Septic Course Research Articles

Long-term Outcomes and Effectiveness of Treatment Methods for Vertebral Osteomyelitis With Different Types of Lesions According to the E. Pola Classification

Background. Treatment of vertebral osteomyelitis (VO) is accompanied by a number of organizational and tactical problems related to the multidisciplinary nature of the disease. Therefore, the use of classifications determining treatment tactics is necessary. The evaluation of treatment outcomes and efficacy should be conducted in accordance with the classification type of the lesion and decisions made based on the tactical algorithm.
 Aim of the study to identify the dependence of long-tenn treatment outcomes of vertebral osteomyelitis on the type of lesion according to the modified Russian version of the E. Pola classification and the methods of treatment used.
 Methods. The study analyzed the treatment results of 266 patients with vertebral osteomyelitis from 2006 to 2019. Type A lesions accounted for 24.1% (n = 64), type B 47.0% (n = 125), type C 26.3% (n = 70), and lesions of vertebral processes 2.6% (n = 7). Neurological disorders were detected in 53 observations (type C). Conservative treatment, debridement, and reconstructive surgeries were perfonned. The evaluation of results was carried out a year or more after discharge.
 Results. The maximum effectiveness of conservative treatment was noted in uncomplicated courses and minor bone destruction. Conservative treatment of type A lesions led to recovery in 97.4% of cases compared to reconstructive operations (p = 0.002) and recurrences (p = 0.034). Mortality was higher after reconstructive interventions (p = 0.001). The highest number of fatal outcomes after debridement of the focus was observed in type B lesions 15.8% (p = 0.022). Analysis of type C lesions did not reveal significant differences between the methods of treatment used. The maximum number of unsatisfactory results was registered in patients with sepsis: mortality was 17.4%, and in its absence 4.9% (p = 0.039), recurrences 21.7% versus 7.8% (p = 0.043), recovery 56.6% versus 83.5% (p = 0.004), respectively. There were no significant differences in the assessments according to the ODI, NDI, SF-36 scales in the long tenn. The overall survival rate was 84.4%, and the long-tenn one was 90.4%, which increased with conservative treatment compared to reconstructive interventions (p = 0.045).
 Conclusion. Conservative treatment and extra-focal fixation of the spine showed maximum effectiveness in low-destructive and uncomplicated lesions (type A). Reconstructive interventions lead to an increase in the number of recurrences and fatal outcomes. Debridement of the focus in septic course of type В lesions leads to an increase in hospital mortality. There were no statistically significant differences between the results of different treatment methods for type C lesions.

Listeria endocarditis

Bacterial infections caused by Listeria monocytogenes are rarely observed in routine clinical practice. Symptoms can range from comparatively unspecific to severe, septic courses of disease with cardiac, pulmonary, abdominal or bone involvement. A74-year-old male patient with ahistory of mitral valve replacement and pacemaker implantation presented to the emergency department with high fever and disturbed coagulation. Transesophageal echocardiography revealed mitral valve endocarditis with early abscess formation. In blood cultures, growth of Listeria monocytogenes was detected after 20 h. Despite immediately initiated calculated antibiotic therapy and following adaption to the resistogram, the mitral valve finding was progressive and cardiosurgical intervention became necessary. Diagnosis of endocarditis caused by Listeria requires structured collaboration between cardiologists, imaging and laboratory. This case report aims to increase awareness of potentially Listeria-induced organ manifestations.

Prevalence of COVID-19 Among Older People with Type 2 Diabetes Mellitus: A Systematic Review

