Septic Trauma Research Articles

The Risk Factors for Mortality among Septic Trauma Patients: A Retrospective Cohort Study Using the National Trauma Data Bank.

In trauma patients, the development of sepsis as a hospital complication is significantly associated with morbidity and mortality. We aimed to assess the risk factors associated with in-hospital mortality among trauma patients who developed sepsis during their hospital stay. Material and methods. Using the 2017 National Trauma Data Bank, a retrospective cohort study was conducted to identify adult trauma patients who developed sepsis during their hospital stay. The primary outcome of interest was in-hospital mortality. Multivariate analysis was used to determine the risk factors associated with in-hospital mortality. 1782 trauma patients developed sepsis. 567 patients (31.8%) died during their hospital stay. The following patient factors were associated with higher odds of in-hospital mortality: age (OR = 1.045 95% CI = 1.036-1.054), chronic renal failure (OR = 2.564 95% CI = 1.528-4.301), and liver cirrhosis (OR = 3.699 95% CI = 2.267-6.033). Patients who developed cardiac arrest (OR = 4.994 95% CI = 3.381-7.378), acute kidney injury (OR = 3.808 95% CI = 2.837-5.110), acute respiratory distress syndrome (OR = 1.688 95% CI = 1.197-2.379), and stroke (OR = 1.998 95% CI = 1.075-3.714) during their hospital stay had higher odds of mortality. Higher Glasgow Coma Scale (13-15) at presentation was associated with lower odds of mortality (OR = 0.467 95% CI = 0.328-0.667). Among trauma patients who developed sepsis, age, chronic renal failure, cirrhosis, the development of cardiac arrest, acute kidney injury, acute respiratory distress syndrome, and stroke in the hospital were associated with in-hospital mortality. These factors can be used to identify patients who are at higher risk of adverse outcomes and implement standardized or protocol-driven methods to improve patient care.

Assessment of serum interleukin-28 as a biomarker to predict mortality in traumatic patients with sepsis

BackgroundSerious trauma due to various factors is a major global public issue, and sepsis is a major cause of trauma-associated mortality. Timely diagnosis and suitable treatment of post-traumatic sepsis are crucial to improve the hospital outcome of traumatic patients. IL-28 is a newly discovered member of IFN-λ family with multiple functions in inflammatory response. To date, its role in the pathogenic mechanisms of post-traumatic sepsis still remains unknown. MethodsIn total, 20 healthy controls, 55 traumatic patients without sepsis and 54 traumatic patients with sepsis were enrolled in this study. Serum IL-28A/B levels were investigated by ELISA. ResultsIL-28A/B levels were significantly increased in traumatic patients compared to healthy volunteers. Moreover, septic trauma patients displayed a significant increase in IL-28A/B levels compared with non-septic patients. In septic patients, IL-28A/B were negatively correlated with IFN-γ, IL-5, IL-13 and IL-17, and positively associated with IL-10. Moreover, IL-28A (AUC: 0.821, 95 %CI: 0.693–0.949) and IL-28B (AUC: 0.811, 95 %CI: 0.691–0.931) were both beneficial to predict increased mortality risk in septic trauma patients, though there was no statistical difference in the predictive value between them. ConclusionsEarly serum levels of IL-28A/B were associated with the development of post-trauma sepsis and could be applied to assess the outcome of traumatic patients with sepsis. Thus, IL-28 may be a potential indicator for post-traumatic sepsis.

Select topics in the management of critically ill children.

The purpose of this review article is to discuss considerations for the critically ill child presenting to an emergency department (ED) with pharmacists who have minimal to no pediatric training. In 2015, 17% of all children visited an ED, constituting 30 million visits. The majority of these children were treated at community hospitals where pediatric care resources, including a pediatric-trained pharmacist, may be limited. Because of the complex array of ages and disease states, the care of critically ill children in the ED creates many concerns for adult and community hospitals. This article will focus on several common disease states seen in the pediatric ED, including septic shock, trauma, status epilepticus, and diabetic ketoacidosis. Critically ill children admitted to a community or adult ED provide therapeutic dilemmas and medication safety concerns. A pharmacist with training or experience in pediatrics can have a major impact in patient outcomes in many of the disease states seen in these pediatric patients. This article highlights several key differences between critically ill pediatric and adult patients to better prepare all pharmacists to care for these vulnerable patients.

