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Human microbiota demonstrate diversity and balance that is adaptive for the host and supports maintaining homeostasis. Although acute illness or injury may derange microbiota diversity and the proportion of potentially pathogenic microbes, that derangement may be further exacerbated by commonly deployed intensive care unit (ICU) therapeutic and practices. These include antibiotic administration, delayed luminal nutrition, acid suppression, and vasopressor infusion. Furthermore, the local ICU microbial ecology, regardless of disinfection practices, shapes the patient's microbiota, especially with the acquisition of multi-drug-resistant pathogens. Current approaches to protect a normal microbiome, or restore a deranged one, are part of a multifaceted approach that may include antibiotic stewardship and infection control practices as microbiome-directed therapeutics emerge.

Background: Previous estimates of the incidence of necrotizing soft tissue infections (NSTI) in the United States have substantial limitations and underestimate its occurrence. Improvements in hospital mortality after NSTI have increased the number of survivors at risk for long-term sequelae. This study estimates the incidence of NSTI and the burden of re-admission and associated healthcare spending in patients who survived admission for NSTI. Methods: Index admissions for NSTI were identified using International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes combined with either Current Procedural Technology (CPT) or diagnosis-related group codes to increase specificity. Two separate datasets were used to provide primary and secondary estimates of the annual incidence of NSTIs in the United States: the National Inpatient Sample (NIS) for the years 2012-2016 and the Watson Health dataset for 2009-2013, respectively, and extrapolated to estimate the incidence for 2018. The Nationwide Readmissions Database (NRD) from 2013-2015 was used to estimate of the risk for re-admission, cost of re-admissions, and to compare 90-day re-admission rates for NSTI to common medical conditions. Results: National Inpatient Sample and Watson Health datasets demonstrated an increasing annual incidence and estimated 33,600 and 28,500 cases in 2018, respectively. The estimated annual incidences in the United States in 2018 were 10.3 and 8.7 per 100,000 persons, respectively. Risk of 90-day re-admission ranged from 24%-29% over the 3 years, 89% of which were unplanned. Of those re-admitted, 90% had one or more comorbidities, the most common diagnoses associated with re-admission were infection in 65%, acute kidney injury in 22%, and shock in 10%. The median re-admission length of stay was seven days (interquartile range [IQR]: 4-13 days) with a median cost of re-admission of $13,590 (IQR: $7186-$27440). Conclusion: The incidence of NSTI is more common than generally reported. Re-admission within 90 days is common, occurring in more than one in four survivors resulting in high healthcare costs.

Background: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)-associated viral infection (coronavirus disease 2019, COVID-19) is a virulent, contagious viral pandemic that is affecting populations worldwide. As with any airborne viral respiratory infection, surgical and non-surgical patients may be affected. Methods: Review and synthesis of pertinent English-language literature pertaining to COVID-19 infection among adult patients. Results: COVID-19 disease that requires hospitalization results in critical illness approximately 25% of the time and requires mechanical ventilation with positive airway pressure. Acute kidney injury, a marked hypercoagulable state, and sometimes myocarditis can be features of COVID-19 in addition to the characteristic severe acute lung injury. Even if not among the most seriously afflicted, older patients with medical comorbidities are both predisposed to infection and risk increased morbidity and mortality, however, all persons presenting for surgical intervention should be suspected of infection (and thus transmissibility) even if asymptomatic. Although most elective surgery has been curtailed by administrative or governmental fiat, patients will still need urgent or emergency operative intervention for time-sensitive disease processes such as malignant neoplasia or for true emergencies such as perforated viscus or traumatic injury. It is possible to provide safe surgical care for SARS-CoV-2-positive patients and minimize nosocomial transmission to healthcare workers. Conclusions: This guidance will facilitate appropriate protection of patients and staff, and maintenance of infection control measures to assist surgical personnel and facilities to prepare for COVID-19-infected adult patients requiring urgent or emergent operative intervention and to provide optimal patient care.

Background: Surgical research is potentially invasive, high-risk, and costly. Research that advances medical dogma must justify both its ends and its means. Although ethical questions do not always have simple answers, it is critically important for the clinician, researcher, and patient to approach these dilemmas and surgical research in a thoughtful, conscientious manner. Methods: We present four ethical issues in surgical research and discuss the opposing viewpoints. These topics were presented and discussed at the 39th Annual Meeting of the Surgical Infection Society as pro-con debates. The presenters of each opinion developed a succinct summary of their respective reviews for this publication. Results: The key subjects for these pro-con debates were: (1) Should patients be enrolled for time-sensitive surgical infection research using an opt-out or an opt-in strategy? (2) Should patients who are being enrolled in a randomized controlled trial (RCT) comparing surgery with a non-operative intervention pay the costs of their treatment arm? (3) Should the scientific community embrace open access journals as the future of scientific publishing? (4) Should the majority of funding go to clinical or basic science research? Important points were illustrated in each of the pro-con presentations and illustrated the difficulties that are facing the performance and payment of infection research in the future. Conclusions: Surgical research is ethically complex, with conflicting demands between individual patients, society, and healthcare economics. At present, there are no clear answers to these and the many other ethical issues facing research in the future. Answers will only come from continued robust dialogue among all stakeholders in surgical research.

