[Vibrio vulnificus, an increasing threat of sepsis in Germany?] / Vibrio vulnificus, eine zunehmende Sepsisgefahr in Deutschland?

BACKGROUND: The prevalence of Vibrio vulnificus heavily depends on the temperature and salinity of the sea water. In the course of climate change an increase in cases of fatal sepsis caused by V. vulnificus at the German Baltic Sea coast could be detected. OBJECTIVE: To generate awareness for a life-threatening infection with increasing incidence in Germany. MATERIAL AND METHODS: This article presents an overview of the current state of the literature followed by an exemplary description of cases with V vulnificus sepsis caused by contact with water in the Baltic Sea, which were treated at the Medical University in Greifswald in summer 2018. RESULTS: In the presence of risk factors, such as liver and kidney diseases, immunosuppression and male sex, there is a danger of severe sepsis if damaged skin comes into contact with contaminated sea water. A pronounced organ dysfunction can frequently be found on admission. In these cases the diagnosis must be made promptly and timely surgical cleansing and antibiotic treatment should be initiated (e.g. a combination of tetracyclines and third generation cephalosporins). CONCLUSION: Sepsis due to V. vulnificus will probably increase over the coming years. Because there is a latency in some cases between infection and onset of sepsis, physicians beyond the coastal region must also be informed about this disease.

[New challenges for intensive care medicine due to climate change and global warming]. / Neue intensivmedizinische Herausforderungen durch Klimawandel und globale Erderwärmung.

BACKGROUND: In the last five decades a continuous increase in the average global temperature has been recorded. Furthermore, natural disasters (e.g. heat waves, severe storms, floods and large forest fires) are becoming more frequent. The impact of global warming and climate change on health involves an increase in respiratory, cardiovascular, renal and cognitive mental diseases. Furthermore, a change in the frequency and patterns of infectious diseases can also be observed in Europe. MATERIAL AND METHODS: This article presents the most important studies that investigated diseases associated with the climate change, with special reference to those that represent a challenge for intensive care medicine. RESULTS: Currently available epidemiological data and statistical extrapolations indicate that diseases resulting from the climate change (acute infection-related respiratory and intestinal diseases, exacerbation of pre-existing pulmonary lesions, heat-related dehydration, cerebral insults and myocardial infarction) are relevant for intensive care medicine. Particular emphasis is placed on a significant increase in acute kidney damage during heat waves. A previously unknown pattern of infectious diseases necessitates new knowledge and targeted management. In some studies, persisting mental impairments were registered during heat waves and natural disasters, e.g. posttraumatic stress disorder. CONCLUSION: Intensive care medicine must be prepared for the challenges due to global warming and climate change. Slow but continuous changes (e.g. rise in temperature) as well as acute changes (e.g. heat waves and natural disasters) will induce an increased need for intensive medical care services (e.g. an increase in the need for renal replacement procedures). Intensive care physicians will need to be familiar with the diagnostics and management of diseases associated with the climate change. An initiative of the specialist societies involved would be welcomed.

Pathogen-specific antibody profiles in patients with severe systemic infections.

Infections are often caused by pathobionts, endogenous bacteria that belong to the microbiota. Trauma and surgical intervention can allow bacteria to overcome host defences, ultimately leading to sepsis if left untreated. One of the main defence strategies of the immune system is the production of highly specific antibodies. In the present proof-of-concept study, plasma antibodies against 9 major pathogens were measured in sepsis patients, as an example of severe systemic infections. The binding of plasma antibodies to bacterial extracellular proteins was quantified using a semi-automated immunoblot assay. Comparison of the pathogen-specific antibody levels before and after infection showed an increase in plasma IgG in 20 out of 37 tested patients. This host-directed approach extended the results of pathogen-oriented microbiological and PCR diagnostics: a specific antibody response to additional bacteria was frequently observed, indicating unrecognised poly-microbial invasion. This might explain some cases of failed, seemingly targeted antibiotic treatment.

Current clinical use of intravenous fosfomycin in ICU patients in two European countries.