T-helper-17, Regulatory T-helper Cells Related Serum Markers and IL-13 in the Outcome of Polytraumatic Patients with Bacteremia.

Bacteremia and sepsis are associated with high mortality, increased hospital stays, and associated costs, especially in trauma patients. Sepsis is a fatal immunological disorder and its pathophysiology is still poorly understood. To ascertain the role of T-helper lymphocyte-related inflammatory serum cytokines in trauma patients with blood culture positive with Gram-negative bacteria. Peripheral blood samples (5 ml) were collected from 40 trauma patients on the day of obtaining positive blood culture (i.e., day 0), followed by an appropriate antimicrobial treatment and sample acquisition on day 4 and only once from 40 age-matched healthy controls. Bead-based cytometric analysis was used to quantify extracellular levels of 16 serum cytokines. The cytokine profiles were compared with those in healthy controls and then correlated to clinical outcomes. A total of 40 patients were enrolled during the study period. Of these, 24 patients (60%) were discharged while 16 (40%) had a fatal outcome. Statistically significant elevated levels of serum IL-6, IFN-γ, TNF-α, IL-17A, IL-17F, and IL-4 were observed in septic patients, while lowered IL-13 levels correlated significantly with a favorable outcome. Sepsis following trauma elicits a heightened immune response in the body and provokes the production of a diverse array of cytokines that is both pro-inflammatory and anti-inflammatory. However, the unique cytokine profile of septic trauma patients is still not well understood.

Malnutrition – An underestimated factor in the inpatient treatment of traumatology and orthopedic patients: A prospective evaluation of 1055 patients

IntroductionSuboptimal nutritional status is often observed among hospitalized patients across all medical specialties. The objective of the present study was to (1) analyze the prevalence of malnutrition in hospitalized orthopedic and trauma patients and (2) to evaluate the relationship between malnutrition and selected clinical outcomes. Materials and methodsThe prospective field study was conducted between 06/2014 and 06/2015 in a German level I trauma center (Department of Traumatology, Septic Trauma Surgery and Arthroplasty) with a total number of 1055 patients. At hospital admission, patients were checked for malnutrition using the validated Nutritional Risk Screening (NRS). Patients at risk for malnutrition were defined as NRS≥3. Quality of life (SF-36) was assessed to evaluate the physical and mental health status prior to hospitalization. Clinical outcomes under consideration included 1) rate of adverse events, 2) length of hospitalization, and 3) mobilization after operative and conservative treatment. Patients were included independently of surgical intervention or age. Results22.3% (235) of our patients were at risk for malnutrition (NRS≥3) while a regular nutritional status (NRS<3) was diagnosed in 77.7% (819). The highest prevalence of malnutrition was found in Septic Surgery with 31.0% (106), followed by Traumatology with 19.2% (100) and Arthroplasty with 15.1% (29). Higher prevalence of malnutrition was observed among patients with typical fractures of the elderly, such as lumbar spine and pelvis (47.4%), proximal femur (36.4%) and proximal humeral (26.7%) fractures. Furthermore, patients at risk for malnutrition showed prolonged hospitalization (13.7±11.1 vs. 18.2±11.7days), delayed postoperative mobilization (2.2±2.9 vs. 4.0±4.9days) and delayed mobilization after conservative treatment (1.1±2.7 vs. 1.8±1.9days). A statistically significant correlation of NRS with each parameter (Spearman's rank correlation, p<0.05) was observed. The incidence of adverse events in patients at risk for malnutrition was statistically significantly higher compared to that of patients with a regular nutritional status (37.2% vs. 21.1%, p<0.001). ConclusionsMalnutrition is widespread regarding hospitalized patients in the field of orthopedic and trauma surgery and results in suboptimal clinical outcome. It should be considered as an important factor that significantly contributes to delayed recovery. Especially elderly trauma patients and patients suffering from postoperative infections should be monitored carefully during hospitalization.