Background: Ventilator-associated pneumonia (VAP) is common in critically injured patients. The pathogenesis of VAP is not completely understood. We hypothesized that mechanically ventilated trauma patients who develop pneumonia have a progressive increase in pathogen burden over the course of ventilation until a threshold for symptomatic pneumonia is reached, leading to clinical suspicion of VAP., Methods: Critically injured adults ventilated for more than two successive days were enrolled. Patients underwent daily surveillance mini-bronchoscopic alveolar lavage (mBAL) while ventilated for 14 days or until extubation. Standard semi-quantitative cultures were performed, and the investigators were blinded to the results. Standard patient management was performed by the clinical team. Patients suspected of having VAP by the clinical team underwent bronchoscopic bronchoalveolar lavage (bBAL) and semi-quantitative culture, with VAP defined as clinical symptoms plus >10 4 colony-forming units (CFU) of bacteria. Standard statistical analysis for non-parametric data was performed., Results: The 37 patients enrolled were ventilated for a median of nine days. While ventilated, 23 patients met the criteria for a clinical suspicion of VAP, of which two were too ill for bronchoscopy. Thus, 21 patients underwent bBALs because of a suspicion of VAP, and 13 (35%) were positive, with >10 4 CFU of one or more pathogens, and were treated for pneumonia. The bacterial burden on mBAL remained <10 4 CFU during ventilation for 32% of patients. None developed clinical symptoms of VAP. Two-thirds (67%) had an mBAL bacterial burden of >10 4 CFU without clinical suspicion of VAP. Half (56%) of positive surveillance cultures were followed by clinical VAP, confirmed by bBAL, all of which had identical pathogens on mBAL and bBAL. Almost half (44%) of the patients with positive surveillance mBALs never developed clinical VAP., Conclusion: A significant percentage of critically injured, ventilated adults develop high bacterial burdens in the lungs early in their course, and many clear these bacteria without developing VAP. Further study is needed to identify the factors causing progression to VAP.

Background: The optimal duration of antimicrobial therapy for treatment of complicated intra-abdominal infections (cIAI) in critically ill surgical patients is unknown. Recent evidence suggests that a short (four-day) course of therapy may be effective, however data in severely critically ill patients are limited., Patients and Methods: A single-center, retrospective, cohort study was conducted at a tertiary academic medical center. Adult patients admitted to the surgical intensive care unit (SICU) with cIAI between December 2011 and July 2015 were enrolled. Patients undergoing transplantation and those with less than 24 h in the SICU were excluded. Patients were divided into two groups, short (≤ 7 d) and long (> 7 d) antimicrobial therapy. The primary outcome was treatment failure, which was defined as a composite of recurrent cIAI, secondary extra-abdominal infection, and/or in-hospital mortality from any cause. Categorical and continuous data were analyzed with χ 2 and Mann-Whitney U tests, respectively. Binary logistic regression was performed to determine factors associated with treatment failure and mortality., Results: Of 1,679 patients screened, 240 were included, 103 in the short and 137 in the long group. Patients in the short and long groups received a median of 5 and 14 d of therapy, respectively (p < 0.001). Treatment failure occurred less frequently with a short duration of therapy (39% versus 63%, p < 0.001) and it occurred two days sooner after source control in patients receiving the shorter courses of antimicrobial therapy (short, median 6 d, interquartile range [IQR] 3-9; long, 8 d, IQR 6-14; p < 0.001). Logistic regression demonstrated that a long duration of therapy was associated with treatment failure (odds ratio [OR] 2.186, 95% confidence interval [CI] 1.251-3.820, p = 0.006), but not with mortality (OR 0.738, 95% CI 0.329-1.655, p = 0.461)., Conclusions: In critically ill surgical patients with cIAI, a short duration of antimicrobial therapy after source control resulted in similar outcomes to previously published studies, providing support for the safety of this approach in critically ill patients.

Background: Previous evidence-based guidelines on the management of intra-abdominal infection (IAI) were published by the Surgical Infection Society (SIS) in 1992, 2002, and 2010. At the time the most recent guideline was released, the plan was to update the guideline every five years to ensure the timeliness and appropriateness of the recommendations., Methods: Based on the previous guidelines, the task force outlined a number of topics related to the treatment of patients with IAI and then developed key questions on these various topics. All questions were approached using general and specific literature searches, focusing on articles and other information published since 2008. These publications and additional materials published before 2008 were reviewed by the task force as a whole or by individual subgroups as to relevance to individual questions. Recommendations were developed by a process of iterative consensus, with all task force members voting to accept or reject each recommendation. Grading was based on the GRADE (Grades of Recommendation Assessment, Development, and Evaluation) system; the quality of the evidence was graded as high, moderate, or weak, and the strength of the recommendation was graded as strong or weak. Review of the document was performed by members of the SIS who were not on the task force. After responses were made to all critiques, the document was approved as an official guideline of the SIS by the Executive Council., Results: This guideline summarizes the current recommendations developed by the task force on the treatment of patients who have IAI. Evidence-based recommendations have been made regarding risk assessment in individual patients; source control; the timing, selection, and duration of antimicrobial therapy; and suggested approaches to patients who fail initial therapy. Additional recommendations related to the treatment of pediatric patients with IAI have been included., Summary: The current recommendations of the SIS regarding the treatment of patients with IAI are provided in this guideline.