PURPOSE: In Europe, intravenous fosfomycin (IV) is used particularly in difficult-to-treat or complex infections, caused by both Gram-positive and Gram-negative pathogens including multidrug-resistant strains. Here, we investigated the efficacy and safety of intravenous fosfomycin under real-life conditions. METHODS: Prospective, multi-center, and non-interventional study in patients with bacterial infections from 20 intensive care units (ICU) in Germany and Austria (NCT01173575). RESULTS: Overall, 209 patients were included (77 females, 132 males, mean age: 59 ± 16 years), 194 of which were treated in intensive care (APACHE II score at the beginning of fosfomycin therapy: 23 ± 8). Main indications (± bacteremia or sepsis) were infections of the CNS (21.5%), community- (CAP) and hospital-acquired pneumonia (HAP)/ventilator-associated pneumonia (VAP, 15.3%), bone and joint infections (BJI, 11%), abdominal infections (11%), and bacteremia (10.5%). Most frequently identified pathogens were S. aureus (22.3%), S. epidermidis (14.2%), Enterococcus spp. (10.8%), E. coli (12.3%) and Klebsiella spp. (7.7%). At least one multidrug-resistant (MDR) pathogen was isolated from 51 patients (24.4%). Fosfomycin was administered with an average daily dose of 13.7 ± 3.5 g over 12.4 ± 8.6 days, almost exclusively (99%) in combination with other antibiotics. The overall clinical success was favorable in 81.3% (148/182) of cases, and in 84.8% (39/46) of patients with ≥ 1 MDR pathogen. Noteworthy, 16.3% (34/209) of patients developed at least one, in the majority of cases non-serious, adverse drug reaction during fosfomycin therapy. CONCLUSION: Our data suggest that IV fosfomycin is an effective and safe combination partner for the treatment of a broad spectrum of severe bacterial infections in critically ill patients.

Impact of antibiotic administration on blood culture positivity at the beginning of sepsis: a prospective clinical cohort study.

OBJECTIVES: Sepsis guidelines recommend obtaining blood cultures before starting anti-infective therapy in patients with sepsis. However, little is known of how antibiotic treatment before sampling affects bacterial growth. The aim of this study was to compare the results of blood cultures drawn before and during antibiotic therapy. METHODS: Prospective clinical cohort study of septic patients. Adult intensive care unit patients with two or three blood culture sets at the beginning of sepsis between 2010 and 2017 were included. Patients with blood culture samples obtained before antibiotic therapy were compared with patients with samples taken during antibiotic therapy. Blood culture positivity, defined as presence of a microbiological pathogen, was compared between the groups. Logistic regression was performed to adjust the impact of different factors with respect to blood culture positivity. RESULTS: In total, 559 patients with 1364 blood culture sets at the beginning of sepsis were analysed. Blood culture positivity was 50.6% (78/154) among patients with sepsis who did not receive antibiotics and only 27.7% (112/405) in those who were already receiving antibiotics (p <0.001). Logistic regression revealed antibiotic therapy as an independent factor for less pathogen identification (odds ratio 0.4; 95% CI 0.3-0.6). Gram-positive pathogens (28.3% (111/392) versus 11.9% (116/972); p <0.001) and also Gram-negative pathogens (16.3% (64/392) versus 9.3% (90/972); p <0.001) were more frequent in blood culture sets drawn before antibiotic therapy compared with sets obtained during antibiotic therapy. CONCLUSIONS: Obtaining blood cultures during antibiotic therapy is associated with a significant loss of pathogen detection. This strongly emphasizes the current recommendation to obtain blood cultures before antibiotic administration in patients with sepsis.

[Sepsis detection in emergency medicine : Results of an interprofessional survey on sepsis detection in prehospital emergency medicine and emergency departments]. / Sepsis erkennen im Rettungsdienst : Ergebnisse einer interprofessionellen Befragung zur präklinischen und frühen innerklinischen Sepsiserkennung.