Background: On March 11, 2020, the WHO proclaimed the Coronavirus Disease 2019 (COVID-19) pandemic owing to coronavirus-2 (SARS-CoV-2). SARS-CoV-2 is a zoonotic virus that may be spread from bats to humans through airborne droplets and aerosols. SARS-CoV-2 spike protein has a high binding affinity for ACE2 receptors, widely expressed throughout the respiratory system, notably in epithelial lung cells. ACE2 receptors are found in intestinal mucosal, endothelial, heart, renal epithelial as well as cerebral neuronal cells, explaining COVID-19 extrapulmonary symptoms like diarrhea, nausea, vomiting, chest pain, heart failure, renal injury, headache, and confusion. Older persons with type2 diabetes mellitus and hypertension are more susceptible to SARS-CoV-2 infection as drugs by which they are treated promote ACE2 receptor expression. Moreover, comorbidities increase the probability of poor outcomes after infection by the SARS-CoV-2. Research links COVID-19 to hyperglycemia in the elderly with type 2 diabetes. Twenty percent of people with diabetes get severe pneumonia and a septic course from viral infections. Diabetes contributed to sickness severity and fatality in MERS (MERS-CoV). Epidemiological findings in SARS-CoV-2-affected regions, CDC data, and other national health centers and hospitals suggest that individuals with diabetes had a 50% greater chance of dying from COVID-19. Methods: This systematic review involves a critical and reproducible summary of the results of the available publications on COVID-19 and diabetic elderly patients’ topics and questions. Fourteen studies (6 retrospective cohorts, two prospective, two cohorts, one combined retrospective, one observational, one cross-sectional, and one hospital-based study) were included in this systematic review. Results: From all studies, the mean age of older adults with type 2 diabetes mellitus who suffered from COVID-19 was 50 to 89 years. The majority of the studies showed the male predominance of infection. The pooled prevalence of COVID-19 among diabetes mellitus elderly patients was 29.8%. Conclusions: Diabetes patients had a greater COVID-19 prevalence and severity, according to several explanations. Diabetes Mellitus increases the risk of infection due to innate and adaptive immunity deficiencies. Post COVID-19 complications arise due to a lack of equilibrium between pro-inflammatory and anti-inflammatory cytokine networks in type 2 diabetes mellitus, contributing to increased mortality. Therefore, this study necessitates a large investigational study to find out how to boost the immune response against SARS-CoV-2 infection in an equilibrium manner not to produce much inflammatory cytokine in type 2 diabetes mellitus individuals to reduce the risk of developing complications and mortality consequently. Keywords: COVID-19, Diabetes mellitus, Type-2 diabetes, Elderly.

Treatment of Acute Lung Abscesses Considering their Non-Respiratory Function in Patients with Diabetes

During the examination and treatment of 465 patients with acute lung abscesses on the background ofdiabetes mellitus, a preoperative preparation program was developed that takes into account the phase of theprocess (group 1 - septic course of the process, group 2 - stabilization, group 3 - remission), the severity ofendotoxemia and non-respiratory lung function. Patients of the 1st group against the background of basiclong-term intra-arterial catheter therapy used the scheme of correction of non-respiratory function of thelungs that we developed, sanitized purulent foci with an electrolyzed solution of sodium hypochlorite. In202 (79.9%) of 254 patients of the 1st group, it was effective that allowed to refuse the operation, while only52 (40.6%) were not operated on in the 2nd, and 26 in the 3rd (31.3%) patients. In parallel, a pronouncednormalizing effect was achieved in correcting the degree of violation of non-respiratory lung functionagainst the background of delimitation and stabilization of the process. This allowed in 109 (60.9%) of 179operated patients to confine themselves to lung resection with 8.7% of postoperative complications in the 1stgroup versus 18.4% in the 2nd and 24.6% in the 3rd, which emphasizes the effectiveness of our preoperativepreparation.

COVID-19 Pandemic as an Indicator of «Blank Spots» in Epidemiology and Infectious Pathology