Despite current antimicrobial stewardship programs (ASPs) being advocated by infectious disease specialists and discussed by national and international policy makers, ASPs coverage remains limited to only certain hospitals as well as specific service lines within hospitals. The ASPs incorporate a variety of strategies to optimize antimicrobial agent use in the hospital, yet the exact set of interventions essential to ASP success remains unknown. Promotion of ASPs across clinical practice is crucial to their success to ensure standardization of antimicrobial agent use within an institution. To effectively accomplish this standardization, providers who actively engage in antimicrobial agent prescribing should participate in the establishment and support of these programs. Hence, surgeons need to play a major role in these collaborations. Surgeons must be aware that judicious antibiotic utilization is an integral part of any stewardship program and necessary to maximize clinical cure and minimize emergence of antimicrobial resistance. The battle against antibiotic resistance should be fought by all healthcare professionals. If surgeons around the world participate in this global fight and demonstrate awareness of the major problem of antimicrobial resistance, they will be pivotal leaders. If surgeons fail to actively engage and use antibiotics judiciously, they will find themselves deprived of the autonomy to treat their patients., Competing Interests: Author Disclosure Statement Dr. Mazuski has received research support from Astra-Zeneca, Bayer, and Merck, and honoraria as an advisory board member, consultant, or speaker from Allergan, Astra-Zeneca, Bayer, and Merck. Dr. Mazuski receives grant support from the National Institutes of Health for collaborative work on an infection control research project. He serves as the President of the Surgical Infection Society without compensation. For the remaining authors, no competing financial interests exist.

Background: Appropriate empiric antibiotic therapy for ventilator-associated pneumonia improves outcomes. Controversy exists regarding the inclusion of aminoglycosides in empiric therapeutic regimens., Methods: The Ovid and Cochrane databases were searched for relevant literature regarding the use of aminoglycosides in combination therapy for ventilator-associated pneumonia. The data supporting the use of aminoglycosides in certain populations and strategies to limit toxicity are summarized., Results: In patients at high risk of infection with antibiotic-resistant gram-negative bacilli and in those with severe illness, aminoglycosides improve clinical outcomes. In critically ill populations, short-duration therapy and high-dose extended-interval dosing of aminoglycosides can improve therapeutic efficacy while limiting nephrotoxicity., Conclusions: In selected populations using appropriate dosing strategies, aminoglycosides should be considered for empiric treatment of ventilator-associated pneumonia.

Purpose: Changes in insulin resistance (IR) cause stress-induced hyperglycemia after trauma, but the numerous factors involved in IR have not been delineated clearly. We hypothesized that a statistical model could help determine the relative contribution of different clinical co-variates to IR in critically injured patients., Patients and Methods: We retrospectively studied 726 critically injured patients managed with a computer-assisted glycemic protocol at an academic level I trauma center (639 ventilated controls without pneumonia (VWP) and 87 patients with ventilator-associated pneumonia (VAP). Linear regression using age, gender, body mass index (BMI), diabetes mellitus, pneumonia, and glycemic provision was used to estimate M, a marker of IR that incorporates both the serum blood glucose concentration (BG) and insulin dose., Results: Increasing M (p<0.001) was associated with age (1.62%; 95% confidence interval [CI] 1.27%-1.97% per decade), male gender (9.78%; 95% CI 8.28%-12.6%), BMI (4.32% [95% CI 4.02%-4.62%] per 5 points), diabetes mellitus (21.2%; 95% CI 19.2%-23.2%), pneumonia (10.9%; 95% CI 9.31%-12.6%), and glycemic provision (27.3% [95% CI 6.6%-28.1%] per 100 g of glucose). Total parenteral nutrition was associated with a decrease in M of 10.3%; 95% CI 8.52%-12.1%; p<0.001., Conclusions: Clinical factors can be used to construct a model of IR. Prospective validation might enable early detection and treatment of infection or other conditions associated with increased IR.

Background: Hyperglycemia caused by stress-induced insulin resistance is associated with both infection and mortality in critically injured patients. The onset of infection may increase stress-induced insulin resistance, leading to hyperglycemia. Hyperglycemia has been shown to precede the diagnosis of ventilator-associated pneumonia (VAP) in critically injured adults and has been suggested to have potential diagnostic importance. However, glycemic control (GC) protocols in critically ill patients limit the development of hyperglycemia despite increasing insulin resistance. Our computer-assisted GC protocol achieves excellent GC, limiting infection-related hyperglycemia while capturing prospectively all glucose values, insulin infusion rates, and the multiplier (M) used to calculate the insulin rate. We hypothesized that surrogate measures of insulin resistance, the insulin infusion rate and multiplier M, would increase prior to the clinical suspicion of VAP, even in euglycemic critically injured patients., Methods: All critically injured patients (2,656) on the computerized glycemic control protocol were included in the analysis and categorized by those developing VAP and those without pneumonia on days 3-10 of their intensive care unit (ICU) stay. Median blood glucose concentration (BG), insulin infusion rate (IDR), and multiplier (M) [Insulin Drip Rate=M*(BG-60)] were determined for VAP patients (n=329) and non-infected ventilated (NIV) patients (n=2,327) on each day of mechanical ventilation. The day of VAP diagnosis according to U.S. Centers for Disease Control and Prevention (CDC) criteria was defined as day zero and VAP patients matched with NIV patients according to ventilator day from -10 to +10. Comparisons were conducted using the Mann-Whitney U test., Results: Baseline characteristics between VAP and NIV groups did not differ. Measures of insulin resistance increased from the time of injury in both groups. Patients with VAP had significantly greater change in both measures of insulin resistance, IDR and M, in the 48 hours preceding the diagnosis of VAP. These changes occurred despite the fact that the computer-assisted GC protocol achieved lower glucose values in VAP patients for the majority of study days., Conclusions: Measures of insulin resistance increase in the two days prior to the clinical suspicion of VAP for critically injured patients on the GC protocol. These changes occur despite the protocol maintaining euglycemia. This data suggests that markers of insulin resistance may provide clinically useful information in the early diagnosis of VAP.

