Forms Of Sepsis Research Articles

STERNAL WOUND INFECTION AFTER CARDIAC SURGERY: LOOKING FOR INTERACTIONS BETWEEN PERIOPERATIVE VARIABLES AND PATHOGEN AGENTS

Abstract Background Sternal wound infection (SWI) can be a major complication of cardiac surgery. Both the risk factors and the pathogens agents are well known today. Yet, possible interactions between perioperative variables and pathogens have not been explored. Methods Between Jan 1st, 2006 and Nov 30, 2023 (∼18 years), perioperative data of all patients undergoing cardiac operations through median sternotomy at the Cardio–Thoraco–Vascular Department of the University Hospital of Trieste, Italy, were recorded prospectically in a computed database. Every patient developing a sternal complication was followed in a dedicated outpatient clinic and, in the presence of infection, the causative pathogen was always searched for by cultural examination of tissue speciments. Different strategies of unsupervised clustering were applied to find groups of patients with similar clinical, surgical and microbiological profiles. Results Of 9,680 consecutive cardiac surgery patients, 516 (5.3%) experienced a SWI that involved superficial soft tissue in 25.6% of cases, deep soft tissue in 51%, sternal bone in 16.7%, or mediastinum in 6.8% of cases. Staphylococcus aureus, coagulase–negative Staphylococci, Enterobacteriaceae, and Pseudomonas aeruginosa were pathogens in 100 (19.4%), 158 (30.6%), 89 (17.2%) and 36 (7%) patients, respectively; other pathogens, polymicrobial and negative cultures were found in 27 (5.2%), 26 (5%) and 80 (15.5%) patients, respectively. Following statistical analyses, significant associations were found between the Pseudomonas aeruginosa etiology of SWI and some variables such as female gender (p<0.0001) and preoperative renal failure (p=0.008); significant associations between the Pseudomonas aeruginosa etiology were found also with more serious forms of sepsis (p=0.025), as well as with early postoperative death (p=0.02) and complications such as acute kidney injury (p=0.006), multiple transfusion (p=0.003), and prolonged mechanical ventilation (p=0.005). Conclusion For women having renal impairment and undergoing cardiac surgery through median sternotomy, in the case of SWI, the Pseudomonas aeruginosa etiology may be more frequent and a really life–threating complication.

The Role of Procalcitonin in Neonatal Sepsis-examining Facts and Misconceptions

Background: Neonatal sepsis has remained a major cause of neonatal morbidity and mortality. Despite advances in neonatal diagnostics, its diagnosis has remained challenging majorly because its symptoms are vague and blood culture which remains the gold standard for diagnosis is cumbersome and has poor yield and other forms of sepsis are usually not sought for (anaerobes, viral fungal). The search for newer diagnostic methods is still on going and procalcitonin has shown some promise. Aim/Objective: The aim of the study is to examine the role procalcitonin plays in neonatal sepsis. Materials and Methods: A total of 248 neonates with suspicion of sepsis were enrolled and had their samples taken for blood culture, full blood count, C-reactive and procalcitonin assay based on which the neonates were classified as proven, suspected and clinical sepsis. Result: The behaviour of procalcitonin in the different sepsis groups (more elevated in proven and suspected than clinical), ages (to accommodate the physiologic variation seen in the first 72hours of life) and according to isolates (more elevated in gram negative than gram positive sepsis). The diagnostic value of procalcitonin was also determined and found have sensitivity 74.5%, specificity 38.3%, positive predictive value 42.4% and negative predictive value 71.1%, which were better after >72hours of life. Conclusion: For now, procalcitonin should continue to serve as a supportive marker for sepsis as its levels are affected by age of the neonate, sepsis mimics, and type of offending organism causing the infection.