The COVID-19 (Coronavirus Disease 2019) pandemic revealed many «blank spots» in epidemiology at that very moment when humanity became confident that all epidemic disasters had remained in the distant past. The aim of this article is to study COVID-19 pandemic as an indicator of «blank spots» in epidemiology and infectious pathology. The article substantiates that the COVID-19 epidemic started much earlier than it was identified and recognized in China. The failure to establish the primary natural reservoir of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) among vertebrates suggests an expansion of searches for invertebrates. The reasons for the global spread of SARS-CoV-2 may be the presence of numerous unidentified primary and secondary natural foci of the virus among animals living close to humans, the high transmissibility of the virus and its presymptomatic transmission. High transmissibility of SARS-CoV-2 is possible because: the binding energy of S1 protein of the virus with its receptor ACE2 is higher than that of viruses of closely related species; the virus penetrates into the endosomes of the cells more efficiently; because of the work of the replication-transcription complex, which counteracts the innate protective response of cells. The presymptomatic transmission of SARS-CoV-2, which has become the main reason for the pandemic spread of SARS-CoV-2, is a consequence of the late detection of the virus by the innate immune system. Infected individual becomes contagious first, and then the specific symptomThe COVID-19 (Coronavirus Disease 2019) pandemic revealed many «blank spots» in epidemiology at that very moment when humanity became confident that all epidemic disasters had remained in the distant past. The aim of this article is to study COVID-19 pandemic as an indicator of «blank spots» in epidemiology and infectious pathology. The article substantiates that the COVID-19 epidemic started much earlier than it was identified and recognized in China. The failure to establish the primary natural reservoir of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) among vertebrates suggests an expansion of searches for invertebrates. The reasons for the global spread of SARS-CoV-2 may be the presence of numerous unidentified primary and secondary natural foci of the virus among animals living close to humans, the high transmissibility of the virus and its presymptomatic transmission. High transmissibility of SARS-CoV-2 is possible because: the binding energy of S1 protein of the virus with its receptor ACE2 is higher than that of viruses of closely related species; the virus penetrates into the endosomes of the cells more efficiently; because of the work of the replication-transcription complex, which counteracts the innate protective response of cells. The presymptomatic transmission of SARS-CoV-2, which has become the main reason for the pandemic spread of SARS-CoV-2, is a consequence of the late detection of the virus by the innate immune system. Infected individual becomes contagious first, and then the specific symptoms of the disease appear. It is suggested in the article, that the COVID-19 pandemic is not an independent event caused by the emergence of a «new virus» (like one more flu pandemic), but a manifestation of a more complex and dangerous phenomenon, i.e. a change of the phase of the centuries-old global pandemic cycle, when, due to the increase in the density of immunodeficient populations weakened by various pathologies (chronic diseases, accumulation of genetic defects, aging, etc.) and aggravated social problems, non-cyclic pandemics and cyclical low-contagious epidemics are replaced by cyclical ones caused by highly contagious pathogens. SARS-CoV-2 is not the last in these events. The severe clinical course of COVID-19 is caused by such poorly understood phenomena as «imbalance» of renin–angiotensin–aldosterone system, cytokine storm, septic course of the disease, the patient`s genetic factors and immunopathology, developed during the infectious process (antibody-dependent enhancement enhancement of infection, antigenic imprinting, antiphospholipid syndrome and other factors). Filling these «blank spots» will catalyze a research revolution in epidemiology and infectious pathologys of the disease appear. It is suggested in the article, that the COVID-19 pandemic is not an independent event caused by the emergence of a «new virus» (like one more flu pandemic), but a manifestation of a more complex and dangerous phenomenon, i.e. a change of the phase of the centuries-old global pandemic cycle, when, due to the increase in the density of immunodeficient populations weakened by various pathologies (chronic diseases, accumulation of genetic defects, aging, etc.) and aggravated social problems, non-cyclic pandemics and cyclical low-contagious epidemics are replaced by cyclical ones caused by highly contagious pathogens. SARS-CoV-2 is not the last in these events. The severe clinical course of COVID-19 is caused by such poorly understood phenomena as «imbalance» of renin–angiotensin–aldosterone system, cytokine storm, septic course of the disease, the patient`s genetic factors and immunopathology, developed during the infectious process (antibody-dependent enhancement enhancement of infection, antigenic imprinting, antiphospholipid syndrome and other factors). Filling these «blank spots» will catalyze a research revolution in epidemiology and infectious pathology

Spondylodiscitis

Spondylodiscitis is an infection of the spine that first affects the vertebral endplates ("spondylitis") and then spreads to the adjacent intervertebral disc ("spondylodiscitis"). As it is a potentially life-threatening systemic disease rapid, often surgical treatment is required. Due to the multimorbidity of the patients and the complexity of the therapy, a multidisciplinary approach is essential. The vast majority of the cases heals under conservative therapy. An absolute indication for surgical therapy is given for acute septic courses or if there are new relevant neurological deficits. In addition, urgent surgical treatment is required for epidural abscesses that can be diagnosed by means of magnetic resonance imaging. In developed countries, over 90% of all spondylodiscitis cases come to a complete recovery.

Abrupt Discontinuation Versus Down-Titration of Vasopressin in Patients Recovering from Septic Shock

To compare patient outcomes based on management of arginine vasopressin (AVP) during the recovery phase of septic shock (abrupt vs. tapering discontinuation). Multicenter, retrospective cohort study of patients receiving AVP with concomitant norepinephrine for septic shock. Primary outcome measure was time to intensive care unit (ICU) discharge (from decision to titrate or stop AVP). Secondary outcomes included ICU and hospital mortality, and incidence of hypotension. A total of 958 (73%) abrupt discontinuation and 360 (27%) down-titration patients were included. Patient characteristics and septic shock treatment courses were similar between groups. Median time to ICU discharge was similar between abrupt discontinuation (7.9 days, 95% CI 7.2-8.7 days) and tapered patients (7.3 days, 95% CI 6.3-9.3 days, P = 0.60). After controlling for baseline discrepancies, down-titration was not an independent predictor of time to ICU discharge (HR = 0.99, 95% CI: 0.85-1.15, P = 0.91). There was no difference in ICU mortality (21.8% vs. 18.0%, P = 0.13) or hospital mortality (28.9% vs. 31.1%, P = 0.44). Although incidence of hypotension was similar (39.7% vs. 41.7%, P = 0.53), patients in the down-titration group more frequently required an escalation of AVP dose (5.7% vs. 11.1%, P < 0.001). Median AVP duration was shorter in the abrupt discontinuation group (1.4 days [IQR: 0.6-2.6 days] vs. 1.8 days [IQR: 1.1-3.2 days], P < 0.001). A difference in time to ICU discharge was not detected between abrupt AVP discontinuation and down-titration in patients recovering from septic shock. In patients recovering from septic shock, abrupt discontinuation of AVP appears to be safe and may lead to shortened AVP duration.

