward trends were independently associated with having a TBI (P < .001), time post-hospital discharge (P < .001), and occurrence of post-discharge infections (P = .002). Conclusions Overall, HRQoL increased during the 2-year follow-up period, driven by PCS improvement. Increasing HRQoL was associated with time since hospital discharge and limb amputation, whereas a downward trend in HRQoL was associated with spinal injury and post-discharge infection. The longitudinal decline in MCS, driven by TBI occurrence, time since hospital discharge, and developing post-discharge infections, emphasizes the importance of longitudinal mental health care in this population.

Combat casualties are frequently injured in austere settings where modern imaging modalities are unavailable. Exploratory laparotomies are often performed in these settings when there is suspicion for intra-abdominal injury. Prior studies of combat casualties reported non-therapeutic laparotomy (NTL) rates as high as 32

Abstract Background Thermal injury alters the host response, making burn patients more susceptible to infections. In fact, infections represent the most frequent complication and cause of mortality in burn patients. We describe the epidemiology, clinical characteristics, timing, and outcomes of infections among wounded military personnel with burns. Methods Data were collected through the Trauma Infectious Disease Outcomes Study, an observational study of US service members injured in Iraq and Afghanistan (6/09-12/14). Patients who sustained ≥1 burn injury and were admitted to the Burn Center at Brooke Army Medical Center were included in the analysis. Infections were defined using standardized criteria. For patients with multiple infections, only the initial infection was assessed. Results Among 144 burn patients, 99% were males and 62% had combat-related burns with a median total body surface area (TBSA) of 6% (IQR 3-14%) thermally injured. Infections were diagnosed in 26 (18%) patients with pneumonia being the predominant initial syndrome (N=16, 62%), followed by skin and soft-tissue infections (N=6, 23%), bloodstream infections (N=3, 12%), and intra-abdominal infections (N=1, 4%). Median number of days to each of these initial infecting syndromes were 4 (IQR 3-5), 7 (IQR 4-12), 7 (IQR 6-7), and 17 (IQR 17-17) days, respectively. Patients with infections were more severely injured with greater TBSA (median 31 vs 5) and Baux scores (median 59 vs 29), and were more likely to have combat trauma, inhalation injury, require mechanical ventilation, and have longer time to definitive grafting (Table 1). Microbiology of initial infections varied with 35% of patients having polymicrobial infections (Table 2). Gram-negative organisms were recovered from 20 (77%) patients, of whom 20% had a multidrug-resistant Gram-negative. Gram-positive organisms and fungi were identified in 42% and 8% of patients, respectively. Conclusion Improved understanding of risk factors and the timing of infections in this unique population is critical for effective management. Patients with infections were more severely injured, had higher rates of inhalational injury, and longer days to definitive grafting. Initial infections were more commonly pneumonia. Disclosures David R. Tribble, DrPH, AstraZeneca: The HJF, in support of the USU IDCRP, was funded to conduct or augment unrelated Phase III Mab and vaccine trials as part of US Govt. COVID19 response.

Background Among combat injured, invasive fungal infections (IFIs) result in significant morbidity. Cultures and histopathology are the primary diagnostic methods for IFIs, but they have limitations. We previously evaluated a panfungal polymerase chain reaction assay, which was 83% sensitive and 99% specific for angioinvasive IFIs. Here, we evaluated 3 less resource-intensive seminested assays targeting clinically relevant fungi in the order Mucorales and genera Aspergillus and Fusarium.Methods Formalin-fixed paraffin-embedded tissue specimens from a multicenter trauma IFI cohort (2009-2014) were used. Cases were US military personnel injured in Afghanistan with histopathologic IFI evidence. Controls were patients with similar injury patterns and no laboratory IFI evidence (negative culture and histopathology). Seminested assays specific to Mucorales (V4/V5 regions of 18S rDNA), Aspergillus (mitochondrial tRNA), and Fusarium (internal transcribed spacer [ITS]/28A regions of DNA) were compared with a panfungal assay amplifying the internal transcribed spacer 2 region of rDNA and to histopathology.Results Specimens from 92 injury sites (62 subjects) were compared with control specimens from 117 injuries (101 subjects). We observed substantial agreement between the seminested and panfungal assays overall, especially for the order Mucorales. Moderate agreement was observed at the genus level for Aspergillus and Fusarium. When compared with histopathology, sensitivity and specificity of seminested assays were 67.4% and 96.6%, respectively (sensitivity increased to 91.7% when restricted to sites with angioinvasion).Conclusions Prior studies of seminested molecular diagnostics have focused on culture-negative samples from immunocompromised patients. Our findings underscore the utility of the seminested approach in diagnosing soft-tissue IFIs using formalin-fixed paraffin-embedded tissue samples, especially with angioinvasion. We tested seminested polymerase chain reaction assays for identifying clinically relevant fungi in formalin-fixed tissue specimens obtained from those injured in combat. Although the overall sensitivity was modest at 67.4%, it performed well in specimens with documented angioinvasion, with a sensitivity of 91.7%.

