Antibiotic Timing and Progression to Septic Shock Among Patients in the ED With Suspected Infection.

BACKGROUND: Recent medical society opinions have questioned the use of early antimicrobials in patients with sepsis, but without septic shock. RESEARCH QUESTION: Is time from ED presentation to administration of antibiotics associated with progression to septic shock among patients with suspected infection? STUDY DESIGN AND METHODS: This was a retrospective cohort study from March 2007 through March 2020. All adults with suspected infection and first antimicrobial administered within 24 h of triage were included. Patients with shock on presentation were excluded. We performed univariate and multivariate logistic regression analyses predicting progression to septic shock. RESULTS: Seventy-four thousand one hundred fourteen patient encounters were included in the study. Five thousand five hundred ten patients (7.4%) progressed to septic shock. Of the patients who progressed to septic shock, 88% had received antimicrobials within the first 5 h from triage. In the multivariate logistic model, time (in hours) to first antimicrobial administration showed an OR of 1.03 (95% CI, 1.02-1.04; P < .001) for progression to septic shock and 1.02 (95% CI, 0.99-1.04; P = .121) for in-hospital mortality. When adjusted for severity of illness, each hour delayed until initial antimicrobial administration was associated with a 4.0% increase in progression to septic shock for every 1 h up to 24 h from triage. Patients with positive quick Sequential Organ Failure Assessment (qSOFA) results were given antibiotics at an earlier time point than patients with positive systemic inflammatory response syndrome (SIRS) score (0.82 h vs 1.2 h; P < .05). However, median time to septic shock was significantly shorter (P < .05) for patients with positive qSOFA results at triage (11.2 h) compared with patients with positive SIRS score at triage (26 h). INTERPRETATION: Delays in first antimicrobial administration in patients with suspected infection are associated with rapid increases in likelihood of progression to septic shock. Additionally, qSOFA score has higher specificity than SIRS score for predicting septic shock, but is associated with a worse outcome, even when patients receive early antibiotics.

Optimal Antibiotic Duration for Bloodstream Infections Secondary to Intraabdominal Infection.

BACKGROUND: Bloodstream infections (BSIs) secondary to intraabdominal infections (IAIs) are common in the intensive care unit (ICU). The Surgical Infection Society guidelines recommend treatment duration after achieving source control in patients with secondary bacteremia; however, literature supporting this recommendation is limited. The purpose of this study was to compare outcomes in patients who received shorter versus extended duration of antibiotics for bacteremia secondary to IAI. MATERIALS AND METHODS: A retrospective cohort analysis was conducted in adult surgical ICU patients (n = 42) with BSIs and source control procedure(s) for IAI. The primary outcome was recurrent IAI. Secondary outcomes included surgical site infections (SSIs), Clostridium difficile infections (CDIs), secondary fungal infections, and in-hospital mortality. RESULTS: Forty-two patients met inclusion criteria and were divided into groups according to antimicrobial duration; 12 patients received <7 d, and 30 patients received >7 d of antibiotics. There were no differences in baseline characteristics between the two cohorts except for the presence of sepsis [4/12 (33.3%) versus 27/30 (90.0%); P = 0.001]. Thirty-one percent (13/42) of all organisms isolated from blood cultures were gram-negative bacteria, 12/42 (28.6%) were MDROs, and 2/42 (4.8%) patients experienced a culture mismatch in which cultured bacteria were not susceptible to empiric antibiotic therapy. Rates of recurrent IAI were similar between the two cohorts [1/12 (8.3%) versus 4/30 (13.3%), P = 0.554]. CONCLUSIONS: Among surgical ICU patients with BSI secondary to IAI, cessation of antibiotic therapy within 7 d of source control was not associated with an increased incidence of recurrent IAI.

Current progress of source control in the management of intra-abdominal infections.

