Showing papers by "Clinton K. Murray published in 2022"

IDCRP Combat-Related Extremity Wound Infection Research.

Abstract: 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.

Prognostic Value of Sequential Organ Failure Assessment (SOFA) Score in Critically-Ill Combat-Injured Patients

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

Virological and Serological Assessment of US Army Trainees Isolated for Coronavirus Disease 2019

Abstract: Abstract Background Laboratory screening for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a key mitigation measure to avoid the spread of infection among recruits starting basic combat training in a congregate setting. Because viral nucleic acid can be detected persistently after recovery, we evaluated other laboratory markers to distinguish recruits who could proceed with training from those who were infected. Methods Recruits isolated for coronavirus disease 2019 (COVID-19) were serially tested for SARS-CoV-2 subgenomic ribonucleic acid (sgRNA), and viral load (VL) by reverse-transcriptase polymerase chain reaction (RT-PCR), and for anti- SARS-CoV-2. Cluster and quadratic discriminant analyses of results were performed. Results Among 229 recruits isolated for COVID-19, those with a RT-PCR cycle threshold >30.49 (sensitivity 95%, specificity 96%) or having sgRNA log10 RNA copies/mL <3.09 (sensitivity and specificity 96%) at entry into isolation were likely SARS-CoV-2 uninfected. Viral load >4.58 log10 RNA copies/mL or anti-SARS-CoV-2 signal-to-cutoff ratio <1.38 (VL: sensitivity and specificity 93%; anti-SARS-CoV-2: sensitivity 83%, specificity 79%) had comparatively lower sensitivity and specificity when used alone for discrimination of infected from uninfected. Conclusions Orthogonal laboratory assays used in combination with RT-PCR may have utility in determining SARS-CoV-2 infection status for decisions regarding isolation.

Application of Bayesian Methods to Help Interpret the VANCO Trial Results

Abstract: Objective: To determine whether a Bayesian analysis changes the results of the VANCO trial. Design: A secondary analysis of a randomized clinical trial using Bayesian methods. Setting: Thirty-six US trauma centers. Patients: Patients ages 18–80 years with a tibial plateau or pilon fracture deemed high risk of infection and definitively treated with plate and screw fixation. Intervention: Patients were randomly allocated to receive 1000 mg of intrawound vancomycin powder at their definitive fixation or to a control group that received no topical antibiotics. Main Outcome Measurements: A deep surgical site infection requiring operative treatment within 6 months of definitive fixation. Secondary outcomes included gram-positive and gram-negative–only deep surgical site infections. Results: Of the 980 patients randomized, 874 (89%) had at least 140 days of follow-up and were included in this Bayesian analysis. The estimated probability that intrawound vancomycin powder reduces the risk of a deep surgical site infection is >98% [relative risk (RR), 0.66; 95% credible interval (CrI), 0.46–0.98]. There is a >99% chance intrawound vancomycin powder reduces gram-positive infections and an 80% chance the magnitude of this risk reduction exceeds 35% (RR, 0.52; 95% CrI, 0.33–0.84) exists. It is unlikely (44%) that intrawound vancomycin powder prevents gram-negative surgical site infections (RR, 1.06; 95% CrI, 0.48–2.45). Conclusions: There is a high probability (>98%) that intrawound vancomycin powder reduces deep surgical site infections in patients with tibial plateau or pilon fractures at high risk of infection and even more likely it reduces deep infections with gram-positive pathogens (>99%). Level of Evidence: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.

1388. Seasonality of Microbiology of Combat-related Wound Infections in Afghanistan

Abstract: Abstract Background We examined the seasonality of wounds and wound infections, including occurrence of multidrug resistance, among combat casualties injured in Afghanistan. Methods The Trauma Infectious Disease Outcomes Study is a retrospective observational study of infectious complications among military personnel wounded during deployment (06/09-12/14). Wound cultures obtained ≤7 days following injury in Afghanistan were assessed. Epidemiologic, clinical, and microbiologic data were analyzed by injury season [winter (1 Dec-28/29 Feb), spring (1 Mar-31 May), summer (1 Jun-31 Aug), and fall (1 Sep-30 Nov)]. Multidrug-resistant (MDR) determinations for Gram-negative and Gram-positive organisms were per standardized definitions. Results The study population included 316 patients with a median of 3.5 (IQR 3-5) days from injury to initial culture. Gram-negatives (N=188, 59.5%) were more commonly isolated from wound cultures in summer (N=81, 43.1%) and fall (N=57, 30.3%) versus winter (N=18, 9.6%) and spring (N=32, 17%) (p< 0.001). The MDR Gram-negatives (N=69, 21.8%) were more common in summer (N=26, 37.7%), and fall (N=26, 37.7%) versus winter (N=3, 4.3%) and spring (N=14, 20.3%) (p=0.028). Wound infections were diagnosed in 198 (63%) patients. The pattern for infecting Gram-negative isolates (N=143, 72.2%, Table 1) was similar to that of overall Gram-negative isolates: summer (79.5%) and fall (83.6%; p< 0.001); MDR Gram-negatives (summer, 25.6%) and (fall, 41.8%; p=0.015). Escherichia coli and Enterobacter spp. were the most common infecting Gram-negative bacilli with no significant difference across the seasons. There was a higher proportion of infecting Acinetobacter baumannii isolates in the summer and fall compared to winter and spring. Infecting Gram-positive isolates (N=128, 65%) were not significantly different by season. Anaerobes associated with infections were also identified (N=30, 15%) with a higher proportion in the winter compared to summer, fall, and spring (p=0.036). Conclusion Gram-negatives, including MDR Gram-negative infecting organisms, were more common in summer/fall months in service members injured in Afghanistan. This may have implications for empiric antibiotic coverage during these months. 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.