Cell Cycle Biomarkers and Soluble Urokinase-Type Plasminogen Activator Receptor for the Prediction of Sepsis-Induced Acute Kidney Injury Requiring Renal Replacement Therapy: A Prospective, Exploratory Study

Sepsis-induced acute kidney injury is the dominant acute kidney injury etiology in critically ill patients and is often associated with a need for renal replacement therapy. The indication and timing of renal replacement therapy are controversially discussed. We hypothesized that the product of the G1-cell cycle arrest biomarkers tissue inhibitor of metalloproteinase-2 and insulin-like growth factor-binding protein 7 ([TIMP-2] × [IGFBP7]), and the soluble urokinase-type plasminogen activator receptor are of diagnostic value for the prediction of septic acute kidney injury courses requiring renal replacement therapy. In this prospective study, critically ill patients were enrolled immediately after the fulfillment of Sepsis-3 criteria. Urinary [TIMP-2] × [IGFBP7] levels over time and serum soluble urokinase-type plasminogen activator receptor levels once at inclusion were measured. The primary endpoint was the development of septic acute kidney injury with the need for renal replacement therapy. Area under the receiver operating characteristic curves, de Long's tests, and logistic regression models were calculated. Two ICUs at Heidelberg University Hospital between May 2017 and July 2018. One-hundred critically ill patients with positive Sepsis-3 criteria. None. Nineteen patients required renal replacement therapy. Diagnostic performance of urinary [TIMP-2] × [IGFBP7] improved over time with the highest area under the receiver operating characteristic curve of 0.89 (95% CI, 0.80-0.98) 24 hours after study inclusion. Soluble urokinase-type plasminogen activator receptor levels at inclusion showed an area under the receiver operating characteristic curve of 0.83 (0.75-0.92). The best discrimination ability for the primary outcome measure was achieved for [TIMP-2] × [IGFBP7] at 24 hours after inclusion by applying a cutoff value of greater than or equal to 0.6 (ng/mL)/1,000 (sensitivity 90.9, specificity 67.1). Soluble urokinase-type plasminogen activator receptor performed best by using a cutoff value of greater than or equal to 8.53 ng/mL (sensitivity 84.2, specificity 82.7). A combination of newly tested biomarkers with cystatin C resulted in a significantly improved diagnostic accuracy. Cystatin C in combination with [TIMP-2] × [IGFBP7] 24 hours outperformed all standard renal parameters (area under the receiver operating characteristic curve 0.93 [0.86-1.00]). [TIMP-2] × [IGFBP7] and soluble urokinase-type plasminogen activator receptor are promising biomarker candidates for the risk stratification of septic acute kidney injury patients with the need for renal replacement therapy.

Dynamic changes in human HLA-DRA gene expression and Th cell subsets in sepsis: Indications of immunosuppression and associated outcomes.

Sepsis is a life-threatening disease that is an immune disorder response that causes multiple organ dysfunction. In this study, we investigated the dynamic changes in mRNA expression of HLA-DRA gene and the specific transcription factor of helper T cell subsets to explore long-term immunophenotyping and its relationship with prognosis. Seventy-eight sepsis patients and twelve healthy controls were recruited in this study. Blood samples were collected at eight-time points during their septic course and were assayed for the gene expression of HLA-DRA and T helper cell subset-specific transcription factors (T-bet: Th1, GATA3: Th2, Foxp3: Treg, RORC: Th17). The levels of HLA-DRA in survivors gradually increased but were maintained at lower levels in non-survivors. The specific transcription factor of Th1 and Th2 cells, T-bet and GATA-3 were significantly lower in sepsis patients than in normal controls, and the non-survivors showed significantly lower levels than the survivors (P<.05). RORC and FOXP3, the specific transcription factor of Treg and Th17 were significantly higher in survivors than in non-survivors and normal controls (P<.05). T-bet and GATA-3 had a linear correlation with HLA-DRA expression (P<.01). The dynamic changes in HLA-DRA expression in peripheral blood could accurately reflect the immune status of sepsis patients, and the reduction in HLA-DRA may be an important reason for abnormal T cell differentiation. The sustained low levels of the Th cell subsets (Th1 and Th2) suggest the suppression of adaptive immunity, and this persistent immunosuppression may be the leading cause of death in septic patients.

