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.

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.

INTRODUCTION:Multidrug-resistant (MDR) Gram-negative infections complicate care of combat casualties. We describe the clinical characteristics, resistance patterns, and outcomes of Pseudomonas aeruginosa infections in combat casualties. METHODS:Combat casualties included in the Trauma Infectious Disease Outcomes Study with infections with and without P. aeruginosa isolation during initial hospitalization were compared. Pseudomonas aeruginosa from initial wound, blood, and serial isolates (≥7 days from previous isolate) collected from June 2009 through February 2014 was subjected to antimicrobial susceptibility testing, pulsed-field gel electrophoresis, and whole genome sequencing for assessing clonality. Multidrug resistance was determined using the CDC National Healthcare Safety Network definition. RESULTS:Of 829 combat casualties with infections diagnosed during initial hospitalization, 143 (17%) had P. aeruginosa isolated. Those with P. aeruginosa were more severely injured (median Injury Severity Score 33 [interquartile range (IQR) 27-45] vs 30 [IQR 18.5-42]; P < .001), had longer hospitalizations (median 58.5 [IQR 43-95] vs 38 [IQR 26-56] days; P < .001), and higher mortality (6.9% vs 1.5%; P < .001) than those with other organisms. Thirty-nine patients had serial P. aeruginosa isolation (median 2 subsequent isolates; IQR: 1-5), with decreasing antimicrobial susceptibility. Ten percent of P. aeruginosa isolates were MDR, associated with prior exposure to antipseudomonal antibiotics (P = .002), with amikacin and colistin remaining the most effective antimicrobials. Novel antimicrobials targeting MDR Gram-negative organisms were also examined, and 100% of the MDR P. aeruginosa isolates were resistant to imipenem/relabactam, while ceftazidime/avibactam and ceftolozane/tazobactam were active against 35% and 56% of the isolates, respectively. We identified two previously unrecognized P. aeruginosa outbreaks involving 13 patients. CONCLUSIONS:Pseudomonas aeruginosa continues to be a major cause of morbidity, affecting severely injured combat casualties, with emergent antimicrobial resistance upon serial isolation. Among MDR P. aeruginosa, active antimicrobials remain the oldest and most toxic. Despite ongoing efforts, outbreaks are still noted, reinforcing the crucial role of antimicrobial stewardship and infection control.

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Stenotrophomonas maltophilia is a pathogen with unique resistance patterns.We assessed 70 combat casualties with S. maltophilia clinical isolates to examineits role as a nosocomial pathogen incritically-ill trauma patients. Incidence density was 0.36 S. maltophilia infections per 100 patient-days (95% CI: 0.29-0.44). Patients predominantly had blast trauma (97%) and were critically injured (injury severity score [ISS] >25; 80%). Restricting to patients with ISS>15,50 patients with S. maltophilia infections were compared to 441 patients with infections attributed to othergram-negative bacilli. Patients with S. maltophilia infections had significantly more operating room visits prior to isolation, traumatic or early surgical amputations, longer hospitalization (median 71 vs 47 days), and higher overall mortality (10% vs 2%; P= 0.01). Initial and serial (>= 7 days between initial and subsequent isolation) S. maltophilia isolates had high susceptibility to trimethoprim-sulfamethoxazole and minocycline. Evaluation of newer agents awaiting CLSI breakpoints, including moxifloxacin, showed promising results. Published by Elsevier Inc.

ABSTRACT 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.