PD19-07 A S. HAEMATOBIUM IMMUNOMODULATORY PROTEIN PREVENTS INTRAABDOMINAL SEPSIS

You have accessJournal of UrologyCME1 Apr 2023PD19-07 A S. HAEMATOBIUM IMMUNOMODULATORY PROTEIN PREVENTS INTRAABDOMINAL SEPSIS Ioannis Koutroulis, Wade O'Brien, and Michael Hsieh Ioannis KoutroulisIoannis Koutroulis More articles by this author , Wade O'BrienWade O'Brien More articles by this author , and Michael HsiehMichael Hsieh More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003285.07AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Urinary tract reconstruction with bowel carries risks of bowel leak and resulting sepsis. Even with the current standard of care, sepsis remains a challenging and sometimes life-threatening condition. Urogenital and hepatoenteric schistosomiasis transmission depend upon the successful transit of eggs across the bladder and intestinal walls, respectively. However, egg passage disrupts local tissues and can lead to bacterial translocation, sepsis, and host death, an undesirable outcome for schistosomes that rely on continuous oviposition to maximize reproductive success. There is evidence that schistosomes may immunoregulate their hosts to prevent sepsis. Schistosoma mansoni-infected mice develop endotoxemic sepsis and die if their myeloid cells lack the IL-4 receptor. Mice whose bladders are injected with Schistosoma haematobium eggs also develop endotoxemia and die if phagocytic cells are depleted. Schistosoma eggs secrete large amount of the interleukin-4-inducing principle of S. mansoni eggs (IPSE). These findings led us to hypothesize that IPSE may be a schistosome molecule that prevents host sepsis. METHODS: To test this hypothesis, mice underwent intraperitoneal injection with cecal slurry to induce sepsis. They then received intravenous IPSE or vehicle injection immediately or 1 hour post-sepsis induction with cecal slurry injection. Mice were then assigned clinical sepsis scores every 2 hours for 18 hours in a blinded fashion (maximum score of 28). RESULTS: Both mouse groups (treated vs. non-treated) had similar baseline scores. Whereas mice given vehicle injections developed progressively severe sepsis (15-18), IPSE-treated mice immediately after cecal slurry injection did not exceed a score of 16 at any time point. Additionally, at time of euthanasia (18 hours post-sepsis induction), there was a decrease in average sepsis scores in the IPSE-treated group compared to vehicle-treated mice, that continued to have a worsening clinical course. A 48-plex cytokine analysis of mouse plasma collected at time of euthanasia from mice that were given either IPSE or vehicle 1 hour post-sepsis induction,was performed using the Luminex platform. This revealed significant changes in multiple cytokines, consistent with IPSE’s known immunoregulatory mechanisms. CONCLUSIONS: These findings support the hypothesis that IPSE may prevent schistosomiasis-associated sepsis and suggests that IPSE could be developed as a therapeutic agent for other forms of sepsis. Source of Funding: NIDDK © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e579 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Ioannis Koutroulis More articles by this author Wade O'Brien More articles by this author Michael Hsieh More articles by this author Expand All Advertisement PDF downloadLoading ...

Malnutrition Imparts Worse Outcomes in Patients With Diverticulitis: A Nationwide Inpatient Sample Database Study.

IntroductionStudies show that malnutrition can lead to worsening morbidity and mortality in patients. However, to our knowledge, no large database study has been conducted describing the effects of malnutrition in patients with diverticulitis. In this article, we aim to assess the impact of pre-existing malnutrition on outcomes of patients admitted for diverticulitis.MethodsData between 2008 and 2014 from the Nationwide Inpatient Sample database were extracted. Inclusion criteria for both groups included patients with a primary diagnosis of diverticulitis using the International Classification of Diseases, Ninth Revision codes. Exclusion criteria included all patients less than 18 years of age. The test group consisted of patients with a primary diagnosis of diverticulitis and a concurrent diagnosis of malnutrition. In-hospital mortality, length of stay, total cost, and complications, including various forms of sepsis, perforation, bleeding, and GI bleeding, were compared between the two groups. Univariate and multivariate analyses were used to generate odds ratios. Multivariate analysis included age, sex, race, income quartile, and calculated Elixhauser scores. Elixhauser comorbidity scores predicting mortality and readmission were calculated based on weighted scores from 29 different comorbidities. Scores were compared between the two groups using univariate analysis.ResultsThere were a total of 1,520,919 patients in the study, of which 427,679 (2.8%) had a pre-existing diagnosis of malnutrition. On univariate analysis, there was a significant increase in mortality in patients with malnutrition (OR: 10.2, p < 0.01). Additionally, patients with malnutrition appeared to have longer lengths of stay (mean: 12.9, p < 0.01) and greater cost of hospitalization (mean: 194436.82, p < 0.01). Patients with malnutrition had greater rates of sepsis events (OR: 12.0, p < 0.01), perforation (OR: 2.8, p < 0.01), and GI bleed (OR: 1.84, p < 0.01). On multivariate analysis, malnutrition appeared to significantly increase mortality (OR: 3.3, p < 0.01).DiscussionPatients who present with diverticulitis with malnutrition appear to have significantly worse outcomes. We hypothesize that malnutrition leads to a shift in the gut microbiota, resulting in increased inflammation. As a result, these patients may have an increased risk of worse outcomes, such as sepsis and death. Addressing nutrition in patients with diverticulosis or those with a history of diverticulitis may improve outcomes.This abstract was previously presented at the Digestive Disease Week Conference on May 22, 2022. s accepted at the conference were published in supplements of the journals Gastroenterology and GIE: Gastrointestinal Endoscopy.