Early prevention of trauma-related infection/sepsis.

Trauma still represents one of the major causes of death worldwide. Despite the reduction of post-traumatic sepsis over the past two decades, the mortality of septic trauma inpatients is still high (19.5–23 %). Early prevention of sepsis development can aid in the subsequent treatment of patients and help improve their outcomes. To date, the prevention of trauma-related infection/sepsis has mainly included infection prevention (e.g., surgical management, prophylactic antibiotics, tetanus vaccination, immunomodulatory interventions) and organ dysfunction prevention (e.g., pharmaceuticals, temporary intravascular shunts, lung-protective strategies, enteral immunonutrition, acupuncture). Overall, more efficient ways should be developed to prevent trauma-related infection/sepsis.

Assessment of early lymphopenia after cardiac arrest

A significant decrease in circulating lymphocytes can occur after septic shock and severe trauma and is associated with a poor outcome. After cardiac arrest (CA), the return of spontaneous circulation is associated with a significant inflammatory response that can also mimic the same alterations, but lymphocyte count has not been studied in this setting.

Secondary lumbar spondylosis in University of Uyo Teaching Hospital, Uyo, Nigeria: Radiographic correlation with incidence and concomitant discovertebral pathologies

Introduction: Lumbar spondylosis is an age-related degenerative disk disease of the lumbar spine. It could be preceded by known discovertebral lesions resulting in secondary lumbar spondylosis. Objectives: To determine the incidence of secondary lumbar spondylosis using lumbosacral radiographic evaluations. Study Designs/Settings: A cross-sectional prospective study. Radiology Department, University of Uyo teaching hospital, Uyo, Nigeria. Patient Sample: Two hundred and sixty-two patients. Outcome Measured: Pathologies are evaluated based on features seen on twin lumbosacral radiographs that demonstrate secondary spondylosis. Materials and Methods: Anterior-posterior and lateral plain radiographs of patients were done under standardized conditions. Studied period was 1 st May, 2011 to 12 th July, 2012. Results were analyzed using SSPS 13. computer package. Results: A total of 262 patients aged 10-89 years with mean age of 48.9 and standard deviation of 25.4 were studied. Males were 138 and females were 124. 173 patients constituting 66.03% of the studied population had lumbar spondylosis. A total of 57 patients (female to male ratio − 1.36:1) had secondary lumbar spondylosis. This constituites 32.95% of population with spondylosis. Secondary lumbar spondylosis was commonest in the 4 th to 6 th decade. A total of 17.54% of patients with secondary spondylosis were younger than 40 years. The commonest associated pathology was spondylolisthesis, n=25 cases (43.86%) with female predominance. The least were septic spondylitis and trauma (1.75% each). Other conditions were osteoporosis, metastasis, lumbarization, spina bifida, and Pott's disease. Conclusions: The commonest coexistence with lumbar spondylosis in Uyo, Nigeria is lumbar spondylolisthesis.