Abstract Background Deep soft-tissue infections (DSTIs) are a common complication of combat-related extremity trauma. We present an epidemiologic assessment of combat-related DSTIs among wounded military personnel. Methods Wounded personnel were included in the analysis if they sustained an open combat-related extremity wound (2009–2014), were admitted to a participating US military hospital, had a DSTI as the first confirmed extremity wound infection (within 30 days post-injury), started antibiotics ±3 days of DSTI diagnosis, and received ≥5 days of directed antibiotic treatment. Results Among 1961 combat casualties with open extremity wounds, 259 had a DSTI diagnosis with 173 (67%) having only 1 index DSTI and 86 (33%) having >1 index DSTI diagnosed on the same day. Nearly all patients (95%) were injured via a blast mechanism. Patients with >1 index DSTI were more severely injured (median injury severity score: 35 vs. 33; P = 0.009) and required large volume blood transfusions within 24 hours of injury (median units: 23 vs. 17; P < 0.001). Initial empiric antibiotic treatment largely involved carbapenem and vancomycin (77% and 72% of patients, respectively). For diagnosis timing, 130 (50%) patients had an early DSTI diagnosis (≤7 days post-injury), while the remaining 129 (50%) patients had a delayed diagnosis (>7 days post-injury). Patients with early DSTI diagnoses more often had >1 index DSTI (47% vs. 19% with delayed DSTI; P < 0.001). Polymicrobial DSTIs were common (73% of early DSTIs; 58% of delayed DSTIs) with Enterococcus spp. most frequently identified (56% of early DSTIs; 31% of delayed DSTIs) as well as Enterobacter spp., Escherichia coli, Pseudomonas aeruginosa, and Acinetobacter spp. Moreover, 26% and 39% of early and delayed DSTIs had multidrug-resistant Gram-negative bacteria. Receipt of >20 units of blood within 24 hours of injury and having >1 index DSTI were independently associated with an early DSTI diagnosis (odds ratio [OR]: 3.21; 95% CI: 1.47–7.02 and OR: 2.98; 95% CI: 1.63–5.42, respectively). Conclusion Multiple index DSTIs and massive blood transfusion requirement are associated with early infection onset post-injury. Awareness of wound microbiology findings relative to DSTI onset provides guidance on empiric antimicrobial therapy. Disclosures All authors: No reported disclosures.

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.

Clostridium difficile-associated diarrhea (CDAD) is an important cause of nosocomial diarrhea with increasing morbidity, mortality, and healthcare costs. There is growing recognition that critically ill trauma patients comprise a unique at risk population. This study describes the clinical epidemiology of CDAD in military trauma patients. Through the Trauma Infectious Disease Outcomes Study (TIDOS), patients with a diagnosis of confirmed (laboratory supported) or presumptive (diarrhea with treatment for CDAD in absence of lab confirmation) CDAD (September 2009–February 2014) were analyzed. Patient demographic, injury, and infection data were evaluated. CDAD severity was defined per 2017 IDSA guidelines. Of 2,660 patients, 19 and four patients with confirmed and presumptive CDAD, respectively, were identified with an incidence of 2.76/10,000 (95% CI: 1.75–4.15) occupied bed days. Sixteen (70%) had blast injuries, four had gunshot wounds, and threehad other injuries. Median age was 24 years (IQR 23, 31). Median injury severity score was 38 (IQR 26, 47). Severe and fulminant CDAD was diagnosed in 8 (35%) and six (26%), respectively. Patients had a median hospitalization of 12 days (IQR 9.5, 34) and threeOR visits (IQR 2, 6) prior to CDAD diagnosis. Nineteen (83%) patients were in the ICU and 17 (74%) were intubated prior to or upon diagnosis. Seventeen patients had ≥1 infection before CDAD diagnosis, largely pneumonia (47%) and skin and soft-tissue infections (47%). Most patients (96%) were on antibiotics pre-CDAD diagnosis: first generation cephalosporins (1GC; 96%), tetracyclines (87%), vancomycin (74%), carbapenems (70%), and fluoroquinolones (FQ; 57%). Five (22%) received clindamycin. Of the 2637 patients without CDAD, 91% received antimicrobials during hospitalization (86% a 1GC, 47% FQ, and 16% clindamycin). Median length of hospital stay after CDAD diagnosis was 34 days (IQR 16, 55). Treatment included only oral metronidazole in 15 patients, IV metronidazole in 2, and some combination of oral vancomycin, metronidazole, and IV metronidazole in 6. No patients died. Despite high rates of antimicrobial usage in this severely injured population, CDAD was uncommon. Though CDAD was severe or fulminant in >50%, no patients died. All authors: No reported disclosures.