BACKGROUND: Sepsis is associated with a high mortality, which can be reduced by starting screening, diagnostics and treatment as early as possible. Due to multiple educational programs and increased awareness, a decreased sepsis mortality on intensive care units has been achieved. Many patients with sepsis are admitted by the prehospital emergency service to hospital emergency departments. Thus, prehospital emergency services and emergency departments provide an opportunity to start screening, diagnosis and treatment earlier. OBJECTIVES: To detect sepsis it is paramount that emergency personnel are aware of the disease and have a profound knowledge regarding symptoms, screening and diagnostics. The objective of this survey was to examine the state of knowledge regarding sepsis among staff working in emergency medicine. MATERIAL AND METHODS: To assess the awareness and knowledge, a paper-based, anonymous survey was conducted among prehospital and emergency department personnel from May to August 2017 in northeastern Germany. Testing of significance was carried out using the χ2-testand Fisher's exact test. RESULTS: Out of 411 persons polled 212 answered (response rate 51.6%) and 24 questionnaires were incomplete and thus excluded. A total of 188 questionnaires were included covering 55 emergency physicians, 23 nurses, 82 paramedics and 19 emergency dispatchers. On a 4-point Likert scale 100% of emergency doctors, 96% of nurses, 84% of paramedics and 84% of emergency dispatchers considered early initiation of sepsis treatment to be important. Additionally, 92% of emergency physicians and 65% of nurses had attended educational programs on sepsis within the last year, which is significantly higher than among paramedics (19%, p < 0.01) and emergency dispatchers (21%, p = 0.025). In addition, 38% of paramedics and 47% of emergency dispatchers had never attended lectures on sepsis. The quick sequential (sepsis-related) organ failure assessment (qSOFA) was known by 80% of emergency doctors, thus, significantly more often than by nurses (26%), paramedics (29%) and emergency dispatchers (29%, p < 0.01). The emergency personnel were asked to tick all symptoms they associated with sepsis from a display of 14 symptoms. Among all occupation groups the majority selected "increased body temperature", "drop in blood pressure" and "altered breathing". In relation to "increased body temperature" the symptom "altered mental status" was selected significantly more frequently by emergency doctors than by nurses and paramedics (p = 0.02 and p < 0.01, respectively). The combination of at least all 3 qSOFA parameters was selected significantly more often by emergency doctors (62%) than by nurses (13%) and paramedics (10%, p = 0.017 and p < 0.01, respectively). CONCLUSION: Although emergency personnel rated an early initiation of sepsis treatment as important, sepsis knowledge was limited. While the majority of emergency doctors and many nurses had attended educational programs on sepsis within the last year, an alarmingly high percentage of paramedics and emergency dispatchers had never received sepsis education. Emergency personnel are mostly unfamiliar with the qSOFA score and did not associate an altered mental status with sepsis. In light of the high sepsis morbidity and mortality, further achievements might be made by initiating sepsis screening and diagnostics in the prehospital setting. Analogous to advancements in intensive care units, increased educational programs for emergency personnel might lead to an earlier detection and improved prognosis of sepsis.

Continuing chronic beta-blockade in the acute phase of severe sepsis and septic shock is associated with decreased mortality rates up to 90 days.

BACKGROUND: There is growing evidence that beta-blockade may reduce mortality in selected patients with sepsis. However, it is unclear if a pre-existing, chronic oral beta-blocker therapy should be continued or discontinued during the acute phase of severe sepsis and septic shock. METHODS: The present secondary analysis of a prospective observational single centre trial compared patient and treatment characteristics, length of stay and mortality rates between adult patients with severe sepsis or septic shock, in whom chronic beta-blocker therapy was continued or discontinued, respectively. The acute phase was defined as the period ranging from two days before to three days after disease onset. Multivariable Cox regression analysis was performed to compare survival outcomes in patients with pre-existing chronic beta-blockade. RESULTS: A total of 296 patients with severe sepsis or septic shock and pre-existing, chronic oral beta-blocker therapy were included. Chronic beta-blocker medication was discontinued during the acute phase of sepsis in 129 patients and continued in 167 patients. Continuation of beta-blocker therapy was significantly associated with decreased hospital (P=0.03), 28-day (P=0.04) and 90-day mortality rates (40.7% vs 52.7%; P=0.046) in contrast to beta-blocker cessation. The differences in survival functions were validated by a Log-rank test (P=0.01). Multivariable analysis identified the continuation of chronic beta-blocker therapy as an independent predictor of improved survival rates (HR = 0.67, 95%-CI (0.48, 0.95), P=0.03). CONCLUSIONS: Continuing pre-existing chronic beta-blockade might be associated with decreased mortality rates up to 90 days in septic patients.