Targeting acute kidney injury in COVID-19.

As of 15 August 2020, Coronavirus disease 2019 (COVID-19) has been reported in >21 million people world-wide and is responsible for more than 750,000 deaths. The occurrence of acute kidney injury (AKI) in patients hospitalized with COVID-19 has been reported to be as high as 43%. This is comparable to AKI in other forms of pneumonia requiring hospitalization, as well as in non-infectious conditions like cardiac surgery. The impact of AKI on COVID-19 outcomes is difficult to assess at present but, similar to other forms of sepsis, AKI is strongly associated with hospital mortality. Indeed, mortality is reported to be very low in COVID-19 patients without AKI. Given that AKI contributes to fluid and acid–base imbalances, compromises immune response and may impair resolution of inflammation, it seems likely that AKI contributes to mortality in these patients. The pathophysiologic mechanisms of AKI in COVID-19 are thought to be multifactorial including systemic immune and inflammatory responses induced by viral infection, systemic tissue hypoxia, reduced renal perfusion, endothelial damage and direct epithelial infection with Severe Acute Respiratory Syndrome Coronavirus 2. Mitochondria play a central role in the metabolic deregulation in the adaptive response to the systemic inflammation and are also found to be vital in response to both direct viral damage and tissue reperfusion. These stress conditions are associated with increased glycolysis and reduced fatty acid oxidation. Thus, there is a strong rationale to target AKI for therapy in COVID-19. Furthermore, many approaches that have been developed for other etiologies of AKI such as sepsis, inflammation and ischemia–reperfusion, have relevance in the treatment of COVID-19 AKI and could be rapidly pivoted to this new disease.

Inhibition of contact-mediated activation of factor XI protects baboons against S aureus–induced organ damage and death

AbstractStaphylococcus aureus infections can produce systemic bacteremia and inflammation in humans, which may progress to severe sepsis or septic shock, even with appropriate antibiotic treatment. Sepsis may be associated with disseminated intravascular coagulation and consumptive coagulopathy. In some types of mouse infection models, the plasma coagulation protein factor XI (FXI) contributes to the pathogenesis of sepsis. We hypothesize that FXI also contributes to the pathogenesis of sepsis in primates, and that pharmacological interference with FXI will alter the outcome of Staphylococcus aureus–induced lethality in a baboon model. Pretreatment of baboons with the anti-FXI antibody 3G3, a humanized variant of the murine monoclonal 14E11 that blocks FXI activation by FXIIa, substantially reduced the activation of coagulation, as reflected by clotting times and plasma complexes of coagulation proteases (FXIIa, FXIa, FIXa, FXa, FVIIa, and thrombin) with serpins (antithrombin or C1 inhibitor) following infusion of heat-inactivated S aureus. 3G3 treatment reduced fibrinogen and platelet consumption, fibrin deposition in tissues, neutrophil activation and accumulation in tissues, cytokine production, kininogen cleavage, cell death, and complement activation. Overall, 3G3 infusion protected the structure and function of multiple vital organs, including lung, heart, liver, and kidney. All treated animals reached the end point survival (7 days), whereas all nontreated animals developed terminal organ failure within 28 hours. We conclude that FXI plays a role in the pathogenesis of S aureus–induced disseminated intravascular coagulation and lethality in baboons. The results provide proof of concept for future therapeutic interventions that may prevent sepsis-induced organ failure and save lives in certain forms of sepsis.