Abstract Background Efficacy of a two-dose COVID-19 vaccine series at preventing infection is ∼50-80% after the first dose and ∼95% following the second, if completed on the recommended schedule. Although >90% of active-duty servicemembers (SM) completed a primary series, understanding timing of doses as recommended among Military Health System (MHS) beneficiaries is vital to prevent COVID-19 outbreaks. Methods Active-duty and National Guard/Reserve on active-duty SM aged ≥17 years who were beneficiaries of the MHS during 1/1/2020-6/30/2022 and completed a two-dose primary series were assessed for timing of the vaccines (stratified as early, grace period, recommended, and late) and associated demographic factors. SARS-CoV-2 infection (laboratory confirmed or ICD-10 diagnosis) prior to initiating the primary series, between the two doses, or after completion of the primary series was also assessed. Descriptive statistics (chi-square) were used to identify associations with timing of the second primary dose. Results Among 1,426,436 SM, 97.9% were aged 17-49, 81.4% were male, 69.8% were white, and 35.6% served in the Army (Table 1). Overall, 92.7% received their second primary dose in the recommended or grace periods, and 7.3% were late. Timing of the first and second vaccine doses showed peaks in the months following the vaccine EUA, as well as after the DoD vaccine mandate. SM who had a COVID diagnosis between their two primary doses were more likely to receive a late second dose, although the diagnosis was likely not the cause for the late second dose, as were those who received their first dose during the pre-mandate period. SM receiving a late second dose were more likely to be younger, in the Air Force or Army, and reside in HHS regions 4, 5, 6, 7, and 8.Table 1.Demographics and COVID-19 status by timing of the second dose in a two-dose COVID-19 vaccine series. Conclusion Most of the population received their second primary dose on the recommended schedule or earlier. However, SM in the Air Force and Army were more likely to receive their second dose later than recommended, as were those who lived in the South, West, and Midwest and those who had COVID-19 infection between their primary doses. Future research will investigate adverse disease outcomes associated with a delayed second dose in the primary series, as well as potential interactions between factors predicting delayed second dose uptake. Disclosures Simon Pollett, MBBS, AstraZeneca: The IDCRP and the Henry M. Jackson Foundation (HJF) were funded to conduct an unrelated phase III COVID-19 monoclonal antibody immunoprophylaxis trial Timothy Burgess, MD, MPH, AstraZeneca: The IDCRP and the Henry M. Jackson Foundation (HJF) were funded to conduct an unrelated phase III COVID-19 monoclonal antibody immunoprophylaxis trial