[New Sepsis-3 definition : Do we have to treat sepsis before we can diagnose it from now on?] / Neue SEPSIS-3-Definition : Müssen wir Sepsis in Zukunft behandeln, bevor wir sie diagnostizieren dürfen?

The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) have been available since the beginning of 2016. SEPSIS-3 completely replaces the old SIRS criteria in the definition of sepsis and defines sepsis from now on as "life-threatening organ dysfunction caused by a dysregulated host response to infection". However, it seems questionable whether in clinical practice the new definition is really superior to the old one. The most important question is the following: Is it helpful to have a definition that first recognizes a patient once organ dysfunction has occurred and the patient already needs intensive care?

Short time impact of different hydroxyethyl starch solutions on the mesenteric microcirculation in experimental sepsis in rats.

BACKGROUND: Fluid resuscitation plays a crucial role in the therapy of severe sepsis and septic shock. The use of colloids in sepsis is controversial at present. The aim of our study was to evaluate the effects of second and third generation colloids on the mesenteric microcirculation in early experimental sepsis. METHODS: Male Lewis rats (n=64) were used. Animals underwent sham surgery or colon ascendens stent insertion for sepsis induction by peritonitis. Sixteen hours after the surgery animals were randomly assigned to receive one of the following fluid regimens intravenously: 16ml/kg Ringer's lactate, 64ml/kg Ringer's lactate, 16ml/kg 130/0.4 hydroxyethyl starch, and 16ml/kg 200/0.5 hydroxyethyl starch. Intravital microscopy of the mesenteric microcirculation (plasma extravasation; leukocyte-endothelial interactions) and arterial blood gas analysis were performed before and after fluid resuscitation. RESULTS: In animals with experimental sepsis plasma extravasation was significantly increased compared to control animals (p<0.05). There were no significant differences in plasma extravasation between septic animals receiving crystalloids and or colloid. Furthermore, the type of administered fluid did not influence the number of adhering leucocytes during the observation period. CONCLUSION: The short time impact of different hydroxyethyl starch solutions on the microcirculation of the mesentery is not different from crystalloids in colon ascendens stent peritonitis-induced experimental sepsis in rats.

Impact of antibiotics on the microcirculation in local and systemic inflammation.

The main function of antibiotics is related to their capacity to eliminate a microorganism. In addition to the antimicrobial function of antibiotics, they are known to have anti-inflammatory and vasomodulatory effects on the microcirculation. The ability of non-antimicrobial derivatives of antibiotics to control inflammation illustrates the distinct anti-microbial and anti-inflammatory roles of antibiotics. In this review, we discuss the impact of antibiotics on leukocyte recruitment and the state of the microcirculation. Literature reporting the effect of antibiotics in non-infectious inflammatory conditions is reviewed as well as the studies demonstrating the anti-inflammatory effects of antibiotics in animal models of infection. In addition, the effect of the antibiotics on the immune system is summarized in this review, in order to postulate some mechanisms of action for the proand anti-inflammatory contribution of antibiotics. Literature reported the effect of antibiotics on the production of cytokines, chemotaxis and recruitment of leukocytes, production of reactive oxygen species, process of phagocytosis and autophagy, and apoptosis of leukocytes. Yet, all antibiotics may not necessarily exert an anti-inflammatory effect on the microcirculation. Thus, we suggest a model for spectrum of anti-inflammatory and vasomodulatory effects of antibiotics in the microcirculation of animals in local and systemic inflammation. Although the literature suggests the ability of antibiotics to modulate leukocyte recruitment and microperfusion, the process and the mechanism of action are not fully characterized. Studying this process will expand the knowledge base that is required for the selection of antibiotic treatment based on its anti-inflammatory functions, which might be particularly important for critically ill patients.