Intra-abdominal infection (IAI) is a deadly condition in which the outcome is associated with urgent diagnosis, assessment and management, including fluid resuscitation, antibiotic administration while obtaining further laboratory results, attaining precise measurements of hemodynamic status, and pursuing source control. This last item makes abdominal sepsis a unique treatment challenge. Delayed or inadequate source control is an independent predictor of poor outcomes and recognizing source control failure is often difficult or impossible. Further complicating issue in the debate is surrounding the timing, adequacy, and procedures of source control. This review evaluated and summarized the current approach and challenges in IAI management, which are the future research directions.

Temperature-Neutrophils-Multiple Organ Failure Grading for Complicated Intra-Abdominal Infections.

Background: The grading systems for intra-abdominal sepsis (IAS) are not employed commonly in clinical practice because they are too complicated or too specific. We propose to grade IAS with a simple grading system: the TNM system, which is an acronym borrowed from cancer staging, where T indicates Temperature, N indicates Neutrophils, and M indicates Multiple organ failure (MOF). The aim of this prospective observational study is to assess the predictive value of the TNM score on deaths of patients with complicated IAS. Patients and Methods: We considered 147 patients with complicated IAS. Three classes of attribute were chosen: Temperature (T), Neutrophil count (N), and MOF (M). After defining the categories T (T0-T4), N (N0-N3), and M (M0-M2), they were grouped in stages (0-IV). We analyzed specific variables for their possible relation to death: Age, gender, blood transfusion, causes of IAS, T, N, pre-operative organ failure, immunocompromised status, stage 0, I, II, III, and IV. Odds ratios were calculated in a uni-variable and multi-variable analysis. Results: This was the distribution in classes, based on TNM stages: One patient was in stage 0; 15 patients in stage I; 47 patients in stage II; 56 patients in stage III; 28 patients in stage IV. Death occurred in 45 (30.6%) patients. The N, pre-operative organ failure, immunocompromised status, stage III-IV were potential predictors of post-operative death in uni-variable analysis. Only pre-operative organ failure and stage IV were significant independent predictors of post-operative death in multi-variable analysis. Conclusions: The TNM classification is an easy system that could be considered to define the death risk of patients with IAS and to compare patients with sepsis.

[Pathogenesis and classification of advanced peritonitis]. / Patogenez i klassifikatsiia rasprostranennogo peritonita.

The concept of pathogenesis of peritonitis and abdominal sepsis are discussed in the article. Significant scientific findings devoted to this issue occurred in recent years. Nevertheless, there is still no unity in understanding the pathogenesis of peritonitis. Accordingly, the question of its classification is still open. Literature review demonstrates diverse opinions regarding classification of peritonitis. The authors analyze the arguments for and against some classification categories taken on the basis of pathophysiological aspects of this serious complication of abdominal diseases.

What´s new in intraabdominal candidiasis in critically ill patients, a review.

A high prevalence of invasive candidiasis has been reported in recent years. Patients admitted to an intensive care unit are at the highest risk for invasive candidiasis, mostly due to the severity of their disease, immune-suppressive states, prolonged length of stay, broad-spectrum antibiotics, septic shock, and Candida colonization. Intraabdominal candidiasis comprises a range of clinical manifestations, from just the suspicion based on clinical scenario to fever, leukocytosis, increase in biomarkers to the isolation of the responsible microorganism. In critically ill patients with IAC prompt treatment and adequate source control remains the ultimate goal.

[Systemic coagulopathic distress syndrome in surgery: concept, pathogenesis, prophylaxis]. / Ponyatie sistemnogo koagulopaticheskogo distress-sindroma v khirurgii, ego patogenez i printsipy profilaktiki.

