Sebastian Decker

Relevance of Candida and other mycoses for morbidity and mortality in severe sepsis and septic shock due to peritonitis.

This single‐centre retrospective cohort study evaluated the incidence and outcome of mycoses in critical ill patients (n = 283) with sepsis due to peritonitis. Overall mortality was 41.3%, and the 28‐day mortality was 29.3%. Fungal pathogens were found in 51.9%. The common first location was the respiratory tract (66.6%), followed by the abdominal site (19.7%). Candida colonisation was found in 64.6%, and invasive Candida infection in 34.0%. Identified fungi were Candida spp. in 98.6% and Aspergillus spp. in 6.1%. Patients with fungal pathogens showed a higher rate of postoperative peritonitis, APACHE II and tracheotomy. In comparison to patients without fungal pathogens, these patients showed a longer duration on mechanical ventilation, and a higher overall mortality. Patients with Candida‐positive swabs from abdominal sites had more fascia dehiscence and anastomosis leakage. Seventy‐two patients (48.9%) received antifungal therapy, 26 patients were treated empirically. Antifungal therapy was not associated with a decrease in mortality. Age and renal replacement therapy were associated with mortality. In conclusion, fungi are common pathogens in critically ill patients with peritonitis, and detection of fungi is associated with an increase in overall mortality. Particularly, Candida‐positive abdominal swabs are associated with an increase in morbidity. However, we were not able to demonstrate a survival benefit for antifungal therapy in peritonitis patients.

Reduced Serum Butyrylcholinesterase Activity Indicates Severe Systemic Inflammation in Critically Ill Patients

Systemic inflammation is an immune response to a nonspecific insult of either infectious or noninfectious origin and remains a challenge in the intensive care units with high mortality rate. Cholinergic neurotransmission plays an important role in the regulation of the immune response during inflammation. We hypothesized that the activity of butyrylcholinesterase (BChE) might serve as a marker to identify and prognose systemic inflammation. By using a point-of-care-testing (POCT) approach we measured BChE activity in patients with severe systemic inflammation and healthy volunteers. We observed a decreased BChE activity in patients with systemic inflammation, as compared to that of healthy individuals. Furthermore, BChE activity showed an inverse correlation with the severity of the disease. Although hepatic function has previously been found essential for BChE production, we show here that the reduced BChE activity associated with systemic inflammation occurs independently of and is thus not caused by any deficit in liver function in these patients. A POCT approach, used to assess butyrylcholinesterase activity, might further improve the therapy of the critically ill patients by minimizing time delays between the clinical assessment and treatment of the inflammatory process. Hence, assessing butyrylcholinesterase activity might help in early detection of inflammation.

Immune-Response Patterns and Next Generation Sequencing Diagnostics for the Detection of Mycoses in Patients with Septic Shock—Results of a Combined Clinical and Experimental Investigation

Fungi are of increasing importance in sepsis. However, culture-based diagnostic procedures are associated with relevant weaknesses. Therefore, culture- and next-generation sequencing (NGS)-based fungal findings as well as corresponding plasma levels of β-d-glucan, interferon gamma (INF-γ), tumor necrosis factor alpha (TNF-α), interleukin (IL)-2, -4, -6, -10, -17A, and mid-regional proadrenomedullin (MR-proADM) were evaluated in 50 septic patients at six consecutive time points within 28 days after sepsis onset. Furthermore, immune-response patterns during infections with Candida spp. were studied in a reconstituted human epithelium model. In total, 22% (n = 11) of patients suffered from a fungal infection. An NGS-based diagnostic approach appeared to be suitable for the identification of fungal pathogens in patients suffering from fungemia as well as in patients with negative blood cultures. Moreover, MR-proADM and IL-17A in plasma proved suitable for the identification of patients with a fungal infection. Using RNA-seq., adrenomedullin (ADM) was shown to be a target gene which is upregulated early after an epithelial infection with Candida spp. In summary, an NGS-based diagnostic approach was able to close the diagnostic gap of routinely used culture-based diagnostic procedures, which can be further facilitated by plasmatic measurements of MR-proADM and IL-17A. In addition, ADM was identified as an early target gene in response to epithelial infections with Candida spp.

A Sustained Reduction in Serum Cholinesterase Enzyme Activity Predicts Patient Outcome following Sepsis

Early sepsis identification is of paramount importance for an effective therapy and the patient outcome; however, a suitable prognostic biomarker is lacking. Anti-inflammatory nonneuronal cholinergic signaling modulates the magnitude of an immune response. Serum cholinesterase (BChE), an enzyme that hydrolyzes acetylcholine, plays an important role during inflammatory response and serves as an accurate index of cholinergic activity. BChE activity was measured in septic patients using a point-of-care system, and levels of conventional inflammatory markers and the disease severity scores were obtained. We observed a strong, sustained reduction in BChE activity in patients who died within a 90-day observation period, as compared to survivors. Reduced BChE activity when measured at the ICU admission effectively differentiated between the 90-day survivor and the nonsurvivor patient groups. We estimated a critical BChE level of 1.661 kU/L (CI 0.5–0.8, 94% sensitivity, 48% specificity, AUC 0.7) to best predict patient outcome providing a benchmark criterion for early detection of potentially fatal sepsis measured at the admission. This finding suggests that the BChE activity, used in combination with the laboratory tests, clinical examination, and the disease severity scoring, could serve to identify high-risk patients at the ICU admission, the most critical time point in the sepsis treatment.

New Approaches to Anti-infective Treatment of Ventilator-Associated Respiratory Infections caused by Pseudomonas aeruginosa

Study background: The purpose of this study was to evaluate recent strategies for anti-infective treatment in patients suffering from ventilator-associated respiratory infections caused by P. aeruginosa and to assess the riskbenefit profile of inhaled tobramycin.Methods: Electronic health records of patients suffering from respiratory infections caused by P. aeruginosa from 2011-2014 were retrospectively screened.Results: In 81 patients, P. aeruginosa was found in respiratory secretions, of which 26 patients suffered from ventilator-associated pneumonia (VAP), whereas 55 patients only fulfilled criteria of ventilator-associated tracheitis (VAT). Inhaled tobramycin was used in 14 patients with VAP and 31 patients with VAT. In this context, inhaled tobramycin was shown to be safe (e.g. no bronchoconstriction or systemic toxicity) and did not result in an increase of tobramycin resistant strains in respiratory secretions at 90 days following study inclusion. However, a clear clinical benefit (e.g. reduced need for i.v. antibiotics) could not be shown.\Conclusion: Inhaled tobramycin was shown to be a suitable approach with a favorable risk profile to treat patients suffering from respiratory infections (VAP, VAT) caused by P. aeruginosa. The clinical benefit needs to be reevaluated in a larger prospective investigation.