Background: Recent data highlight the educational, financial, and healthcare benefits of acute care surgery (ACS). These data serve as the impetus to create ACS fellowships, which now are accredited by the American Association for the Surgery of Trauma. However, the core components of a curriculum fundamental for ACS training and that yield competence and proficiency have yet to be determined., Methods: Experts in ACS from the United States (n=86) were asked to propose topics in surgical infectious diseases of potential importance in developing a core curriculum for ACS fellowship training. They were then required to rank these topics in order of importance to identify those considered most fundamental., Results: Thirty-one filters ranking in the highest tertile are proposed as topics of surgical infectious diseases that are fundamental to any curriculum of ACS fellowship training. The majority pertains to aspects of thoracic infections (n=8), although topics of soft tissue infections (n=5) comprised four of the top 10 (40%) filters. Abdominal infections (n=6), the biology of sepsis (n=6), and risk, prevention, and prophylaxis (n=6) completed the list., Conclusion: This study identifies the most important topics of surgical infectious disease that merit consideration for incorporation into a core curriculum of ACS training. Hopefully, this information will assist in the development of ACS fellowships that optimize the training of future ACS surgeons.

Background: Hyperglycemia is common in surgical patients and is associated with adverse outcomes. Conflicting data exist regarding the best method and the value of glycemic control in various patient populations. The contributions to hyperglycemia and the components of its control are complex and overlapping and likely contribute to the documented variation in outcomes. We provide an overview of the physiologic contributors to hyperglycemia and its control, review the differences in the major randomized trial results, and summarize the data regarding glycemic control in surgical patients., Methods: Major reviews of the pathophysiology of hyperglycemia in surgical patients, large randomized trials in critically ill and peri-operative populations, and meta-analyses were reviewed. Summations are provided for the critically ill population and for the peri-operative group., Results: A substantial physiologic rationale exists for the control of hyperglycemia in surgical patients during critical illness and in the peri-operative period. Randomized, controlled studies are limited predominately to critically ill populations. The data support controlling hyperglycemia to a serum glucose concentration <200 mg/dL, but the absolute target range remains controversial and studied inadequately. The data indicate the benefit of tight glycemic control using insulin to achieve a target of 80-110 mg/dL (intensive insulin therapy [IIT]) vs. a liberal target of 180-200 mg/dL in critically ill surgical patients, although hypoglycemia is more common with IIT. Inadequate studies are available in the peri-operative period to draw conclusions about non-critically ill surgical patients, but the weight of the data suggests control to < 200 mg/dL likely is beneficial., Conclusions: Surgical patients benefit from maintaining serum glucose concentrations <200 mg/dL. Intensive insulin therapy (80-110 mg/dL), which appears beneficial in critically ill surgical patients but requires frequent measurement of glucose to avoid hypoglycemia. Further studies are needed to determine the appropriate target range and the influence of nutritional provision and other factors on outcome.

Background: The Surgical Infection Society Guidelines for the treatment of complicated skin and soft tissue infections (SSTIs) were published in October 2009 in Surgical Infections, and an overview of these guidelines was provided at the Thirtieth Annual Meeting of the Society. A summary of this overview is provided., Methods: Review of relevant papers related to complicated SSTIs published between 1966 and 2008 with graded recommendations and summations of general epidemiology and recommendations., Results: The frequency of SSTI has increased over the past decade, predominately because of an increase in infections caused by community-acquired methicillin-resistant Staphylococcus aureus. Drug resistance is increasing among all pathogens. A total of 61 graded recommendations were made in the complete guidelines, 28 of which are presented here, separated into those for non-necrotizing and necrotizing infections., Conclusions: Appropriate antibiotic therapy should be provided in complicated SSTIs. Early diagnosis and treatment of necrotizing infections is paramount, as time to therapy alters morbidity and mortality rates.

Background: Group A streptococcal necrotizing soft-tissue infection with toxic shock is a life-threatening disease. Corticosteroid use in the treatment of this process has been reported rarely., Method: Case reports and review of pertinent literature., Results: Two infections caused by the same clonal strain of Streptococcus pyogenes are presented., Conclusion: The cases illustrate the possible utility of high-dose steroids in the treatment of this process.