OBJECTIVE: The purpose of the study is to determine the correlation of changes in the humoral and tissue components of the hemostasis system with lipid metabolism in case of various urgent surgical diseases, on the basis of which the systemic coagulopathic distress syndrome can be used as the scientific basis for the definition of a new syndrome. MATERIAL AND METHODS: The work includes the results of experimental and clinical laboratory tests. Experiments on dogs: in the first group (n=18) destructive pancreatitis; in the second (n=18) - fecal peritonitis; in the third (n=15), acute obstructive intestinal obstruction; in the fourth (n=16) fecal peritonitis, in the postoperative period, Remaxol (15 ml/kg) was included in the therapy. The analysis of 55 patients with acute peritonitis, operated on for acute appendicitis, perforated gastric or duodenal ulcer, acute intestinal obstruction, acute destructive cholecystitis. In the study group (n=28), Remaxol is included in the postoperative therapy. The state of the humoral and tissue (in the experiment, the tissues of the liver, intestines, kidneys, heart, lungs, pancreas, in the clinic - tissues of the resected organs) components of the hemostasis system was evaluated, a number of lipid metabolism indicators were determined, etc. RESULTS: In the early periods of all investigated urgent diseases of the abdomen, pronounced changes in the system of both humoral and tissue components of the hemostasis system were revealed. The modification of the coagulation system is registered not only in the tissues of the lesion organs, but also in the target organs (system tissue hemocoagulation modifications). The research established one of the most important processes - the trigger of the hemostatic cascade reaction - is membrane-destabilizing (the source of tissue thromboplastin), which is determined by changes in the phospholipid composition of various organs tissues (involved in the pathological process or not in it). Changes in lipid metabolism are due to the activation of phospholipases and membrane lipid peroxidation in tissues. The factual material was the scientific basis for the establishment of a new syndrome. Systemic coagulopathic distress syndrome is a set of pathological processes of the body, the most important component of which is a violation of the phospholipid bilayer of blood cell membranes and organ cells due to oxidative and phospholipase induced phenomena, leading to a coagulopathic condition. It changes understanding of the prevention of thrombohemorrhagic complications, proving the effectiveness of complex therapy, including not only anticoagulants, but also drugs with membrane-stabilizing activity, in particular, Remaxol.

The role of the intra-abdominal view in complicated intra-abdominal infections.

Background: The prognostic role of what a surgeon observes in the abdomen of patients with complicated intra-abdominal infection (cIAI) is largely unknown. The aim of this prospective study was to systemically analyze components of the intra-abdominal view (IAV) and their association to severe complicated intra-abdominal sepsis (SCIAS) or mortality. Methods: The study cohort consisted of adult patients with cIAI. The operating surgeon filled a paper form describing the intra-abdominal view. Demographics, operative details, and preoperative physiological status were collected. Descriptive, univariate, and multivariate statistical analyses were performed, and a new score was developed based on regression coefficients. The primary outcome was a composite outcome of SCIAS or 30-day mortality, in which SCIAS was defined as organ dysfunctions requiring intensive care unit admission. Results: A total of 283 patients were analyzed. The primary outcome was encountered in 71 (25%) patients. In the IAV, independent risk factors for the primary outcome were fecal or bile as exudate (odds ratio (OR) 1.98, 95% confidence interval 1.05-3.73), diffuse peritonitis (OR 2.15, 1.02-4.55), diffuse substantial redness of the peritoneum (OR 5.73, 2.12-15.44), and a non-appendiceal source of cIAI (OR 11.20, 4.11-30.54). Based on these factors, an IAV score was developed and its performance analyzed. The area under the receiver operating characteristic for the IAV score was 0.81. The IAV score also correlated significantly with several outcomes and organ dysfunctions. Conclusions: The extent of peritonitis, diffuse substantial redness of the peritoneum, type of exudate, and source of infection associate independently with SCIAS or mortality. A high IAV score associates with mortality and organ dysfunctions, yet it needs further external validation. Combining components of IAV into comprehensive scoring systems for cIAI patients may provide additional value compared to the current scoring systems. Trial registration: The study protocol was retrospectively registered on April 4, 2016, right after the first enrolled patient at Clinicaltrials.gov database (NCT02726932).

Evaluation of Diaphragmatic Ultrasound Indices as Predictors of Successful Liberation From Mechanical Ventilation in Subjects With Abdominal Sepsis.