[Prevention of infections under anesthetic breathing with breathing filters: concerted recommendations of the Deutsche Gesellschaft für Krankenhaushygiene e.V. (DGKH) and the Deutsche Gesellschaft für Anästhesiologie und Intensivmedizin e.V. (DGAI)]. / Infektionsprävention bei der Narkosebeatmung durch Einsatz von Atemsystemfiltern: Gemeinsame Empfehlung der Deutschen Gesellschaft für Krankenhaushygiene e.V. (DGKH) und der Deutschen Gesellschaft für Anästhesiologie und Intensivmedizin e.V. (DGAI).

An interdisciplinary working group from the German Society of Hospital Hygiene (DGKH) and the German Society for Anesthesiology and Intensive Care (DGAI) worked out the following recommendations for infection prevention during anesthesia by using breathing system filters (BSF). The BSF shall be changed after each patient. The filter retention efficiency for airborne particles is recommended to be >99% (II). The retention performance of BSF for liquids is recommended to be at pressures of at least 60 hPa (=60 mbar) or 20 hPa above the selected maximum ventilation pressure in the anesthetic system.The anesthesia breathing system may be used for a period of up to 7 days provided that the functional requirements of the system remain unchanged and the manufacturer states this in the instructions for use. The breathing system and the manual ventilation bag are changed immediately after the respective anesthesia if the following situation has occurred or it is suspected to have occurred: Notifiable infectious disease involving the risk of transmission via the breathing system and the manual bag, e.g. tuberculosis, acute viral hepatitis, measles, influenza virus, infection and/or colonization with a multi-resistant pathogen or upper or lower respiratory tract infections. In case of visible contamination e.g. by blood or in case of defect, it is required that the BSF and also the anesthesia breathing system is changed and the breathing gas conducting parts of the anesthesia ventilator are hygienically reprocessed.Observing of the appropriate hand disinfection is very important. All surfaces of the anesthesia equipment exposed to hand contact must be disinfected after each case.

Prevention, diagnosis, therapy and follow-up care of sepsis: 1st revision of S-2k guidelines of the German Sepsis Society (Deutsche Sepsis-Gesellschaft e.V. (DSG)) and the German Interdisciplinary Association of Intensive Care and Emergency Medicine (Deutsche Interdisziplinäre Vereinigung für Intensiv- und Notfallmedizin (DIVI)).

Practice guidelines are systematically developed statements and recommendations that assist the physicians and patients in making decisions about appropriate health care measures for specific clinical circumstances taking into account specific national health care structures. The 1(st) revision of the S-2k guideline of the German Sepsis Society in collaboration with 17 German medical scientific societies and one self-help group provides state-of-the-art information (results of controlled clinical trials and expert knowledge) on the effective and appropriate medical care (prevention, diagnosis, therapy and follow-up care) of critically ill patients with severe sepsis or septic shock. The guideline had been developed according to the "German Instrument for Methodological Guideline Appraisal" of the Association of the Scientific Medical Societies (AWMF). In view of the inevitable advancements in scientific knowledge and technical expertise, revisions, updates and amendments must be periodically initiated. The guideline recommendations may not be applied under all circumstances. It rests with the clinician to decide whether a certain recommendation should be adopted or not, taking into consideration the unique set of clinical facts presented in connection with each individual patient as well as the available resources.

Glutamine and alanyl-glutamine dipeptide reduce mesenteric plasma extravasation, leukocyte adhesion and tumor necrosis factor-α (TNF-α) release during experimental endotoxemia.

