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.

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.

[Therapy escalation for the potential organ donor : Are all intensive care measures also ethically justifiable?] / Therapieeskalation beim potenziellen Organspender : Sind alle intensivmedizinischen Maßnahmen auch ethisch zu rechtfertigen?

The gap between the number of organs needed and the number available has dramatically increased in Germany in the last decade-for intensivists and transplantation specialists, it is challenging to cover the demand responsibly. It is therefore increasingly important to identify potential organ donors in order to realize organ donation. An escalation of intensive care measures is often required, which raises critical ethical questions. In Germany, organ donation is only allowed after brain death with prior informed consent from the deceased or his/her relatives. Determining the willingness of the potential organ donor and adapting the subsequent intensive care to it requires experience and empathy. Therapy escalation for the realization of organ donation is not opposed to the basic ethical principles of medicine, but remains an individual decision. A time limitation of this last intensive therapy phase to achieve optimal conditions for transplantation should be discussed with the relatives and adapted to the medical requirements. This article would like to highlight ethical questions that are relevant in the context of therapy escalation of potential organ donors and, thus, support the decision-making process.

[Critical care management of the potential organ donor : Current recommendation for adults]. / Intensivmedizinisches Management des potentiellen Organspenders : Aktuelle Empfehlungen für Erwachsene.

The shortage of donor organs has not improved in recent years. To increase the number and success of transplantation it is crucial to optimize the processes of early identification of potential organ donors and structured critical care management. The therapy starts long before brain death is diagnosed. Structured in-house organ donor management protocols ensure a highly qualified critical care that has a direct impact on the transplantation outcome. The therapy is based on the established standards. The main focus is on differentiated catecholamine and volume therapy. Vasopressin, in combination with norepinephrine, is effective for both treating vasoplegia and electrolyte disturbances. Despite poor evidence, steroids are useful for stabilizing hemodynamics and treating the consequences of neuroendocrine dysfunction. Overall, prospective studies are required to give general recommendations for critical care.

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.

[Overwhelming postsplenectomy infection syndrome]. / Fulminante Pneumokokkensepsis nach Splenektomie.

The overwhelming postsplenectomy infection syndrome (OPSI) is a fulminant sepsis that is mainly caused by Streptococcus pneumoniae and is characterized by a particular high mortality. Patients whose spleen was removed due to a hematological disease are at special risk. Even after the recommended immunization against Streptococcus pneumoniae 20-30 % of these patients do not develop an adequate level of antibody response. Therefore, this particular group of patients must be trained how to behave in case of fever and need to obtain immediate specific sepsis therapy with antibiotic prophylaxis.

Serum osmolality and outcome in intensive care unit patients.

BACKGROUND: The aim of the present study was to compare 16 routine clinical and laboratory parameters, acute physiologic and chronic health evaluation (APACHE) and sequential organ failure assessment (SOFA) score for their value in predicting mortality during hospital stay in patients admitted to a general intensive care unit (ICU). METHODS: A retrospective observational clinical study was carried out in a 15-bed ICU in a university hospital. Nine hundred and thirty-three consecutive patients with ICU stay > 24 h (36.2% surgical, 29.1% medical and 34.7% trauma) were observed. Blood sampling, patient surveillance and data collection were performed. The primary outcome was mortality in the hospital. We used receiver operating characteristic (ROC) analyses and logistic regression to compare the 16 relevant parameters, APACHE II and SOFA scores. RESULTS: Two hundred and thirty-three out of the 933 patients died (mortality 25.0%). One laboratory parameter, serum osmolality [area under the curve (AUC) 0.732] had a predictive value for mortality which lay between that of APACHE II (AUC 0.784) and SOFA (AUC 0.720) scores. When outcome prediction was restricted to long-term patients (ICU stay > 5 days), serum osmolality (AUC 0.711) performed better than either of the standard scores (APACHE AUC 0.655, SOFA AUC 0.636). Using logistic regression analysis, the association of clinical parameters, age and diagnosis group with mortality was determined. CONCLUSION: Elevated serum osmolality at ICU admission is associated with an increased mortality risk in critically ill patients. Serum osmolality is cheaper and more rapid to determine than the scoring systems. However, further studies are needed to evaluate the predictive value of serum osmolality in different patient populations.

[PercuTwist dilational tracheostomy. Prospective evaluation of 54 consecutive patients]. / PercuTwist-Dilatationstracheotomie. Prospektive Evaluation an 54 konsekutiven Patienten.