Sepsis 2019 - New Trends and Their Implications for Multiple Trauma Patients.

In spring 2016, an updated sepsis definition (Sepsis-3) introduced a new explanation for the clinical picture of sepsis. Until then, sepsis had been understood as a "systemic inflammatory response syndrome (SIRS)" resulting from infection. An improved understanding of the molecular mechanisms and broad epidemiological studies of the clinical appearance shifted the focus from the inflammatory response to the multicausal tissue damage resulting in organ dysfunction. This paradigm shift highlights organ failure as a result of a dysregulated response of an organism to infection. Central to the new definition is the understanding that sepsis patients form a heterogeneous group and that the clinical picture requires alternative explanation patterns: e.g. sepsis is insufficiently explained by an overwhelming inflammatory response, it also comprises "immune paralysis" as another important pattern. Furthermore, severity of sepsis reflects the capacity of an organism to adapt and to mitigate the tissue damage through metabolic changes and repair mechanisms. Consistent with the paradigm of the new sepsis definition, adaptation in the presence of infections is crucial for the organism. Seriously injured or multiple trauma patients represent a patient group at particular risk, as sepsis often complicates the courses of these patients due to nosocomial infections. Along with comorbidities, past infections and age, leakage of skin and intestinal barriers as well as impaired defence and repair mechanism predispose trauma patients for a septic course. New pathophysiological insights suggest that the control of extracellular haem is of paramount significance. Haemolysis, transfusion and the consecutive expression of haem binding (such as haemopexin) or haem catabolic pathways (such as haem oxygenase) impair the ability of an organism to adapt, correlate with the prognosis and/or are strongly influenced by the surgical treatment concepts. Established treatment concepts of early causal and supportive therapy (damage control, antibiotic and fluid therapy) contribute to the reduction of mortality, depending on stringent implementation as part of Standard Operating Procedures (SOPs) and quality management. The paradigm shift in sepsis research offers an improved understanding of the underlying pathogenic factors within complex and heterogeneous patient groups, such as nosocomial sepsis following trauma. These novel approaches will allow developing new treatment strategies potentially contributing to a significant reduction in morbidity and mortality of trauma patients.Key messages1) According to the new paradigm, the ability to adapt to the pathogenic load associated with trauma and infection is crucial for an organism.2) Seriously injured or multiple trauma patients are predisposed for septic courses due to impaired adaptation mechanisms.3) Established treatment concepts of early causal and supportive therapy (damage control, antibiotic treatment, restrictive transfusion, and volume resuscitation) reduce mortality, in particular as part of SOPs and quality management strategies.4) Newly emerging treatment concepts that focus on the control of extracellular haem are promising, but require more evidence for translation into clinical practice.

Review of the evidence for the use of biomarkers in the diagnosis of sepsis

Major trauma still represents one of the leading causes of death in the first four decades of life. Septic complications represent the predominant causes of late death (45% of overall mortality) in polytrauma patients. The ability of clinicians to early differentiate between systemic inflammatory response syndrome (SIRS) and sepsis is demonstrated to improve clinical outcome and mortality. The identification of an “ideal” biomarker able to early recognize incoming septic complications in trauma patients is still a challenge for researchers.To evaluate the existing evidence regarding the role of biomarkers to predict or facilitate early diagnosis of sepsis in trauma patients, trying to compile some recommendations for the clinical setting.An Internet-based search of the MEDLINE, EMBASE and Cochrane Library databases was performed using the search terms: “Biomarkers”, “Sepsis” and “Trauma” in various combinations. The methodological quality of the included studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies Checklist (QUADAS). After data extraction, the level of evidence available for each bio-marker was rated and presented using the “best-evidence synthesis” method, in line with the US Agency for Healthcare Research and Quality.Thirty studies were eligible for the final analysis: 13 case–control studies and 17 cohort studies. The “strong evidence” available demonstrated the potential use of procalcitonin as an early indicator of post-traumatic septic complications and reported the inability of c-reactive protein (CRP) to specifically identify infective complications. Moderate, conflicting and limited evidence are available for the other 31 biomarkers.Several biomarkers have been evaluated for predicting or making early diagnosis of sepsis in trauma patients. Current evidence does not support the use of a single biomarker in diagnosing sepsis. However, procalcitonin trend was found to be useful in early identification of post-traumatic septic course and its use is suggested (Recommendation Grade: B) in clinical practice.

Bacterial sepsis : Diagnostics and calculated antibiotic therapy.