Innate Immune Dysfunction in Trauma Patients

Innate Immune Dysfunction in Trauma Patients

Clostridium-difficile-assoziierte Infektionen in der septischen Unfallchirurgie: Eine Analyse von 159 Patienten

Clostridium difficile-associated infections are severe nosocomial infections. In recent studies, dramatic increases of CD-associated infections for the U.S.A. and Germany have been described, which leads to additional risk for patients and higher costs. Despite several studies, there is no study available which analyses the incidence of CD-associated infections on a septic ward at a level 1 trauma centre. Therefore, this study was performed to analyse the incidence and risk factors of developing a CD-associated infection in septic trauma patients. All patients treated between January 2002 and December 2009 at the septic ward of a level 1 trauma centre, who developed a CD-associated diarrhoea or pseudomembranous colitis, were included in this retrospective study. Information about age, sex, admission diagnosis, indication for antibiotic therapy, length of antibiotic therapy, number of administered antibiotics, length of hospital stay, type of treatment of the CD-associated infection as well as the mortality rate was gleaned from the patients' medical records. Furthermore, the relation of developing a CD-associated infection was determined for the following factors: (i) age > 65 years versus < 65 years; (ii) male versus female; (iii) single versus multiple antibiotic therapy; (iv) cephalosporins versus remaining antibiotic groups. Between January 2002 and December 2009 6378 patients with surgical infection were treated at our level 1 trauma centre, whereas a total of 159 patients (2.5%) developed during the hospital stay a Clostridium difficile-associated diarrhoea. The incidence of CD-associated infection increased dramatically in 2009 and was more than quadrupled compared with 2002 or 2003. Patients over 65 years of age developed more frequently a CD-associated infection compared to patients less than 65 years of age (OR 1.96, 95% CI 1.4 to 2.7). There was no difference between males and females as well as between multiple antibiotic therapy and single antibiotic therapy (OR 0.96, 95% CI 0.7 to 1.3). Cephalosporins were the most often administered antibiotics with a median value of 45.9% followed by gyrase inhibitors with a median value of 17.2%. However, there were no differences between antibiotic groups (OR 1.11; 95% CI 0,87-1,5). In conclusion, CD-associated infections are frequent nascent infections on a septic ward at a level 1 trauma centre. This could result in a therapeutic dilemma in the future, especially in septic surgery, where antibiotic therapy is an essential component of the therapy. Thus, further prospective clinical and experimental studies are essential.

P-16 Assessment of muscle oxygen saturation in the early phase of extracorporeal life support

Introduction. Patients with extracorporeal life support (ECLS) may be at risk of inadequate tissue perfusion and oxygenation that leads to multiple-organ dysfunction. Near-infrared spectroscopy has emerged in recent years as a non-invasive tool for monitoring peripheral oxygenation (StO2) in various tissues, including muscle. Using a dynamic vascular occlusive test (VOT), StO2 abnormalities were identified during septic shock and severe trauma, suggesting microvascular dysfunction [1-3]. We wondered whether StO2 abnormalities could exist during the early phase of ECLS.

Epidemiology and risk factors of sepsis after multiple trauma: An analysis of 29,829 patients from the Trauma Registry of the German Society for Trauma Surgery*

The objectives of this study were 1) to assess potential changes in the incidence and outcome of sepsis after multiple trauma in Germany between 1993 and 2008 and 2) to evaluate independent risk factors for posttraumatic sepsis. Retrospective analysis of a nationwide, population-based prospective database, the Trauma Registry of the German Society for Trauma Surgery. A total of 166 voluntarily participating trauma centers (levels I-III). Patients registered in the Trauma Registry of the German Society for Trauma Surgery between 1993 and 2008 with complete data sets who presented with a relevant trauma load (Injury Severity Score of ≥ 9) and were admitted to an intensive care unit (n = 29,829). None. Over the 16-yr study period, 10.2% (3,042 of 29,829) of multiply injured patients developed sepsis during their hospital course. Annual data were summarized into four subperiods: 1993-1996, 1997-2000, 2001-2004, and 2005-2008. The incidences of sepsis for the four subperiods were 14.8%, 12.5%, 9.4%, and 9.7% (p < .0001), respectively. In-hospital mortality for all trauma patients decreased for the respective subperiods (16.9%, 16.0%, 13.7%, and 11.9%; p < .0001). For the subgroup of patients with sepsis, the mortality rates were 16.2%, 21.5%, 22.0%, and 18.2% (p = .054), respectively. The following independent risk factors for posttraumatic sepsis were calculated from a multivariate logistic regression analysis: male gender, age, preexisting medical condition, Glasgow Coma Scale score of ≤ 8 at scene, Injury Severity Score, Abbreviated Injury ScaleTHORAX score of ≥ 3, number of injuries, number of red blood cell units transfused, number of operative procedures, and laparotomy. The incidence of sepsis decreased significantly over the study period; however, in this decade the incidence remained unchanged. Although overall mortality from multiple trauma has declined significantly since 1993, there has been no significant decrease of mortality in the subgroup of septic trauma patients. Thus, sepsis has remained a challenging complication after trauma during the past 2 decades. Recognition of the identified risk factors may guide early diagnostic workup and help to reduce septic complications after multiple trauma.