AB001. Sepsis and the heart: an echocardiographic perspective

: Sepsis remains a huge medical challenge with many complexities being unraveled slowly. Worldwide, sepsis represents one of the leading causes death and especially in the developing and underdeveloped countries. In the intensive care units, it is not only a medical challenge, it adds to the cost of healthcare delivery considerably. Cardiac and circulatory consequences of sepsis are well known and need to be addressed as a priority in the critically ill patients. Echocardiography is a great tool to assist in every stage of sepsis management. Septic cardiomyopathy is a well-known entity and may constitute a heart that is hyper dynamic or hypokinetic, often related to fluid resuscitation status. In addition to left and/or right ventricular systolic dysfunction, frequently there is accompanying diastolic dysfunction that may also exist in isolation in sepsis. Patterns of cardiac response are emerging and need to be recognized in both systolic and diastolic function. These patterns of dysfunction may also predict the outcome. Different forms of sepsis might exhibit different cardiac pathology, and will be a good research subject for future. In the management of sepsis proper fluid resuscitation plays a critical role and echocardiography has much to contribute towards a better outcome in these patients.

AB001. Sepsis and the heart: an echocardiographic perspective

: Sepsis remains a huge medical challenge with many complexities being unraveled slowly. Worldwide, sepsis represents one of the leading causes death and especially in the developing and underdeveloped countries. In the intensive care units, it is not only a medical challenge, it adds to the cost of healthcare delivery considerably. Cardiac and circulatory consequences of sepsis are well known and need to be addressed as a priority in the critically ill patients. Echocardiography is a great tool to assist in every stage of sepsis management. Septic cardiomyopathy is a well-known entity and may constitute a heart that is hyper dynamic or hypokinetic, often related to fluid resuscitation status. In addition to left and/or right ventricular systolic dysfunction, frequently there is accompanying diastolic dysfunction that may also exist in isolation in sepsis. Patterns of cardiac response are emerging and need to be recognized in both systolic and diastolic function. These patterns of dysfunction may also predict the outcome. Different forms of sepsis might exhibit different cardiac pathology, and will be a good research subject for future. In the management of sepsis proper fluid resuscitation plays a critical role and echocardiography has much to contribute towards a better outcome in these patients.

Actual problems of the pathology of sepsis: 25 years in search of a consensus

In search of a consensus the authors give current materials on the pathobiology of sepsis, which concerns the definitions, classification, etiology, pathogenesis, and diagnosis of the disease on the basis of their own experience and the data available in the literature. The sepsis problem that is one of the most controversial and complex ones in pathobiology and medical practice has undergone a great very important 25-year stage of development to culminate in the adoption of clinical Sepsis-3 Consensus. International experts have proposed a new definition of sepsis, with an emphasis on the life-threatening condition and the presence of organ dysfunction that can be regarded as an analogous to organ damage. Systemic inflammatory response remains an essential sign of sepsis, but is not strictly specific. Instead of its previous four forms of sepsis, two forms of the disease (sepsis proper and septic shock) have been identified. The Consensus-proposed Sepsis-3 criteria for diagnosing sepsis continue to remain predominantly clinical laboratory ones, confirming the need for further clinicopathological and experimental morphological comparisons in order to achieve a complete understanding of the problem of sepsis between clinicians and pathologists.