The mortality of patients with sepsis and septic shock is still unacceptably high. An effective calculated antibiotic treatment within 1h of recognition of sepsis is an important target of sepsis treatment. Delays lead to an increase in mortality; therefore, structured treatment concepts form a rational foundation, taking relevant diagnostic and treatment steps into consideration. In addition to the assumed infection and individual risks of each patient, local resistance patterns and specific problem pathogens must be taken into account during the selection of anti-infective treatment. Many pathophysiologic alterations influence the pharmacokinetics (PK) of antibiotics during sepsis. The principle of standard dosing should be abandoned and replaced by an individual treatment approach with stronger weighting of the pharmacokinetics/pharmacodynamics (PK/PD) index of the substance groups. Although this is not yet the clinical standard, prolonged (or continuous) infusion of β‑lactam antibiotics and therapeutic drug monitoring (TDM) can help to achieve defined PK targets. Prolonged infusion is sufficient without TDM, but for continuous infusion, TDM is generally necessary. Afurther argument for individual PK/PD-oriented antibiotic approaches is the increasing number of infections due to multidrug-resistant (MDR) pathogens in the intensive care unit. For effective treatment, antibiotic stewardship teams (ABS teams) are becoming more established. Interdisciplinary cooperation of the ABS team with infectious disease (ID) specialists, microbiologists, and clinical pharmacists leads not only to rational administration of antibiotics, but also has a positive influence on treatment outcome. The gold standards for pathogen identification are still culture-based detection and microbiologic resistance testing for the various antibiotic groups. Despite the rapid investigation time, novel polymerase chain reaction(PCR)-based procedures for pathogen identification and resistance determination are currently only an adjunct to routine sepsis diagnostics, due to the limited number of studies, high costs, and limited availability. In complicated septic courses with multiple anti-infective therapies or recurrent sepsis, PCR-based procedures can be used in addition to treatment monitoring and diagnostics. Novel antibiotics represent potent alternatives in the treatment of MDR infections. Due to the often defined spectrum of pathogens and the practically (still) absent resistance, they are suitable for targeted treatment of severe MDR infections (therapy escalation). (Contribution available free of charge by "Free Access" [ https://link.springer.com/article/10.1007/s00101-017-0396-z ].).

Clostridium difficile Infection: Epidemiology, Clinical Presentation, Therapy and Prevention

Clostridium difficile infections (CDI) are common causes of diarrhoea in hospitalised medical and surgical patients. Clinical presentation ranges from mild diarrhoea to pseudomembraneous enterocolitis of the colon and sometimes the small intestines, with development of a toxic megacolon. Recurrent infections are common. Early diagnosis is necessary because of high rates of complications and mortality. Knowledge of risk factors for the development of CDI is recommended. Early initiation of therapy is recommended to avoid complications and standard therapy is antibiotics, while therapy with monoclonal antibodies and vaccination is under research and development. Fulminant septic courses indicate surgical source control. Minimally invasive surgical therapy establishing a loop ileostomy and antibiotic installation via enema has to be considered as early surgical intervention. Fecal microbiotic transplantation is a new therapeutic option for recurrent infection. Provisions for prevention and control have to be established to avoid in-hospital spread of pathogenic agents. This includes isolation of patients, personalisation of instruments, restriction of in-hospital transports, protective clothing and gloves, strict hand washing and antibiotic stewardship (ABS).

Bacterial sepsis : Diagnostics and calculated antibiotic therapy

The mortality of patients with sepsis and septic shock is still unacceptably high. An effective antibiotic treatment within 1 h of recognition of sepsis is an important target of sepsis treatment. Delays lead to an increase in mortality; therefore, structured treatment concepts form a rational foundation, taking relevant diagnostic and treatment steps into consideration. In addition to the assumed focus and individual risks of each patient, local resistance patterns and specific problem pathogens must be taken into account for selection of anti-infection treatment. Many pathophysiological alterations influence the pharmacokinetics of antibiotics during sepsis. The principle of standard dosing should be abandoned and replaced by an individual treatment approach with stronger weighting of the pharmacokinetics/pharmacodynamics (PK/PD) index of the substance groups. Although this is not yet the clinical standard, prolonged (or continuous) infusion of beta-lactam antibiotics and therapeutic drug monitoring (TDM) can help to achieve defined PK targets. Prolonged infusion is sufficient without TDM but for continuous infusion TDM is basically necessary. Afurther argument for individual PK/PD-oriented antibiotic approaches is the increasing number of infections due to multidrug resistant pathogens (MDR) in the intensive care unit. For effective treatment antibiotic stewardship teams (ABS team) are becoming more established. Interdisciplinary cooperation of the ABS team with infectiologists, microbiologists and clinical pharmacists leads not only to a rational administration of antibiotics but also has a positive influence on the outcome. The gold standards for pathogen detection are still culture-based detection and microbiological resistance testing for the various antibiotic groups. Despite the rapid investigation time, novel polymerase chain reaction (PCR)-based procedures for pathogen identification and resistance determination, are currently only an adjunct to routine sepsis diagnostics due to the limited number of studies, high costs and limited availability. In complicated septic courses with multiple anti-infective treatment or recurrent sepsis, PCR-based procedures can be used in addition to therapy monitoring and diagnostics. Novel antibiotics represent potent alternatives in the treatment of MDR infections. Due to the often defined spectrum of pathogens and the practically absent resistance, they are suitable for targeted treatment of severe MDR infections (therapy escalation).