Modern management of the septic trauma patient

The principles of management of the septic trauma patient are similar, though in some ways more challenging, than the septic patient without trauma. These principles include confirmation that new or progressive organ failure is secondary to infection, identification of the site of infection, the administration of appropriate antibiotics, and surgical management of infection, if required.

Intracapsular pressure and interleukin-1β cytokine in hips with acetabular dysplasia

Background and purpose Several studies have demonstrated an increased intracapsular pressure in several hip disorders such as septic arthritis, synovitis, and trauma. We therefore measured the intracapsular pressure in different positions in early dysplasic hips and its relation to the concentration of interleukin-1β (IL-1β), the volume of joint fluid, and the clinical and radiographic findings before a periacetabular osteotomy.Methods 12 female patients (12 hips, mean age 35 (18–52)) with hip dysplasia were investigated. The intracapsular pressure was recorded and we investigated possible correlations with the Harris hip score, the Tönnis scale, radiographic findings, the volume of joint fluid, and the concentration of IL-1β.Results An increased intracapsular pressure was noted, especially in flexion or extension with internal rotation. We found positive correlations between the intracapsular pressure and both the volume of joint fluid and the concentration of IL-1β.Interpretation Increased intracapsular pressure varied with different positions, indicating the presence of synovitis resulting from early osteoarthritis in dysplastic hips. Positive correlations between the pressure and both the concentration of IL-1β and the volume of joint fluid suggest that the inflammatory cytokines produced by the synovial membrane as a consequence of mechanical instability of the hip joint may be of importance for the initiation and/or development of osteoarthritis in dysplastic hips.

Resuscitation volume and multiple organ dysfunction syndrome

Patients with severe infections and major trauma often develop multiple organ dysfunction syndrome (MODS). Aggressive fluid resuscitation can be involved in such a process and several lines of evidence have demonstrated the detrimental effects of large crystalloid-based resuscitation strategies on MODS. Additionally, fluid-restrictive strategies have been associated with a decreased frequency of acute respiratory distress syndrome (and a shorter time to recover from it) and with trends toward a shorter length of hospital stay and lower mortality. Recent knowledge of the pathophysiology of septic shock and severe trauma indicates that a release of inflammatory mediators occurs early in the course of the disease. These mediators, especially pro-inflammatory cytokines as well as hypopituitary adrenal axis dysfunction, are involved in cardiac dysfunction and vasodilatation-induced hypotension. Taking into account this combination of severe inflammation and secondary changes in endocrine profile through an ear...

Relationship of taurine and other amino acids in plasma and in neutrophils of septic trauma patients