Background: Resistance to broad-spectrum antibiotics by gram-negative organisms is increasing. Resistance demands more resource utilization and is associated with patient morbidity and death. We describe the implementation of infection reduction protocols, including antibiotic stewardship, and assess their impact on multi-drug-resistant (MDR) healthcare-acquired gram-negative infections., Methods: Combined infection reduction and antibiotic stewardship protocols were implemented in the surgical and trauma intensive care units at Vanderbilt University Hospital beginning in 2002. The components of the program were: (1) Protocol-specific empiric and therapeutic antibiotics for healthcare-acquired infections; (2) surgical antibiotic prophylaxis protocols; and (3) quarterly rotation/limitation of dual antibiotic classes. Continuous healthcare-acquired infection surveillance was conducted by independent practitioners using National Heath Safety Network criteria. Linear regression analysis was used to estimate trends in MDR gram-negative healthcare-acquired infections., Results: A total of 1,794 gram-negative pathogens were isolated from healthcare-acquired infections during the eight-year observation period. The proportion of healthcare-acquired infections caused by MDR gram-negative pathogens decreased from 37.4% (2001) to 8.5% (2008), whereas the proportion of healthcare-acquired infections caused by pan-sensitive pathogens increased from 34.1% to 53.2%. The rate of total healthcare-associated infections per 1,000 patient-days that were caused by MDR gram-negative pathogens declined by -0.78 per year (95% confidence interval [CI] -1.28, -0.27). The observed rate of healthcare-acquired infections per 1,000 patient days attributable to specific MDR gram-negative pathogens decreased over time: Pseudomonas -0.14 per year (95% CI -0.20, -0.08), Acinetobacter-0.49 per year (95% CI -0.77, -0.22), and Enterobacteriaceae -0.14 per year (95% CI -0.26, -0.03)., Conclusion: Implementation of an antibiotic stewardship protocol as a component of an infection reduction campaign was associated with a decrease in resistant gram-negative healthcare-acquired infections in intensive care units. These results further support widespread implementation of such initiatives.

Background: The rate of vancomycin failure in patients with hospital-acquired pneumonia (HAP) caused by methicillin-resistant Staphylococcus aureus (MRSA) has exceeded 40% in several studies. This observation was attributed initially to the lack of weight-based dosing and targeting of lower trough concentrations. However, a subsequent study demonstrated no additional benefit in patients who achieved trough vancomycin concentrations >15 mg/L compared with patients with concentrations between 5 and 15 mg/L. We sought to identify contributors to vancomycin failure in patients with MRSA HAP., Methods: This was a retrospective study of patients in a surgical intensive care unit with MRSA HAP who received vancomycin between January 1, 2005, and July 31, 2007. Clinical outcomes, microbiological data, prior antibiotic exposure, ventilator days, co-morbidities, and demographics were compared in patients with clinical success and those with treatment failure. Their characteristics were compared using a two-sided Fisher exact test or Mann-Whitney U test, as appropriate for nominal or continuous data., Results: More patients in the treatment failure group had received one or more doses of vancomycin within 90 days leading up to MRSA HAP (84% vs. 47%; p = 0.04). In addition, the duration of prior vancomycin exposure was significantly longer among patients in the treatment failure group (6 vs. 0 days; p < 0.05). There were no statistically significant differences in the percentages of patients who achieved a vancomycin trough concentrations > or =15 mg/dL within the first 48 h (28% vs. 17%; p = 0.69), 72 h (44% vs. 39%; p = 1.0), or 96 h (56% vs. 44%; p = 0.74) after starting treatment. Patients in the failure group had a significantly higher overall mortality rate (32% vs. 0; p = 0.02)., Conclusions: These data suggest that patients who have recent exposure to vancomycin are at high risk for vancomycin failure and may benefit from an appropriate alternative when a diagnosis of MRSA HAP is made.

Evidence-based guidelines for managing patients with intra-abdominal infection were prepared by an Expert Panel of the Surgical Infection Society and the Infectious Diseases Society of America. These updated guidelines replace those previously published in 2002 and 2003. The guidelines are intended for treating patients who either have these infections or may be at risk for them. New information, based on publications from the period 2003-2008, is incorporated into this guideline document. The panel has also added recommendations for managing intra-abdominal infection in children, particularly where such management differs from that of adults; for appendicitis in patients of all ages; and for necrotizing enterocolitis in neonates.

Background: Insulin resistance and hyperglycemia are common in acutely injured patients, and associated with poor outcomes. In the era of tight glucose control, measures of insulin responsiveness (IR) may provide a better indicator of patient status than does the serum glucose concentration. We hypothesized that measures of IR during tight glycemic control protocols are associated with infection and may be more predictive than the serum glucose concentration., Methods: All critically injured, mechanically ventilated patients undergo protocolized tight glycemic control with the aid of a computer-based system that calculates the insulin dose using an adapting multiplier (insulin dose = [blood glucose - 60) x M). Consecutive patients on protocol were studied to identify the incidence of positive sterile-site or quantitative bronchoalveolar lavage cultures (>10(4) colony-forming units/mL). Patients were stratified by presence and number of positive cultures and analyzed by both serum glucose measures and measures of IR (average multiplier and average insulin infusion rate)., Results: During the six-month study period, 356 patients were placed on the tight glycemic control protocol. Of these, 101 patients had 192 positive cultures. Patients with positive cultures required significantly more hourly insulin than those without a positive culture (3.7 vs. 2.8 units/h; p = or<0.001). Logistic regression showed the insulin dose (odds ratio 2.1; 95% confidence interval 1.6, 3.0; p = <0.001) and the adapting multiplier to be independent predictors of the patient having a positive culture among other factors associated with nosocomial infection., Conclusions: Insulin resistance, quantified by hourly insulin dose and median multiplier, confers a higher risk of systemic nosocomial infection. Patients with positive cultures actually had lower admission and median blood glucose values over their intensive care unit stays, highlighting the decreased value of this measure as a predictor of outcome in the setting of tight glucose control. A greater insulin requirement suggesting resistance may be used as a marker of a higher risk of nosocomial infection.