Features of cytokine profile in patients with local and generalized soft tissue infections

Aim. To determine the features of cytokine profile in patients with local and generalized soft tissue infections. Methods. The treatment results of 2350 patients with soft tissues infections since 1998 to 2012 were analyzed. ELISA test was used to measure tumor necrosis factor alpha and interleukin-1 receptor antagonist levels in 300 randomly picked patients with local (75 patients, comparison group) and generalized (225 patients, main group) forms of soft tissue infections. Results. In patients with generalized infections, tumor necrosis factor alpha level was 1.5 times higher in patients with mild systemic inflammatory response, 3.5 times higher - in patients with moderate and 6.7 times higher in patients with severe systemic inflammatory response compared to healthy controls. Interleukin-1 receptor antagonist levels were also elevated and related to the degree of inflammatory response, thus, it was the highest (2 times higher compared to controls) in patients with moderate systemic inflammatory response, while in patients with mild and severe inflammation it was only 30-40% higher. The significant increase in tumor necrosis factor alpha level associated with normal interleukin-1 receptor antagonist level is characteristic for different forms of sepsis. At the same time, increase in interleukin-1 receptor antagonist level associated with minimal changes in tumor necrosis factor alpha level can be used as a diagnostic criteria for compensated inflammatory response I patients with local infections cytokine profile was normal. The severity of systemic inflammation and clinical course of generalized infection depended not only on the absolute increase of cytokine levels, but on pro-inflammatory (tumor necrosis factor alpha) and anti-inflammatory (interleukin-1 receptor antagonist) cytokine levels misbalance. Conclusion. Examining the serum cytokine levels allows to confirm the diagnosis of generalized infection on early stages and to differentiate between compensated and non-ompensated systemic inflammatory response.

An Alarm System for Death Prediction

The clinical treatment of sepsis is one of most severe issues in hospitals. Unfortunately, until now it has not been possible to significantly reduce the mortality rate of severe forms of sepsis like septic shock, which is as high as 50-60% worldwide. Often, the diagnosis and awareness for possible implications of sepsis can be facilitated by an automated online diagnosis. This contribution reports the development of a monitoring alarm system for the individual prediction of death based on the data of 382 patients with septic shock. The paper discusses the pros and cons of such a prediction system used in a medical environment, its principal usage issues and implementation.

An analysis of successful litigation claims in childhood Fatalities in England

<h3>Aims</h3> A recent publication analysed successful litigation claims involving children handled by the NHS Litigation Authority (NHSLA). In this study, NHSLA claims in the last 6 years involving a childhood death were investigated. Our aim was to learn from these errors to improve patient safety. <h3>Methods</h3> A Freedom of Information request was made to the NHSLA to obtain a record of claims involving fatalities in children from 1st April 2004 to 31st March 2010. The closed cases where compensation had been paid to the claimant were analysed to explore the causes and diseases that led to a fatality and the costs of litigation. <h3>Results</h3> 130 out of a total of 234 closed cases (56%) resulted in payment of compensation. These cases were analysed. The commonest causes of a fatality were delayed / failed diagnosis (58), delayed/failed treatment (19), complications related to operations/procedures (17), poor overall quality of care (7), medication errors (6), inappropriate medical advice leading to delayed presentation (6) and communication errors (5). The commonest missed diagnoses were meningitis (10), sepsis - unspecified (8), cardiac defects (7), malignancy (3) and meningococcal septicaemia (3). The total cost of litigation was £8,143,342 with cost per case ranging from £1607 to £790,555 with a mean of £62,641. <h3>Conclusion</h3> A delayed or failed diagnosis was the commonest reason for litigation following a fatality. Meningitis and other forms of sepsis were the most commonly missed conditions. Successful litigation following paediatric deaths has cost the NHS in excess of £8 million since 2004. This data suggests areas where training could be improved. Simulation training is increasingly becoming an integral part of paediatric training, with the aim of improving patient safety, communication and team working. Whilst such training is expensive, if it could reduce errors it may save the NHS from the costs of litigation. The death of a child is a tragedy. When an error has occurred, this causes further suffering to the family and to the healthcare professionals involved. However, by learning from such errors, we can diminish such occurrences in the future.