Recently, an interdependency of plasma taurine and other amino acids as well as metabolic and clinical variables implicating therapeutic options was reported. This result may be an indication that plasma taurine levels are directly related to intracellular levels. Therefore, the aim of this study was to analyse the possible relationship between taurine levels in plasma and in neutrophils, the relationship to other amino acids, and variables quantifying metabolic impairment and severity of sepsis in multiple trauma patients developing sepsis. After multiple trauma taurine decreased significantly in plasma in thirty-two patients as well as within the neutrophil and does not recover in sepsis. Lower individual levels in the neutrophil did not follow lower individual levels in plasma and no correlation of taurine in plasma and in the neutrophils could be observed. In sepsis, only plasma showed an interdependency of taurine, aspartate, and glutamate. No association between taurine plasma or intracellular levels and SOFA score as indicator for severity of sepsis or metabolic variables was observed. After multiple trauma and in sepsis, taurine uptake in cells (which is regulated in different ways), and intracellular taurine (which serves e.g. as an osmolyte) can be influenced. Therefore a prediction of the neutrophil taurine pool seems not fully possible from taurine plasma levels. Intracellular taurine has some unique properties explaining the missing interdependency despite some similarities in osmoregulation and metabolic interactions to other amino acids. The association of taurine, aspartate, and glutamate in plasma cannot be simply transferred to the neutrophils intracellular level. The clinical meaning of the plasma correlation remains unclear. A dependency of plasma and neutrophil taurine to severity of sepsis and to metabolic variables seems not possible because of the multifactorial pathophysiology of sepsis.

Epidemiology of sepsis in patients with traumatic injury

To characterize the epidemiology of sepsis in trauma. Analysis of a prospectively collected administrative database (Pennsylvania trauma registry). All trauma centers in the state of Pennsylvania (n = 28) All patients (n = 30,303) with blunt or penetrating injury admitted to Pennsylvania trauma centers over a 2-yr period (January 1996-December 1997). None. Incidence of sepsis in trauma, independent predictors of sepsis, and associated mortality were evaluated. Analyses controlled for age, gender, preexisting disease, injury type, Revised Trauma Score, Injury Severity Score, and admission vital signs. Sepsis occurred in 2% of all patients and was associated with a significant increase in mortality (23.1% vs. 7.6%, p < .001) compared with nonseptic patients. Respiratory tract infections were the most common cause of sepsis. Septic trauma patients had increased ICU length of stay (21.8 vs. 4.7 days, p < .001) and hospital length of stay (34.1 vs. 7.0 days, p < .001). Logistic regression identified Injury Severity Score, Revised Trauma Score, lower admission Glasgow Coma Scale score, and preexisting diseases as significant independent predictors of sepsis, whereas female gender was associated with a decreased risk of sepsis. Increasing injury severity measured by Injury Severity Score was associated with increased incidence of sepsis. Moderate (Injury Severity Score 15-29) and severe injury (Injury Severity Score >/=30) had a six-fold and 16-fold, respectively, increased incidence of sepsis compared with mild injury. Multivariate analysis confirmed that the effect of sepsis on mortality was greater in trauma patients with mild injury than those with moderate or severe injury. This study reports the incidence of sepsis and its associated mortality and critical care resource utilization in a large, state-wide population-based trauma registry. Increasing injury severity, measured by Injury Severity Score, was a significant independent predictor of sepsis in trauma and was associated with increased intensive care unit resource utilization and mortality. These results suggest that future studies should attempt to delineate interventional strategies to prevent sepsis in trauma patients with moderate and severe injury, given their significantly increased risk.

Early elevation of soluble CD14 may help identify trauma patients at high risk for infection.

Elevated levels of soluble CD14 (sCD14) have been implicated in both gram-positive and gram-negative sepsis, and it has been associated with high mortality in trauma patients who become infected. Eleven healthy volunteers and 25 adult trauma patients with multiple injuries and a mean Injury Severity Score of 32 participated. Whole blood was obtained at intervals. Immunohistochemistry was used to quantify membrane CD14 (mCD14), by flow cytometry and plasma levels of sCD14 by enzyme-linked immunosorbent assay. Analysis of variance and Student's T test with Mann-Whitney posttest were used to determine significance at p < 0.05. On posttrauma day 1, sCD14 was significantly different in the plasma of infected patients compared with normal controls (7.16 +/- 1.87 microg/mL vs. 4.4 +/- 0.92 microg/mL, p < 0.01), but not significantly different from noninfected patients. The percentage of monocytes expressing mCD14 in trauma patients did not differentiate them from normal controls; however, mCD14 receptor density did demonstrate significance in septic trauma patients (n = 15) versus normal controls on posttrauma day 3 (p = 0.0065). On the basis of our data, mCD14 did not differentiate infected and noninfected trauma patients, although trauma in general reduced mCD14 and elevated sCD14. Interestingly, 100% of patients who exceeded plasma levels of 8 microg/mL of sCD14 on day 1 after injury developed infections. Therefore, early high expressers of sCD14 may be at higher risk for infectious complications after trauma.