BACKGROUND: Sepsis-induced diaphragmatic dysfunction is one of the main risk factors of failure to liberate patients from mechanical ventilation. Several studies addressed diaphragmatic ultrasound as a valuable tool in the assessment of diaphragmatic function during liberation from mechanical ventilation in different populations. However, none of these studies examined the use of diaphragmatic ultrasound to predict failure of liberation from mechanical ventilation in subjects with sepsis METHODS: A prospective observational study was done with subjects on mechanical ventilation and with abdominal sepsis. The diaphragmatic thickening fraction, diaphragmatic excursion, and rapid shallow breathing index were assessed 30 min after a spontaneous breathing trial RESULTS: Thirty subjects were enrolled in the study. Seventeen subjects were successfully extubated (56.6%), whereas extubation failed in 13 subjects (43.4%). The time to the first liberation attempt was significantly shorter in the liberation-success group 2.3 (0.7) d compared with the liberation-failure group 5.8 (4.7) d; P = .02. The optimum cutoff value of diaphragmatic thickening fraction for predicting liberation success was ≥30.7%, with a sensitivity of 94.1% and a specificity of 100%. The area under the curve was 0.977. Although diaphragmatic excursion of ≥10.4 mm had a sensitivity of 94% and a specificity of 85% for predicting liberation success, with an area under the curve of 0.85. A rapid shallow breathing index of ≤44 had a specificity of 100% and a sensitivity of 76%; the area under the curve was 0.9. CONCLUSIONS: Diaphragmatic ultrasound indices, namely diaphragmatic thickening fraction and diaphragmatic excursion, could be useful parameters for assessment of success of liberation in patients on mechanical ventilation with abdominal sepsis. (ClinicalTrials.gov registration NCT03094299.).

Intact Glycocalyx of Intestinal Mucosa in Intraabdominal Infection: an Investigation Using Blood Group Antigen.

BACKGROUND: intestinal glycocalyx plays a role in bacterial translocation as the pathogenesis sepsis derived from intra-abdominal infections that vulnerable in certain blood types. However, the link between intestinal glycocalyx in specific types of blood groups and abdominal infections remains unknown. This study aims to find out the condition of intestinal glycocalyx in certain blood types with intraabdominal sepsis. METHODS: descriptive study involved subjects with intraabdominal infections who underwent laparotomy. Samples are in the form of intestinal specimens. The measurement of intestinal glycocalyx proceeded by the ELISA method using blood group antigens (A and B). Expression data on the secretors were analyzed using the Kolmogorov - Smirnov test followed by parametric comparisons using ANOVA and t-tests. RESULTS: there were 32 subjects with intra-abdominal infections studied in this study. All of them are secretors and express A and B antigens strongly. We found no difference between intraabdominal infections in those with complications or without complications. Blood type O is a predominant blood type found (43.8%). Escherichia coli is the most commonly found microbe in the culture (61.3%). CONCLUSION: this study shows there is no disrupted intestinal glycocalyx of sepsis patients caused by intraabdominal infection.

Clinical practice guidelines in complicated intra-abdominal infection 2018: an Indonesian perspective

BACKGROUND: The occurrence of complicated intra-abdominal infections (cIAI) remains high despite system improvement in accordance with Joint Commission International because of heterogeneity of management. However, published clinical practice guidelines (CPGs) were not feasible to be implemented because these guidelines were not specific to Indonesian characteristics. Thus, a national CPG should be developed to minimize heterogeneity in the management of cIAI in Indonesia. METHODS: We developed a CPG on cIAI through the adaptation of published CPGs. The process proceeded in steps recommended by ADAPTE. Published CPGs were critically appraised using Appraisal of Guidelines for Research and Evaluation (AGREE) II critical appraisal tools. For a specific updated CPG, the analysis was performed using Checklist for the Reporting of Updated Guidelines (CheckUp). Appropriate statements and recommendations in selected CPGs were adapted into our CPG with consideration of Indonesian characteristics. The recommendations were established by the hierarchy of evidence on Grading of Recommendations Assessment, Development and Evaluation (GRADE). The approval of the recommendation draft was performed using the Delphi method. RESULTS: Sixty-eight full-text guidelines were downloaded from several sites. Thirty-three CPGs were related to intra-abdominal infection and 18 others were specific on CPG on intra-abdominal infection and cIAI. On review of these 18 CPGs, 13 were strongly recommended, three were recommended, and two were not recommended. On review updated CPGs, five updated CPGs were found, all with the same score. Two of the strongly recommended updated CPGs had been published in 2016 and 2017, i.e. recommendations by the World Society of Emergency Surgery 2016 consensus conference and revised CPG of the Surgical Site Infection Society. There were a total of 84 statements and recommendations developed and approved by the task force through using the Delphi method. CONCLUSIONS: This guideline summarizes the definition, classification, pathophysiology, etiology, risk factors, assessments, and management of cIAI. Evidence-based recommendations have been developed with consideration of Indonesian-specific characteristics.