Evaluation of Serum NT‐pCNP as a Diagnostic and Prognostic Biomarker for Sepsis in Dogs

There is a need for diagnostic biomarkers that can rapidly differentiate dogs with sepsis from dogs with noninfectious forms of systemic inflammatory response syndrome (NSIRS). To compare serum NT-pCNP concentrations among dogs with various forms of sepsis, NSIRS, and healthy controls and to evaluate the use of serum NT-pCNP for the diagnosis of various forms of sepsis in dogs. One hundred and twelve dogs including 63 critically ill dogs (sepsis n = 29; NSIRS n = 34) and 49 healthy control dogs. Prospective clinical investigation. Serum samples were collected for NT-pCNP measurement from dogs with sepsis or NSIRS within 24 hours of intensive care unit admission or at the time of presentation for healthy dogs. Dogs with sepsis were subclassified based on the anatomic region of infection. Serum NT-pCNP concentrations were compared among sepsis, NSIRS and healthy groups as well as among sepsis subgroups. The area under the curve (AUC), sensitivity, and specificity for identifying dogs with sepsis were determined. Using a cut-off value of 10.1 pmol/L, AUC, sensitivity, and specificity of NT-pCNP for differentiating dogs with sepsis from dogs with NSIRS or healthy control dogs were 0.71 (95% CI, 0.58-0.85), 65.5% (45.7-82.1%), and 89.2% (80.4-94.9%), respectively. Serum NT-pCNP had poor sensitivity for peritoneal sources of sepsis; AUC [0.92 (0.81-1.0)], sensitivity [94% (71-100%)], and specificity [89% (80-95%)] improved when these dogs were excluded. Serum NT-pCNP concentration was not associated with survival in the sepsis group. Serum NT-pCNP is a promising diagnostic biomarker for sepsis but is a poor indicator of septic peritonitis.

Toll-Like Receptors in Sepsis: A Tale Still Being Told

Sepsis is a complex clinical situation responsible for thousands of deaths annually in intensive care units around the globe. Despite all our progress in providing medical care to critically ill patients, mortality of severe forms of sepsis did not decrease as expected. Part of this phenomenon is due to our defective understanding about the host immune response to aggression by a microorganism, including the part played by the pattern-recognition receptors (PRRs) in this process. PRRs are part of the innate immunity responsible for detecting non-self antigens and trigger the initial inflammatory response. The best known PRRs are the tol-like receptors (TLRs). In this article, we review some of our knowledge regarding the role of TLRs in sepsis, both in experimental models and in human patients. The improvement in our knowledge about the mediators and signaling pathways that control this immune response is crucial for the development of better markers of disease and new therapeutic targets, leading us to improve the way we treat septic patients.

Adjunctive Therapy in Septic Shock and Severe Sepsis

Despite the use of antimicrobials, mortality rates remain very high in patients with severe forms of sepsis. The role of adjunctive therapies is uncertain. In two recent multicenter, randomized trials, researchers investigated the use of such therapies. Sprung and colleagues compared hydrocortisone with placebo in a multinational, double-blind trial involving 499 adults with septic shock. The primary outcome measure was 28-day mortality among patients who did not have a response …

Community-acquired Pneumonia: New Facets of an Old Disease?Hantavirus Pulmonary Syndrome

It seems that with climatic and geoecologic changes, Hantaviruses have re-emerged as human pathogens related to increases in interaction between humans and rodent reservoirs. Infection with SNV in North America and the Andes virus in South America can produce infection manifest initially as a flu-like illness. In the setting of a history of possible exposure to rodents or their excreta, clinical symptoms and laboratory clues such as thrombocytopenia should raise the suspicion of HPS. Clinical deterioration can be rapid, so patients should be hospitalized and transported to tertiary care centers where mechanical ventilation is available if necessary. Presumptive treatment for other forms of sepsis should be considered before confirmation of diagnosis. Survival seems to be determined in part by viral and host factors. Canadian and South American data suggest that there may be species variations influencing clinical manifestations and course of disease. Because the pathogenesis seems to be based on immunologic injury, future treatments will likely focus on interventions other than antiviral medications. Prevention strategies should be emphasized, particularly when recognized climatic conditions favor rodent abundance. Physicians should remain alert to the possibility of such a diagnosis when evaluating a patient with CAP and should request appropriate serology while supporting the patient in a closely monitored setting. The declining mortality rates seen over the past decade may be a consequence of improved medical management or better recognition of cases, including those less severe than originally described.