Glutamine (GLN) appears to be an essential nutrient during organism development and critical illness. The aim of our study was to evaluate the effects of GLN and its generic preparation alanyl-glutamine-dipeptide (DIP) on the microcirculation in endotoxemia in rats and its effects on tonus or aortal rings in vitro. Male Lewis rats (n=40) were separated in 4 groups. Group 1 (CON) served as healthy control group while the other groups received an endotoxin bolus i.v. (5 mg/kg lipopolysaccharide, LPS i.v.). In group 3 (LPS+GLN) 0.75 g/kg-1 GLN i.v. before LPS challenge was administered. In group 4 (LPS+DIP) DIP containing 0.75 g/kg GLN was given. Leukocyte-endothelial interactions and mesenteric plasma extravasation were determined at 0, 1 and 2 hours during the experiment by intravital fluorescence microscopy (IVM). Cytokine release (TNF-alpha, IL-1 beta, IL-6, IL-10) was measured by ELISA. GLN treatment reduced leukocyte adherence (-49.7% vs. LPS group, p<0.05) and plasma extravasation (-12.3% vs. LPS group, p<0.05) significantly during endotoxemia compared to untreated LPS animals. In group 4 (DIP+LPS), a decrease of leukocyte adherence (-56.0%) and mesenteric plasma extravasation (-18.8% vs. LPS group, p<0.05) was also found. TNF-alpha levels were reduced in both GLN and DIP (p<0.05). In vitro experiments demonstrated that glutamine agents could attenuate the response to contracting agents in presence of the vascular endothelium, implying nitric oxide pathway. In vivo, GLN as well as DIP pre-treatment diminish the detrimental impact of endotoxemia on the mesenteric microcirculation and the TNF-alpha release, the effects whose clinical importance should be further examined.

Response of the rat intestinal microcirculation to experimental endotoxemia is attenuated by ampicillin but not by its derivative KKP723.

KKP723 (KKP), a derivative of ampicillin, is a newly developed beta-lactam antibiotic. Using an experimental endotoxemia model, the intestinal microcirculation in four groups of animals were evaluated using intravital microscopy (IVM). The groups included were a control group, an endotoxemic group (15 mg/kg i.v. LPS from E. coli), an ampicillin (50 mg/kg i.v.) treated endotoxemic group and an endotoxemic group treated with KKP (67.4 mg/kg i.v.). Ampicillin treatment resulted in a significant reduced number of firmly adhering leukocytes in intestinal submucosal venules. KKP treatment did not show this effect on leukocyte activation. We found no changes of the functional capillary density (FCD) of the intestinal wall by treatment with ampicillin or its derivative KKP. The increased leukocyte adherence in the KKP treated LPS animals may be explained by a loss of a possible ampicillin-related anti-inflammatory effect by the biotransformation process. The endotoxemia IVM model is useful to detect effects of antibiotics in an impaired microcirculation.

Ketamine does not affect intestinal microcirculation in pentobarbital-anaesthetized rats during experimental endotoxaemia.

The objective of the study was to evaluate the effects of ketamine on intestinal microcirculation in pentobarbital-anaesthetized rats during experimental endotoxaemia. A prospective, randomized, controlled study was carried out using 32 male Lewis rats. The animals were divided into four groups (n = 8 each). All animals were initially anaesthetized with 60 mg/kg pentobarbital (i.p.). Group 1 served as a control (18.5 mg/kg/h pentobarbital i.v.). Groups 2 and 4 received an endotoxin intravenous infusion of 15 mg/kg lipopolysaccharide (LPS) from Escherichia coli. Groups 3 and 4 also received 10 mg/kg/h ketamine (i.v.). After 2 h of observation, the animals were examined for intestinal functional capillary density (FCD) and leukocyte adherence to the venular endothelium by means of intravital fluorescence microscopy (IVM). Subsequent to this examination, blood samples were collected to determine release of the cytokines tumour necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6 and IL-10. Endotoxaemia tended to decrease intestinal FCD (mucosa: -10.1%, muscularis longitudinalis: -2%, muscularis circularis: -9.8%) and significantly increase leukocyte adherence within submucosal venules (collecting venules: +133%, postcapillary venules: +207%; P<0.05). TNF-alpha, IL-1beta, IL-6 and IL-10 levels were significantly elevated following endotoxin challenge. The addition of ketamine to pentobarbital anaesthesia did not significantly affect FCD, leukocyte behaviour or cytokine levels. In conclusion, intravenous pentobarbital anaesthesia with the additional administration of ketamine did not cause alterations within the microcirculation or changes in cytokine release during endotoxaemia. In rats, the combination of pentobarbital and ketamine is suitable for use during the study of intestinal microcirculation in experimental endotoxaemia.