Background: Skin and soft tissue infections (SSTIs) may produce substantial morbidity and mortality rates, particularly those classified as complicated or necrotizing., Objective: To weigh the strength of recommendations using the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) methodology and to provide evidence-based recommendations for diagnosis and management for SSTIs., Data Sources: Computerized identification of published research and review of relevant articles., Study Selection: All published reports on the management of complicated and necrotizing SSTIs were evaluated by an expert panel of members of the Surgical Infection Society according to published guidelines for evidence-based medicine. The quality of the evidence was judged by the GRADE methodology and criteria. Practice surveys, pharmacokinetic studies, and reviews or duplicative publications presenting primary data already considered were excluded from analysis., Data Extraction: Information on demographics, study dates, microbiology findings, antibiotic type, surgical interventions, infection-related outcomes, and the methodologic quality of the studies was extracted. Results were submitted to the Therapeutic Agents Committee of the Surgical Infection Society for review prior to creation of the final consensus document., Data Synthesis: Current surgical and antibiotic management of complicated SSTIs is based on a small number of studies that often have insufficient power to draw well-supported conclusions, with the exception of antimicrobial therapy for non-necrotizing soft tissue infections, for which ample data are available.

Background: Obese patients are at higher than normal risk for postoperative infections such as pneumonia and surgical site infections, but the relation between obesity and infections acquired in the intensive care unit (ICU) is unclear. Our objective was to describe the relation between body mass index (BMI) and site-specific ICU-acquired infection risk in adults., Methods: Secondary analysis of a large, dual-institutional, prospective observational study of critically ill and injured surgical patients remaining in the ICU for at least 48 h. Patients were classified into BMI groups according to the National Heart, Lung and Blood Institute guidelines: or= 40.0 kg/m(2) (severely obese). The primary outcomes were the number and site of ICU-acquired U.S. Centers for Disease Control and Prevention-defined infections. Multivariable logistic and Poisson regression were used to determine age-, sex-, and severity-adjusted odds ratios (ORs) and incidence rate ratios associated with differences in BMI., Results: A total of 2,037 patients had 1,436 infection episodes involving 1,538 sites in a median ICU length of stay of 9 days. After adjusting for age, sex, and illness severity, severe obesity was an independent risk factor for catheter-related (OR 2.2; 95% confidence interval [CI] 1.5, 3.4) and other blood stream infections (OR 3.2; 95% CI 1.9, 5.3). Cultured organisms did not differ by BMI group., Conclusion: Obesity is an independent risk factor for ICU-acquired catheter and blood stream infections. This observation may be explained by the relative difficulty in obtaining venous access in these patients and the reluctance of providers to discontinue established venous catheters in the setting of infection signs or symptoms.

Background: Management of necrotizing skin and soft tissue infections (nSSTI) remains difficult, and the mortality rate has been high. We hypothesized that management of nSSTI by an emergency general surgery (EGS) service would improve outcomes., Methods: Retrospective review of EGS patients with idiopathic nSSTI and comparison with historical controls. Demographic, co-morbidity, laboratory, and surgical data were collected. Non-parametric statistical analysis was used to evaluate differences between survivors and non-survivors. Logistic regression analysis was performed to identify risk factors for the primary outcome measure of death., Results: Fifty-two patients met the inclusion criteria, with five deaths (9.6%). The median time to the operating room (OR) was 8.6 h. The Acute Physiology and Chronic Health Evaluation (APACHE) II score, serum lactic acid concentration, and intensive care unit length of stay were significantly different for non-survivors. The APACHE II score was an independent predictor of death when controlling for age and time to OR., Conclusions: An EGS service was associated with shorter time to OR, which may improve the outcome. Physiologic derangement, as estimated by the APACHE II score, is predictive of death from nSSTI.