Empiric antimicrobial therapy for severe sepsis in the intensive care unit: In early, hit hard, out early

Summary Sepsis is becoming more common in hospital patients and, despite developments in management, the morbidity and mortality of severe sepsis is still significant. Early, appropriate antimicrobial therapy has a significant positive effect on outcome and should be a priority in the management of these patients. This means treating empirically with broad-spectrum antimicrobials until the pathogen is identified. Balancing this is the need to avoid increasing antimicrobial resistance which has been shown to be proportional to antimicrobial use. While every effort should be made not to fail individual patients by inadequately treating their sepsis, it is important to minimize resistance by avoiding unnecessary and excessive antimicrobial use. Traditionally, empiric treatment has involved starting with a narrow antimicrobial spectrum and escalating it as culture results become known. Current opinion, however, is veering towards initiating empiric therapy as soon as possible with broad-spectrum antimicrobials, narrowing the spectrum once the organism is identified (de-escalation), and limiting duration of therapy to the minimum effective period. This approach improves outcome and controls antimicrobial resistance. Many of the recommendations on this subject are not supported by high level evidence. Much of the research has been done on hospital and ventilator acquired pneumonia. For the purposes of this paper we are assuming that these findings have relevance to other forms of sepsis. This review of some of the current literature attempts to clarify antimicrobial issues for the Intensive Care SHO or registrar dealing with the onset of severe sepsis in critically ill adults.

Cytokines, chemokines and other effector molecules involved in meningococcal disease.

This review examines the role of cytokines and chemokines in the pathogenesis of meningococcal disease (MCD) and draws comparisons with studies of other forms of sepsis in adults and in animal models. There are many similarities but also discrepancies between these data. MCD is a well-defined clinical syndrome with identifiable onset and time of presentation. It is a reliable model in which to study cytokine and chemokine responses in bacterial sepsis. Such studies may lead to new adjunctive treatments, which can be tested to ameliorate severe MCD.

RENAL FAILURE IN VIBRIO VULNIFICUS INFECTION

Vibrio vulnificus infection with septicemia is a life threatening disease in the immunocompromised hosts. Renal involvement has not been documented. We reported herein 8 patients with V. vulnificus septicemia. All were immunocompromised hosts. Four patients had cirrhosis of the liver, 3 were heavy alcohol drinkers and one had systemic lupus erythematosis. Presenting symptomatology included fever, chills, leg pain and skin rash. Renal failure was observed in 6 patients. Four patients died shortly after admission. Two survived with clinical course of tubular necrosis. Renal failure is therefore common in V. vulnificus infection. This should be brought to attention, and vigorous antibiotic treatment is required. The disease may be confused with leptospirosis, scrub typhus, malaria and other forms of sepsis which also present with renal failure.

T-cryptantigen (TCA) activation in surgical neonates: a hidden problem.

The Thomsen-Friedenreich cryptantigen (TCA) is located on the surface of all red cells, but is concealed by a layer of neuraminic acid. When bacteria that produce neuraminidase disrupt this coating, the TCA can be exposed and activated. If blood products containing antibody to the TCA are subsequently administered, haemolysis can result. While the relationship between TCA and necrotising enterocolitis (NEC) is well described, the incidence of TCA activation in other forms of sepsis in surgical neonates is not known. In a prospective study, 117 patients admitted to the Surgical Neonatal Nursery were examined for evidence of TCA activation. Of the 117 babies, 69 were clinically non-septic and only 1 had weak TCA activation (1.4%). Forty-eight were clinically or bacteriologically septic; 8 of these demonstrated TCA activation (17%), 3 of whom died. Forty of the septic group showed no evidence of TCA activation although 27 grew organisms on culture; 17 in this group died. Two of the TCA-activated babies received unwashed red cells, and both haemolysed; 4 TCA-activated babies received washed red cells and none haemolysed. Although 1 of the well babies in this study demonstrated TCA activation, we would not recommend routine TCA testing on clinically well babies. We would, however, recommend routine testing in all clinically septic infants, as 17% showed signs of TCA activation in this study. We would also suggest the adoption of a selective transfusion policy in TCA-activated patients to avoid the risk of haemolysis. This may help to reduce unnecessary morbidity and mortality in a high-risk group of neonates.