Identification of Specific Components of the Eicosanoid Biosynthetic and Signaling Pathway Involved in Pathological Inflammation during Intra-abdominal Infection with Candida albicans and Staphylococcus aureus.

Polymicrobial intra-abdominal infections (IAIs) are a significant cause of morbidity and mortality, particularly when fungal pathogens are involved. Our experimental murine model of IAI involving intraperitoneal inoculation of Candida albicans and Staphylococcus aureus results in synergistic lethality (∼80%) due to exacerbated inflammation. Monomicrobial infection results in no mortality, despite a microbial burden and dissemination similar to those in a coinfection. In the coinfection model, the immunomodulatory eicosanoid prostaglandin E2 (PGE2) was determined to be necessary and sufficient to induce mortality, implicating PGE2 as the central mediator of the amplified inflammatory response. The aim of this study was to identify key components of the PGE2 biosynthetic and signaling pathway involved in the inflammatory response and explore whether these can be targeted to prevent or reduce mortality. Using selective pharmacological inhibitors of cyclooxygenases (COX) or PGE2 receptor antagonists in the C. albicans-S. aureus IAI mouse model, we found that inhibition of COX and/or blocking of PGE2 receptor 1 (EP1) or PGE2 receptor 3 (EP3) signaling reduced proinflammatory cytokine production, promoted interleukin-10 production, reduced cellular damage in the peritoneal cavity, and, most importantly, significantly improved survival. The greatest effect on survival was obtained by the simultaneous inhibition of COX-1 activity and EP1 and EP3 receptor signaling. Importantly, early inhibition of PGE2 pathways dramatically improved the survival of fluconazole-treated mice compared with that achieved with fluconazole treatment alone. These findings indicate that COX-1 and the EP1 and EP3 receptors mediate the downstream pathological effects of PGE2 during polymicrobial IAI and may serve as effective therapeutic targets.

[PREDICTORS OF UNFAVORABLE OUTCOME IN PATIENTS WITH ABDOMINAL SEPSIS.]

OBJECTIVE: The study focuses on identifying predictors of treatment outcome in abdominal sepsis (AS) in humans. SUBJECTS AND METHODS: 70 patients underwent determination of blood pressure, heart rate, SpO , the content of leu- kocytes, albumin, C-reactive protein, fibrinogen and TNF-a in arterial (femoral artery) and venous (subclavian vein) blood. Automatic biochemical analyzer Cobas-Integra 400 ('Roche", Switzerland), the test system Microlab STAR ELISA kit reagents "alpha TNF - ELISA - best" were used during the research. System statistical analysis included paired comparison of patients with favorable (n=27) and lethal (n=43) outcome, correlation, cluster; discriminating analysis, multidimensional scaling and plotting ROC curves with sensitivity and specificity indicators predictive value. RESULTS: Identfied predictors of outcome inpatients,from which to form a predictive model of CRP fibrinogen, albumin, and TNF-a arterial blood. It is established that if the basic treatment of the patient CRP <9,8 g/l,fibrinogen >3,43 g/l, albumin <28,9 gl and TNF-a <499,3 ng/ml, the probability of death was statistically significantly higher thanfavorable. CONCLUSION: It is assumed that therapeutic measures should be aimed at correction of the above mentioned indicators.

Abdominal Infection Suppresses the Number and Activity of Intrahepatic Natural Killer Cells and Promotes Tumor Growth in a Murine Liver Metastasis Model.