Abstract Background Identifying predictors of COVID-19 vaccination receipt in servicemembers (SM) is critical for protecting US military health. We report active-duty (AD) SM vaccination across 20 months of eligibility and assess factors associated with adoption of the primary series vaccine pre/post the Department of Defense (DoD) mandate, 8/24/21. Methods Data on AD, National Guard/Reserve on AD, ages >17, Military Health System (MHS) beneficiaries (1/1/20 - 6/30/22) were extracted from the MHS Data Repository. Descriptive statistics were assessed using Chi-square. Univariate and multivariate modeling was conducted to examine the relationship of demographics and COVID-19 diagnosis with initiation of the COVID-19 primary series vaccine pre mandate. Statistical significance was defined as p< 0.05. Results Of 1,889,750 SMs, most were ages 17-49, male, lived in the US, white, not Hispanic, and served in the Army. Overall, 90% received >1 primary series dose; with 85% completing the primary series, 5% had partial primary series, and 10% had no record of vaccination at the end of observed time. Of SMs with >1 primary series dose, 78% received the 1st dose pre mandate (11% had COVID-19 prior to 1st dose) and 22% post mandate (19% had COVID-19 prior to 1st dose; p< 0.001) (Table 1 and Fig. 1). SM ages >50 had higher odds of vaccine initiation pre mandate (P< 0.001), compared to ages 17-49 (Table 2). States in the Midwest and North central US had lower odds of pre mandate initiation compared to states in the southeast, aOR=0.85 and 0.87 respectively. Black/African American SM had lower odds (aOR=0.71) of pre mandate initiation, and Asians or Pacific Islanders had higher odds (aOR=1.78) (P< 0.001) compared to white SM (Table 2). Coast Guard and Navy had higher odds of pre mandate initiation; Air Force and Marine Corps had lower odds (P< 0.001) compared to Army. SM who had COVID infection prior to 1st primary dose had lower odds (P< 0.001) of initiating pre mandate.Table 1:Demographic factors of the active-duty and Guard/Reserve on active-duty population who received ≥1 primary series vaccine dose according to primary series initiation timing (pre-mandate versus post-mandate) 1 Domestic regions of residence are defined by Health and Human Services (HHS) regions and all others are considered outside the US. Figure 1: COVID-19 vaccine primary series initiation pre/post DoD mandate, by month among Servicemembers in the Military Health System Table 2. Univariate and adjusted associations with receiving a first primary dose prior to the COVID-19 vaccine military mandate (odds ratios>1 indicate higher odds of receiving the vaccine before the mandate) 1 The model was adjusted for all factors shown in the table: age, gender, region of residence, race, Hispanic ethnicity, branch of service, COVID-19 infection prior to initiation primary series, and active-duty status. 2 Domestic regions of residence are defined by Health and Human Services (HHS) regions and all others are considered outside the US. Conclusion Although the majority of SM initiated the COVID-19 primary series prior to the DoD mandate, age, race, history of COVID-19 diagnosis, and region were associated with uptake post-mandate. Understanding the factors that affect vaccine uptake among SM is important to guide vaccine policy to enhance medical readiness and optimal vaccine effectiveness. Disclosures Simon Pollett, MBBS, AstraZeneca: The IDCRP and the Henry M. Jackson Foundation (HJF) were funded to conduct an unrelated phase III COVID-19 monoclonal antibody immunoprophylaxis trial Timothy Burgess, MD, MPH, AstraZeneca: The IDCRP and the Henry M. Jackson Foundation (HJF) were funded to conduct an unrelated phase III COVID-19 monoclonal antibody immunoprophylaxis trial

BACKGROUND: Penetrating brain injuries are a potentially lethal injury associated with substantial morbidity and mortality. We examined characteristics and outcomes among military personnel who sustained battlefield-related open and penetrating cranial injuries during military conflicts in Iraq and Afghanistan.METHODS: Military personnel wounded during deployment (2009-2014) were included if they sustained an open or penetrating cranial injury and were admitted to participating hospitals in the United States. Injury characteristics, treatment course, neurosurgical interventions, antibiotic use, and infection profiles were examined.RESULTS: The study population included 106 wounded personnel, of whom 12 (11.3%) had an intracranial infection. Posttrauma prophylactic antibiotics were prescribed in more than 98% of patients. Patients who developed central nervous system (CNS) infections were more likely to have undergone a ventriculostomy ( p = 0.003), had a ventriculostomy in place for a longer period (17 vs. 11 days; p = 0.007), had more neurosurgical procedures ( p < 0.001), and have lower presenting Glasgow Coma Scale ( p = 0.01) and higher Sequential Organ Failure Assessment scores ( p = 0.018). Time to diagnosis of CNS infection was a median of 12 days postinjury (interquartile range, 7-22 days) with differences in timing by injury severity (critical head injury had median of 6 days, while maximal [currently untreatable] head injury had a median of 13.5 days), presence of other injury profiles in addition to head/face/neck (median, 22 days), and the presence of other infections in addition to CNS infections (median, 13.5 days). The overall length of hospitalization was a median of 50 days, and two patients died.CONCLUSION: Approximately 11% of wounded military personnel with open and penetrating cranial injuries developed CNS infections. These patients were more critically injured (e.g., lower Glasgow Coma Scale and higher Sequential Organ Failure Assessment scores) and required more invasive neurosurgical procedures. (J Trauma Acute Care Surg. 2023;95: S72-S78.)

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.