BACKGROUND: Percutaneous dilational tracheostomy (PDT) is considered to be an accepted method in intensive care patients. In 2002 Frova and Quintel described a method of dilation that employed controlled rotation of the PercuTwist dilational device. The goal of the present study was to evaluate the new technique employed by an experienced team. PATIENTS AND METHODS: Prospective, observational clinical study in 54 intensive care patients who required PDT. All tracheostomies were accompanied by bronchoscopic control. Vital parameters and perioperative complications were registered. RESULTS: In all 54 consecutive PercuTwist tracheostomies no severe complications were noted. Accidental tracheal ring fracture was noted in 7 patients while bleeding that needed surgical care occurred in 1 patient. CONCLUSION: The PercuTwist tracheostomy is a safe procedure for intensive care patients. More prospective studies that would compare the PercuTwist tracheostomy with the other PDT methods are necessary.

[Application of the laryngeal mask for elective percutaneous dilatation tracheotomy]. / Anwendung der Larynxmaske für die elektive perkutane Dilatationstracheotomie.

Percutaneous dilatational tracheostomy is an increasingly accepted procedure for bed-side tracheostomy. The exact positioning of the endotracheal tube, the localization of the point for puncturing the trachea and damage to the endotracheal tube and the cuff as well as to the bronchoscope due to the puncturing process are technical problems which can endanger the course of the operation. In a prospective randomized study, we examined whether use of the laryngeal mask airway (LMA) is a real alternative to the endotracheal tube during tracheostomy. Of 48 consecutive patients only 43 fulfilled all criteria for this study: PaO2 > 100 mmHg, PaCO2 < 45 mmHg (in patients with head injury < 35 mmHg) under intermittent positive pressure ventilation (IPPV) with a mean ventilation pressure of < 25 mmHg and an FiO2 of 1.0. Patients with intestinal obstruction, hemorrhages of the mouth and nose and unfavourable anatomic conditions were not included in this study. Three more patients had to be excluded from the study because of technical problems. In 21 patients tracheostomy was performed using an endotracheal tube (ET group) and in 19 patients using a LMA (LM group). After positioning of the endotracheal tube or the LMA, tracheostomy was performed in the usual way. Arterial blood gases (PaO2 and PaCO2) were investigated before positioning of the endotracheal tube or the LMA, five minutes after this procedure and five minutes after the end of tracheostomy. Mean arterial pressure (MAP), heart frequency (HF) and peripheral oxygen saturation (SpO2), endexpiratory CO2 partial pressure (PetCO2) and minute ventilation volume (MVV) were registered every 60 seconds. The ET group and LM group did not differ regarding basic diseases, age and severity of illness. Before the beginning of tracheostomy, there were no differences in MAP, HF, SpO2, PetCO2 and PaCO2 between the two groups. Before tracheostomy, only PaO2 was significantly higher in the LM group than in the ET group. Immediately before the insertion of the tracheal cannula and five minutes after the end of tracheostomy, there were no differences in the measured parameters of the two groups. An increase in PetCO2 and a decrease in minute ventilation volume were observed in both groups. Regarding technical complications, the LMA is a safe alternative to the endotracheal tube. The choice of method should depend on the basic disease and the patient's ventilation requirements at the time of tracheostomy, while there is still a call for safe instruments guaranteeing sufficient sealing of the respiratory tract during the dilatational tracheostomy and simultaneous avoidance of technical problems during puncturing of the trachea and widening of the point of puncturing.

The specificity and affinity of polyclonal antibodies raised in rabbits against a hapten conjugated to rabbit serum albumin.

In this study, rabbit antisera to hapten-rabbit serum albumin conjugates were investigated regarding antibody titer, affinity, specificity, and affinity distribution. Methyl phosphonic acid p-amino-phenyl 1,2,2-trimethylpropyldiester (MATP) served as model hapten. Four MATP-rabbit serum albumin conjugates with various hapten densities (with and without spacer) were synthesized and used for immunization of rabbits. Antisera were collected over a 130 day-period and characterized with different ELISA methods. We found that immunogens with rabbit serum albumin gave antisera with lower titers, but similar affinity as compared to polyclonal or monoclonal antibodies obtained with non-rabbit protein as carrier protein. Immunogens with a low hapten density led to higher final titers without affecting antibody affinity or specificity. Immunogens containing a bridging group resulted in higher antibody affinity with a changed specificity. The pattern of antibody affinity distribution differed considerably among individual rabbits and showed a non-Gaussian subpopulation distribution.