Carboxyhemoglobin elevation in trauma victims.

Products of the hemeoxygenase enzyme include carboxyhemoglobin (COH) and bilirubin, which have protective effects in stressed states. Hemeoxygenase-1 enzyme up-regulates in states of oxidative stress. We hypothesized that COH is elevated in septic trauma patients compared with nonseptic patients. A prospective study was carried out at a Level I trauma center involving all patients admitted to the trauma intensive care unit. During a 3.5-month period, 45 patients were enrolled, with 76 samples being drawn on admission and at later time points. The samples were classified as septic (Bone's criteria), stressed (based on expired gas analysis), or nonstressed nonseptic. Correlations with Acute Physiology and Chronic Health Evaluation III score, white blood cell count, temperature, partial pressure of oxygen, and percentage of inspired oxygen were evaluated. COH levels in samples drawn from patients presenting in shock (systolic blood pressure < or =90 mm Hg) were significantly higher than levels in samples from patients not in shock (systolic blood pressure >90 mm Hg) (3.27+/-1.09 vs. 2.75+/-0.64; p = 0.013). Samples from septic patients with infection were associated with significantly higher Injury Severity Scores (34.1+/-11.2 vs. 21.8+/-18.3; p< or =0.05) and a lower percentage of inspired oxygen (41.6+/-10.3 vs. 61.0+/-26.3; p< or =0.05). COH was significantly elevated in samples drawn during stress, sepsis, and shock states. There was overlap between sepsis and stress COH sample values, limiting the clinical usefulness of the assays in predicting sepsis. Further studies focusing on hemeoxygenase-1 expression and the role of its by-products in the outcomes of trauma patients are warranted.

Clinical significance of antibiotic endotoxin-releasing properties in trauma patients.

To test the hypothesis that antibiotics leading to greater endotoxin release are associated with greater mortality in septic trauma patients. Post hoc analysis of data from a previously conducted prospective, randomized, multicenter study designed to evaluate the efficacy of interferon gamma in preventing infection and death in trauma patients. Nine level I trauma centers. Severely injured trauma patients at high risk for sepsis. Eighty percent (N = 334) of the enrolled patients developed some manifestation of gram-negative sepsis, defined by the administration of gram-negative specific antibiotics. The in-hospital mortality rate of patients who received penicillin-binding protein 3/tumor necrosis factor (PBP3/TNF)-specific antibiotics associated with the greatest degree of endotoxin release and TNF production (PBP3/TNF group, n = 78: aztreonam, ceftazidime, and cefotaxime sodium) was compared with that of patients not receiving these agents (non-PBP3/TNF group, n = 256). Mortality in the PBP3/TNF group (17%) was higher than in the non-PBP3/TNF group (8%, P = .02). The two groups were similar in their mean (+/- SD) Injury Severity Scores (34 +/- 9), ages (31 +/- 12 years), and initial degree of bacterial contamination. Antibiotics that are associated with greater release of endotoxin and production of TNF are also associated with greater mortality in septic trauma patients. Decisions regarding antibiotic administration may need to consider the endotoxin-releasing properties of antibiotics in addition to their antibacterial sensitivity spectrum. Prospective studies of the effect of endotoxin-releasing properties of antibiotics on mortality are warranted.