Background: Whereas animal models of sepsis demonstrate survival benefits for the pro-estrus state, human observational studies have failed to demonstrate a consistent survival advantage among female patients. Estrogen biosynthesis differs substantially in primate and non-primate animals, and estrogens have diverse immunologic actions. Estrogen concentrations are elevated in response to critical illness and injury (regardless of sex), and elevated concentrations of serum estradiol are associated with a higher mortality rate. Our objective was to determine the predictive ability and test characteristics of the serum estradiol concentration at 48 h in critically ill patients., Methods: A prospective cohort study of surgical and trauma adult intensive care unit patients at two academic tertiary-care centers. Sex hormones (estradiol, progesterone, testosterone, prolactin, and dehydroepiandrosterone) and cytokines were assayed at 48 h, and the 28-day all-cause mortality rate was assessed., Results: There was no difference in mortality rates between the sexes (survivors being male in 75.2% of cases vs. 76.0% in non-survivors; p = 0.43). The serum estradiol concentration was significantly elevated in non-survivors regardless of sex (median 18.7 pg/mL [interquartile range {IRQ} 9.99-43.6] in survivors and 40.7 pg/mL [IQR 9.99-94.8] in non-survivors; p < 0.001). The area under the receiver-operating characteristic (ROC) curve for serum estradiol was 0.64 (95% confidence interval [CI] 0.55, 0.72). The parameter with the largest ROC curve was the Acute Physiology and Chronic Health Evaluation (APACHE) II score (0.75; 95% CI 0.68, 0.82). A serum estradiol cut-point of 50 pg/mL was 48% sensitive and 80% specific in predicting death and classified the outcome of 76% of patients correctly., Conclusions: Serum estradiol concentration is a valuable prognostic tool and potential contributor to adverse outcomes of critically ill or injured surgical patients.

Background: The benefit of antibiotic prophylaxis for intracranial pressure (ICP) monitors remains controversial, and clinical practice varies widely. Whether any antibiotic coverage, particularly broad-spectrum coverage, reduces monitor-related infections remains unproved, and exposure to antibiotics may affect the susceptibility patterns of pathogens producing subsequent infectious complications. Despite the lack of data supporting its use, our level I trauma center had a long-standing ICP monitor prophylaxis protocol that provided broad-spectrum coverage that included ceftriaxone. In April 2002, a protocol change was instituted that substituted cefazolin for ceftriaxone as single-agent prophylaxis for ICP monitors., Hypothesis: Broader-spectrum antibiotic prophylaxis does not reduce ICP monitor-related infections but is associated with acquisition of more drug-resistant infections than narrow-spectrum prophylaxis., Methods: To evaluate the influence of broad- versus narrow-spectrum prophylaxis, a three year period encompassing each practice was selected. All injured patients with ICP monitors placed between January 1, 2001, and December 31, 2003 (n = 279), were identified using the Vanderbilt trauma database. Antibiotic prophylaxis for ICP monitors was determined using the hospital financial database to identify all antibiotics given to individual patients and subsequent chart review to identify those antibiotics given solely for ICP prophylaxis. A total of 119 patients received narrow-spectrum (either cefazolin or vancomycin; n = 100) or no (n = 19) prophylaxis, whereas 160 received broad-spectrum prophylaxis (ceftriaxone or ciprofloxacin). The two groups did not differ with respect to baseline demographics, type of ICP monitor, or duration of monitor placement. Infectious complications were determined by continuous infection surveillance utilizing standard U.S. Centers for Disease Control and Prevention National Nosocomial Infection Surveillance System (CDC-NNIS) definitions and maintained in a contemporary database. The influence of broad-spectrum antibiotic prophylaxis on both ICP monitor infections and subsequent infections outside the central nervous system (CNS) was determined., Results: Nine patients (3.2%) developed CNS infections; two of 119 patients (1.7%) who received narrow-spectrum or no prophylaxis versus seven of 160 patients (4.4%) who received broad-spectrum prophylaxis (p = NS). Only the duration of monitor placement and Injury Severity Score were associated with the infection rate. In the total population, 185 infections occurred in 93 patients (33%). Infection rates did not differ between patients who received narrow-spectrum or no prophylaxis (32%) and those who received broad-spectrum prophylaxis (34%). However, patients who received broad-spectrum prophylaxis acquired gram-negative infections with significantly greater antibiotic resistance., Conclusions: Broad-spectrum antibiotic prophylaxis of ICP monitors does not reduce CNS infections, but is associated with a shift to resistant gram-negative pathogens in subsequent infectious complications. Thus, broad-spectrum antibiotic prophylaxis of ICP monitors should be eliminated or minimized unless data from randomized trials prove its utility.

Objective: One of the primary goals of damage control surgery in the trauma patient is primary closure of the abdomen. We hypothesized that extra-abdominal infections, such as those complicating injuries to the thorax, diaphragm, long bones, or musculoskeletal system, would decrease the likelihood of primary abdominal closure and increase hospital resource utilization in patients requiring open abdominal management., Methods: The trauma registry of the American College of Surgeons (TRACS) was reviewed retrospectively from 1995-2002 for open abdomen technique and damage control surgery. The outcome was primary fascial closure or delayed closure. Patients who died prior to closure were excluded. We evaluated infectious complications, including ventilator-associated pneumonia (VAP), blood stream infection (BSI), and surgical site infection (SSI). Other parameters studied were multiple rib fractures, long bone fractures, chest injuries, diaphragm injuries, empyema, and transfusion requirements. Hospital charges were obtained from the hospital administrative database. Univariate, multivariate, and regression analyses were performed to identify the effects of infectious complications on primary abdominal closure, length of stay, total hospital charges, and disposition., Results: Three hundred forty-four patients required the open abdomen technique: 67% received damage control laparotomy and 33% decompression of abdominal compartment syndrome. Two hundred seventy-six patients (80%) went on to abdominal closure of some form and constituted the primary study group. Primary abdominal closure was achieved in 180 (65%) with a mean time to closure of 3.5 days. Ventilator-associated pneumonia, BSI, and SSI were associated with lack of primary closure (p < 0.05). Increased blood transfusions also were associated with failure of primary closure (p < 0.05). Ventilator-associated pneumonia and BSI were associated with significantly greater lengths of stay in the intensive care unit (ICU) (24.2 days vs. 12.6 days and 30.5 days vs. 17.9 days; both p < 0.0001) and significantly greater total hospital charges (232,080 US dollar vs. 142,893 US dollar; 247,440 US dollar vs. 160,940 US dollar; and 264,778 US dollar vs. 170,447 US dollar; all p < 0.001)., Conclusion: Inability to achieve primary abdominal closure was associated with infectious complications (VAP, BSI, and SSI) and large transfusion requirements. Infectious complications also significantly increased ICU utilization and hospital charges. Death was associated with BSI, femur fractures, and large transfusion requirements, whereas infectious complications did not have a significant impact on discharge disposition.