Risk factors and features of septic course in infants

Risk factors and features of septic course in infants

Pre-emptive endoscopic vacuum therapy for treatment of anastomotic ischemia after esophageal resections.

Background and study aims Endoscopic vacuum therapy (EVT) is a promising new approach for the treatment of anastomotic leakage in the gastrointestinal tract. Here, we present the first case series demonstrating successful use of EVT for the treatment of post-esophagectomy anastomotic ischemia prior to development of leakage. Patients and methods Between 2012 and 2015, intraluminal EVT was performed in eight patients with anastomotic ischemia following esophagectomy. The primary outcome measure was successful mucosal recovery. Secondary outcome measures were duration of treatment, number of sponge changes, septic course, and associated complications. Results Complete mucosal recovery was achieved in six patients (75 %) with different degrees of anastomotic ischemia. In two patients (25 %), small anastomotic leaks developed, which resolved by continuing the EVT treatment. Median duration of EVT treatment until mucosal recovery was 16 days (range 6 - 35), with a median of 5 sponge changes per patient (range 2 - 11). No EVT-associated complications were noted. Three patients developed anastomotic stenoses, which were treated by endoscopic dilation therapy. Conclusion This is the first case series to demonstrate that the early use of EVT potentially modulates clinical outcomes and infection parameters in patients with anastomotic ischemia following esophagectomy. Further studies are needed to define the indications and patients who are most likely to benefit from early EVT.

In neonates S100A8/S100A9 alarmins prevent the expansion of a specific inflammatory monocyte population promoting septic shock.

The high susceptibility of newborn infants to sepsis is ascribed to an immaturity of the neonatal immune system, but the molecular mechanisms remain unclear. Newborn monocytes massively release the alarmins S100A8/S100A9. In adults, these are major regulators of immunosuppressive myeloid-derived suppressor cells (MDSCs). We investigated whether S100A8/S100A9 cause an expansion of monocytic MDSCs (Mo-MDSCs) in neonates, thereby contributing to an immunocompromised state. Mo-MDSCs have been assigned to CD14+/human leukocyte antigen (HLA)-DR-/low/CD33+ monocytes in humans and to CD11b+/Gr-1int/Ly6G-/Ly6Chi cells in mice. We found monocytes with these phenotypes significantly expanded in their respective newborns. Functionally, however, they did not prove immunosuppressive but rather responded inflammatorily to microbial stimulation. Their expansion did not correlate with high S100A8/S100A9 levels in cord blood. Murine studies revealed an excessive expansion of CD11b+/Gr-1int/Ly6G-/Ly6Chi monocytes in S100A9-/- neonates compared to wild-type neonates. This strong baseline expansion was associated with hyperinflammatory responses during endotoxemia and fatal septic courses. Treating S100A9-/- neonates directly after birth with S100A8/S100A9 alarmins prevented excessive expansion of this inflammatory monocyte population and death from septic shock. Our data suggest that a specific population of inflammatory monocytes promotes fatal courses of sepsis in neonates if its expansion is not regulated by S100A8/S100A9 alarmins.-Heinemann, A. S., Pirr, S., Fehlhaber, B., Mellinger, L., Burgmann, J., Busse, M., Ginzel, M., Friesenhagen, J., von Köckritz-Blickwede, M., Ulas, T., von Kaisenberg, C. S., Roth, J., Vogl, T., Viemann, D. In neonates S100A8/S100A9 alarmins prevent the expansion of a specific inflammatory monocyte population promoting septic shock.

Comparison of monocyte human leukocyte antigen-DR expression and stimulated tumor necrosis factor alpha production as outcome predictors in severe sepsis: a prospective observational study.