BackgroundInfectious complications related to deployment trauma significantly contribute to the morbidity and mortality of wounded service members. The Trauma Infectious Disease Outcomes Study (TIDOS) collects data on US military personnel injured in Iraq and Afghanistan in an observational cohort study of infectious complications. Patients enrolled in TIDOS may also consent to follow-up through the Department of Veterans Affairs (VA). We present data from the first 337 TIDOS enrollees to receive VA healthcare.MethodsData were collected from the Department of Defense (DoD) Trauma Registry, TIDOS infectious disease module, DoD and VA electronic medical records, and telephone interview. Cox proportional hazard analysis was performed to identify predictors of post-discharge infections related to deployment trauma.ResultsAmong the first 337 TIDOS enrollees who entered VA healthcare, 111 (33%) had 244 trauma-related infections during their initial trauma hospitalization (2.1 infections per 100 person-days). Following initial discharge, 127 (38%) enrollees had 239 trauma-related infections (170 during DoD follow-up and 69 during VA time). Skin and soft-tissue infections and osteomyelitis were predominant during and after the initial trauma hospitalization. In a multivariate model, a shorter time to development of a new infection following discharge was independently associated with injury severity score ≥10 and occurrence of ≥1 inpatient infection during initial trauma hospitalization.ConclusionsIncident infections related to deployment trauma continue well after initial hospital discharge and into VA healthcare. Overall, 38% of enrolled patients developed a new trauma-related infection after their initial hospital discharge, with 29% occurring after the patient left military service.

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

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.

Prior studies have demonstrated high rates of colonization and infection with multidrug-resistant gram-negative bacilli (MDR-GNB) in injured military personnel. Our analysis shows that injuries inflicted during peak combat periods, massive blood transfusion requirement, and posttrauma cefazolin prophylaxis (additive effect with fluoroquinolones) were risk factors for MDR-GNB colonization.

There is concern that susceptibility of Staphylococcus aureus to tetracyclines may decrease due to use of antimalarial prophylaxis (doxycycline). We examined characteristics related to tetracycline resistance, including doxycycline exposure, in S. aureus isolates collected via admission surveillance swabs and inpatient clinical cultures from United States military personnel injured during deployment (June 2009-January 2012). Tetracycline class resistance was determined using antimicrobial susceptibility testing. The first S. aureus isolate from 168 patients were analyzed, of which 38 (23%) isolates were resistant to tetracyclines (class). Tetracycline-resistant isolates had a higher proportion of resistance to clindamycin (P=0.019) compared to susceptible isolates. There was no significant difference in tetracycline resistance between isolates collected from patients with and without antimalarial prophylaxis; however, significantly more isolates had tet(M) resistance genes in the doxycycline exposure group (P=0.031). Despite 55% of the patients receiving doxycycline as antimalarial prophylaxis, there was no association with resistance to tetracyclines.

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.

Multidrug-resistant Gram-negative bacilli infections (MDRGNI) in complex polytrauma patients is not well-described despite growing concern for antimicrobial resistance outpacing antimicrobial development. Characteristics and predictors for primary MDRGNI among wounded military personnel (2009-2014) are presented. Data on infectious outcomes and microbial recovery from US military personnel with deployment-related trauma medevac’d to Germany and transferred to a participating US hospital were collected through the Trauma Infectious Disease Outcomes Study. Multidrug resistance was defined as resistance to ≥3 of 4 antibiotic classes or production of extended spectrum β-lactamase or carbapenemases. Infections were restricted to first diagnosed infection. Logistic regression analysis assessed factors associated with MDRGNI. Among 2699 trauma admissions, 913 (34%) had an infection with 476 (18% of 2699) having a primary GN infection, of which 172 (36%) was MDR and 304 (64%) were susceptible. Among the MDRGNI patients, primary etiologic agents were Escherichia coli (56%), Acinetobacter spp. (47%), and Pseudomonas aeruginosa (16%). Median time to MDRGNI event was 7 days post-trauma with 75% of MDRGNIs diagnosed by 11 days post-trauma. MDRGNI patients had longer hospitalization (52 vs. 44 days for GN events; P < 0.001). Multivariate analysis identified prior MDRGN colonization (OR: 6.5, 95% CI: 3.8-11.1) as the strongest predictor for MDRGNI. Use of antibiotics ≥2 days identified increasing risk with combinations of First-generation cephalosporin and fluoroquinolone (FQ) (OR: 2.0, 95% CI: 1.2-3.3) and vancomycin and carbapenem (OR: 2.2, 95% CI: 1.2-4). With ≥5 days exposure, risk was significantly increased with Firstgeneration cephalosporin and FQ (OR: 4.9, 95% CI: 1.9-12.5), but not vancomycin and carbapenem. A high proportion of patients in our study had a MDRGNI as their first infection. Increased risk was associated with prior MDRGN colonization as well as escalating antibiotic class, expanded coverage combination regimens, and duration of exposure. As the largest cohort analysis of trauma patients, these findings inform antimicrobial stewardship and infection control practices. All authors: No reported disclosures.