Background: Ischemia-reperfusion (I/R) of remote organs is a common cause of lung injury. We observed that lung injury after partial hepatic I/R in mice coincides with the appearance of 3-nitrotyrosine (NT) in the lung tissue, a marker of peroxynitrite involvement and oxidant stress. Peroxynitrite can cause mitochondrial dysfunction by inactivation of manganese superoxide dismutase (MnSOD), the major antioxidant enzyme in mitochondria. Our aims were to examine whether pulmonary MnSOD is a target of nitration following hepatic I/R and whether nitrated MnSOD (N-MnSOD) correlates with acute lung injury., Methods: Five 20-25-g male C57BL/6 mice underwent laparotomy, and atraumatic occlusion of the portal and arterial blood supply to the upper three lobes of the liver for 90 min. This warm ischemic period was followed by 4 h of reperfusion, and the animals were then euthanized. Lung injury was assessed by LDH and protein levels in bronchoalveolar lavage (BAL) fluid. Pulmonary MnSOD activity in pulmonary homogenates was measured by the cytochrome c reduction method. The presence of N-MnSOD was determined by immunoprecipitation (IP) and Western Blot analysis. Controls (N = 5) underwent sham operation., Results: Elevated plasma transaminases confirmed hepatic injury. Lung injury was demonstrated by elevation in BAL protein and LDH levels (495.7 (48.4) versus 644.9 (37.3) [p < 0.05] and 56.5 (11.8) versus 345.2 (80) [p < 0.01], respectively). Immunoprecipitation and Western blot demonstrated N-MnSOD in the lung tissue of I/R animals but not controls. MnSOD activity decreased following I/R (8.1 (0.7) versus 10.8 (0.3) [p < 0.05])., Conclusions: Pulmonary MnSOD is both nitrated and inactivated following hepatic I/R and is associated with acute lung injury. These findings suggest that MnSOD incapacitance may contribute to I/R-induced lung injury and provide a therapeutic target in attenuating multisystem injury following hepatic I/R.

Background: Critically ill trauma patients are often too unstable for safe transfer to the operating room. Damage control laparotomy patients frequently require early reoperation and have a reported mortality of 50-60%. As a result, many of these patients must undergo laparotomy in the intensive care unit. We hypothesized that patients undergoing bedside laparotomy (BSL) and managed with the abdomen left open would have an unacceptably high mortality or intra-abdominal complications., Methods: We performed a retrospective chart review of our Trauma Registry. Of the 11,096 consecutive trauma admissions from March 1, 1996 to May 20, 2000, 75 patients underwent 95 BSL. Patients were stratified according to injury severity score (ISS), base deficit (BD), lactic acid (LA), total transfusion (TRBC) requirements, indication for BSL, mechanism of injury, infectious complications (intra-abdominal abscess (IAA), fistula), and length of hospital stay., Results: Seventy-five patients underwent 95 BSL. Mean ISS was 50.6 +/- 18.9, mean BD was -11.9 (+/- 5), and the mean LA was 5 +/- 5 for the study group. The TRBC for the group was 43.7 +/- 42.6 units. Indications for the 95 BSL were (1) abdominal compartment syndrome (n = 47, 49.5%); (2) suspected intra-abdominal infection (n = 18, 19.0%); (3) washout/pack removal (n = 14, 14.7%); (4) washout with fascial closure (n = 12, 12.6%); and (5) other (n = 4, 4.2%). Twenty-nine of 75 patients (39.2%; ISS 52.3 +/- 18.8) died within 72 h of operation. Of the 46 remaining patients, an additional eight died 72 h or more after operation, for a late mortality rate of 17.4% and a total mortality rate of 49%. None of these deaths were attributable to either the operation or to post-operative IAA or fistula formation; all late deaths were secondary to multiple organ failure. Intra-abdominal abscesses developed in three of 46 patients (6.5%), each of whom had a TRBC of >100 units (mean, 160 units). Five of 46 patients (10.9%) developed enterocutaneous fistulae. None of these eight patients died. Thirty-eight of 75 patients (50.7%) survived to discharge, with a mean ISS of 40 (+/- 11.9)., Conclusions: Despite the high acuity of the population undergoing BSL, 50.7% of patients survived. Moreover, during BSL, IAA and fistula formation occurred at low rates.