BackgroundIdentifying patients in the immunosuppressive phase of sepsis is essential for development of immunomodulatory therapies. Little data exists comparing the ability of the two most well-studied markers of sepsis-induced immunosuppression, human leukocyte antigen (HLA)-DR expression and lipopolysaccharide (LPS)-induced tumor necrosis factor alpha (TNF-ɑ) production, to predict mortality and morbidity. The purpose of this study was to compare HLA-DR expression and LPS-induced TNF-ɑ production as predictors of 28-day mortality and acquisition of secondary infections in adult septic patients.MethodsA single-center, prospective observational study of 83 adult septic patients admitted to a medical or surgical intensive care unit. Blood samples were collected at three time points during the septic course (days 1–2, days 3–4, and days 6–8 after sepsis diagnosis) and assayed for HLA-DR expression and LPS-induced TNF-ɑ production. A repeated measures mixed model analysis was used to compare values of these immunological markers among survivors and non-survivors and among those who did and did not develop a secondary infection.ResultsTwenty-five patients (30.1 %) died within 28 days of sepsis diagnosis. HLA-DR expression was significantly lower in non-survivors as compared to survivors on days 3–4 (p = 0.04) and days 6–8 (p = 0.002). The change in HLA-DR from days 1–2 to days 6–8 was also lower in non-survivors (p = 0.04). Median HLA-DR expression decreased from days 1–2 to days 3–4 in patients who developed secondary infections while it increased in those without secondary infections (p = 0.054). TNF-ɑ production did not differ between survivors and non-survivors or between patients who did and did not develop a secondary infection.ConclusionsMonocyte HLA-DR expression may be a more accurate predictor of mortality and acquisition of secondary infections than LPS-stimulated TNF-ɑ production in adult medical and surgical critically ill patients.Electronic supplementary materialThe online version of this article (doi:10.1186/s13054-016-1505-0) contains supplementary material, which is available to authorized users.

Fournier’s gangrene

The review highlights the issues of etiology, pathogenesis, clinical and laboratory picture, radiodiagnosis, treatment and prognosis of fulminant perineum gangrene, or Fournier’s gangrene. According to modern concepts, Fournier’s gangrene is one of the rare forms of necrotizing fasciitis of polymicrobial etiology with a primary lesion of the skin, subcutaneous tissue and superficial fascia of the scrotum, penis, and perineum. Fournier’s gangrene refers to acute surgical diseases of pyonecrotic nature and is characterized by rapid septic course, high mortality, reaching 80%, in spite of the modern antibiotic therapy advances. Over the last decade the Fournier’s gangrene incidence increased in 2.2-6.4 times, due to the increasing number of immunocompromised patients in the population. The disease most often occurs in older men with diabetes, alcoholism and obesity. The Fournier’s gangrene occurrence is preceded by different inflammatory diseases of the colon, urinary organs, scrotum and perineum skin. The disease diagnosis in full-scale stage usually is not difficult. In rare cases, namely in the disease early stages, various radiological methods of investigation, laboratory tests and exploratory surgery with affected soft tissues express biopsy are used with differential diagnosis purposes. The cornerstone in the Fournier’s gangrene treatment is an emergency surgical intervention in combination with a powerful anti-bacterial and anti-shock therapy. To improve the wound healing course and reduce the septic complications risk, new methods of adjuvant treatments such as hyperbaric oxygen therapy and vacuum therapy are used. Hospitalization duration in Fournier’s gangrene is usually lengthy, due to the need to use repeated sanitation necrectomy and reconstructive plastic surgery and are associated with considerable economic costs for treatment. The Fournier’s gangrene prognosis depends on the timing of specialized medical care provision and, above all, on the time interval between the disease onset and surgery performing.

Management of Tracheo- or Bronchoesophageal Fistula After Ivor-Lewis Esophagectomy.

The development of tracheo- or bronchoesophageal fistula (TBF) after Ivor-Lewis esophagectomy remains to be a rare complication associated with a high mortality rate. In this retrospective study, the charts of patients with TBF after esophagectomy were analyzed in terms of individual patient characteristics, esophagotracheal complications, respiratory function, management, and outcome. Between January 2000 and December 2014, 1204 patients underwent Ivor-Lewis esophagectomy for esophageal cancer; 13 patients (1.1%) developed a TBF. In all 13 patients, a concomitant leakage of the intrathoracic esophagogastrostomy was evident, either prior to diagnosis of TBF (metachronous TBF) or simultaneously (synchronous TBF). TBF was predominantly located in the left main bronchus (n=6, 46.1%) or trachea (n=5, 38.5%). Management of TBF included re-thoracotomy (n=7), interventional endoscopic (n=10) or bronchoscopic therapy (n=4). In the majority of patients (n=8), management consisted of two subsequent treatment modalities. In 3 out of four patients, TBF was successfully treated by endoscopic stenting only. Five patients (38.5%) died following a septic course with multiple organ failure. The development of TBF after Ivor-Lewis esophagectomy is always combined with anastomotic leakage of the esophagogastrostomy. Treatment options primarily depend on the vascularization of the gastric conduit, the severity of the concomitant aspiration pneumonia, and the volume of the air leakage.