BACKGROUND: Increasing evidence suggests that postoperative infection is associated with poorer long-term outcome in various malignancies. However, the mechanism of poor prognosis induced by postoperative infection has not been clearly explained. We sought to determine whether abdominal infection promotes cancer metastases in a murine liver metastasis model, and to investigate the role of liver natural killer (NK) cells on antitumor immunity during abdominal infection. METHODS: Female BALB/c (8-10 weeks old) mice were inoculated with NL-17 colon cancer cells into the spleen and then subjected to abdominal infection induced by cecal ligation and puncture (CLP) or sham treatment. The extent of liver metastases and cytokine production in the serum and liver were investigated. Cell fraction and cytotoxic activities of liver mononuclear cells (MNCs) were elucidated. RESULTS: CLP mice had poorer survival and their serum levels of IL-6, -10, and -12p70 were significantly elevated on day 1 compared with sham-treated and control mice. No obvious differences in cytokine levels of the liver homogenates were identified among the three groups, except IL-12p70 levels in CLP mice on day 7 significantly decreased. The cytotoxic activities of liver MNCs were significantly suppressed in CLP mice soon after tumor inoculation. Flow cytometry revealed a decrease in NK cells in the liver and perforin and granzyme B expression levels. CONCLUSIONS: Abdominal infection promoted liver metastases in a murine liver metastasis model, which may be partially caused by a decrease in the number and activity of NK cells during abdominal infection.

The challenge of intra-abdominal sepsis.

UNLABELLED: An overview of intra-abdominal sepsis is necessary at this time with new experimental studies, scoring systems and audits on management outcomes. The understanding of the pathophysiology of the peritoneum in the manifestation of surgical sepsis and the knowledge of the source of pathogenic organisms which reach the peritoneal cavity are crucial in the prevention of intra-abdominal infection. Inter-individual variation in the pattern of mediator release and of end-organ responsiveness may play a significant role in determining the initial physiological response to major sepsis and this in turn may be a key determinant of outcome. The ability to identify the presence of peritoneal inflammation probably has the greatest influence on the final surgical decision. The prevention of the progression of sepsis is by early goal-directed therapy and source control. Recent advances in interventional techniques for peritonitis have significantly reduced the morbidity and mortality of physiologically severe complicated abdominal infection. In the critically ill patients there is some evidence that the prevention of gut mucosal acidosis improves outcome. The aim of this review is to ascertain why intra-abdominal sepsis remains a major clinical challenge and how a better understanding of the pathophysiology may enable its prevention and better management. METHOD: Electronic searches of the medline (PubMed) database, Cochrane library, and science citation index were performed to identify original published studies on intra-abdominal sepsis and the current management. Relevant articles were searched from relevant chapters in specialized texts and all included.

The combined effects of glutamine and growth hormone on intestinal anastomosis in the rat intra-abdominal sepsis model.

AIM: Intestinal anastomoses are always risky in patients who develop intra-abdominal sepsis. In this study, the effects of combined glutamine and growth hormone (GH) on healing of intestinal anastomosis following intestinal repair in the rat intra-abdominal sepsis was induced. MATERIAL AND METHODS: Forty Sprague Dawley Albino rats at 10 weeks weighing between 180 and 240 g were included in the study. All the animals were divided into five groups comprising eight rats each. In the control group, no treatment was given in addition to the routine oral nutrition before and after surgery. In the other groups, following surgery, oral glutamine was given at a dose of 1 mg/kg/d in the glutamine group, subcutaneous GH was given at a dose of 1 mg/kg/d in the GH group, and combined glutamine and GH were administered at the same doses in the glutamine + GH group. In rats, a clinical model mimicking intestinal fistula was generated and fistula repair was performed, and the bursting pressure of the repair area and tissue hydroxyproline level of the repair area were calculated. RESULTS: Compared with the control group, glutamine, GH, and combined groups displayed significantly higher mean bursting pressures and tissue hydroxyproline levels. CONCLUSION: In order to decrease the risks originating from impaired mechanisms due to intra-abdominal sepsis, and to make anastomosis safer, combined use of glutamine and GH increases the bursting pressure of anastomosis. While the use of either of these two substances alone is effective, combined use makes this effect more prominent.