This is the fifth chapter of the guideline "Calculated initial parenteral treatment of bacterial infections in adults - update 2018" in the 2nd updated version. The German guideline by the Paul-Ehrlich-Gesellschaft für Chemotherapie e.V. (PEG) has been translated to address an international audience. It provides recommendations for the empirical and targeted antimicrobial treatment of lower respiratory tract infections, with a special emphasis on the treatment of acute exacerbation of COPD, community-acquired pneumonia and hospital-acquired pneumonia.

This is the fifth chapter of the guideline “Calculated initial parenteral treatment of bacterial infections in adults – update 2018” in the 2 updated version. The German guideline by the Paul-Ehrlich-Gesellschaft für Chemotherapie e.V. (PEG) has been translated to address an international audience.It provides recommendations for the empirical and targeted antimicrobial treatment of lower respiratory tract infections, with a special emphasis on the treatment of acute exacerbation of COPD, community-acquired pneumonia and hospital-acquired pneumonia.

Purpose Besides the established biomarker NT-proBNP, the new cardiovascular biomarkers MR-proANP, MR-proADM, Copeptin, and CT-proET-1 are promising to evaluate hemodynamics, exercise parameters, and prognosis in patients with pulmonary hypertension (PH).Methods 125 consecutive patients with pulmonary arterial hypertension (PAH) or chronic thromboembolic pulmonary hypertension (CTEPH) were prospectively enrolled at five German PH centers. Blood samples were taken during right heart catheterization. The primary study endpoint was the correlation between biomarkers and hemodynamic and exercise parameters. As secondary endpoint, prediction of 1-year mortality was evaluated.Results MR-proADM showed the strongest correlations with 6MWD and VO(2)peak, whereas NT-proBNP showed the strongest correlations with PVR, PAPm, and CI. In multivariate analysis, only MR-proADM was independently associated with exercise variables, whereas only NT-proBNP independently predicted hemodynamic parameters. All biomarkers were associated with 1-year survival, with MR-proADM showing the highest C index of 0.78. In multivariate analysis, MR-proADM predicted survival independent of age, 6-MWD, CI, RAP, and NT-proBNP. The cut-off of 1.08 nmol/l provided a sensitivity of 83 % and specificity of 66 %.Conclusions Different biomarkers reflect distinctive disease aspects in PH. NT-proBNP best predicts hemodynamic impairment while MR-proADM strongly correlates with exercise capacity. Additionally, MR-proADM represents a promising new marker to evaluate prognosis in patients with PAH and CTEPH. Multi-marker strategies should further be evaluated.

After introduction of the new international guidelines on idiopathic pulmonary fibrosis (IPF) in 2011, we investigated clinical management practices for patients with IPF according to physicians' diagnoses. A prospective, multicenter, noninterventional study with comprehensive quality measures including on-site source data verification was performed in Germany. 502 consecutive patients (171 newly diagnosed, 331 prevalent; mean± sd age 68.7±9.4 years, 77.9% males) with a mean disease duration of 2.3±3.5 years were enrolled. IPF diagnosis was based on clinical assessments and high-resolution computed tomography (HRCT) in 90.2%, and on surgical lung biopsy combined with histology in 34.1% (lavage in 61.8%). The median 6-min walk distance was 320 m (mean 268±200 m). The mean forced vital capacity was 72±20% pred and diffusing capacity of the lung for carbon monoxide was 35±15% pred. No drugs were administered in 17.9%, oral steroids in 23.7%, N -acetylcysteine in 33.7%, pirfenidone in 44.2% and other drugs in 4.6% of patients. Only 2.8% of the cohort was listed for lung transplantation. IPF patients were diagnosed in line with the new guidelines. They had more severe disease than those enrolled in recent randomised controlled trials. In addition to HRCT, the frequency of lung biopsies was surprisingly high. Treatment patterns varied substantially.

The objective of this prospective study was to evaluate the impact of exercise capacity, mental disorders, and hemodynamics on quality-of-life (QoL) parameters in patients with pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH).

BACKGROUND:Several biomarkers and prognostic scores have been evaluated to predict prognosis in community-acquired pneumonia (CAP). Optimal risk stratification remains to be evaluated. The aim of this study was to evaluate serum cortisol as biomarker for the prediction of adverse outcomes independently of the CRB-65 score und inflammatory biomarkers in a large cohort of hospitalised patients with CAP.METHODS:984 hospitalised CAP-patients were included. Serum cortisol was measured and its prognostic accuracy compared to the CRB-65 score, leucocyte count and C-reactive protein. Predefined endpoints were 30-day mortality and the combined endpoint critical pneumonia, defined as presence of death occurring during antibiotic treatment, mechanical ventilation, catecholamine treatment or ICU admission.RESULTS:64 patients died (6.5%) and 85 developed critical pneumonia (8.6%). Cortisol levels were significantly elevated in both adverse outcomes (p < 0.001) and predicted mortality (AUC 0.70, cut-off 795 nmol/L) and critical pneumonia (AUC 0.71) independently of all other measured variables after logistic regression analysis (p = 0.005 and 0.001, respectively). Prognostic accuracy of CRB-65 was significantly improved by adding cortisol levels (combined AUC 0.81 for both endpoints). In Kaplan-Meier analysis, cortisol predicted survival within different CRB-65 strata (p = 0.003). In subgroup analyses, cortisol independently predicted critical pneumonia when compared to procalcitonin, the CURB65 score and minor criteria for severe pneumonia according to the 2007 ATS/IDSA-guideline.CONCLUSION:Cortisol predicts mortality and critical disease in hospitalised CAP-patients independently of clinical scores and inflammatory biomarkers. It should be incorporated into trials assessing optimal combinations of clinical criteria and biomarkers to improve initial high risk prediction in CAP.

BACKGROUND:The purpose of this study was to evaluate the prevalence and outcomes of pulmonary hypertension in chronic hypersensitivity pneumonitis and to examine the relationship between pulmonary function tests and pulmonary hypertension.METHODS:We conducted a retrospective review of 120 patients with hypersensitivity pneumonitis seen at two centers for pulmonary diseases over a 5-year interval and identified patients with chronic hypersensitivity pneumonitis for whom both pulmonary function tests and Doppler echocardiography data were available.RESULTS:Chronic hypersensitivity pneumonitis was identified in 83 patients and Doppler echocardiography data were available for 73 of them. Pulmonary hypertension (sPAP ≥ 50 mmHg) was detected in 14 patients (19%), and was associated with a greater risk of death (median survival = 23 months vs. 98 months; P=0.003). Patients with pulmonary hypertension were older and had a significantly decreased PaO(2). There was a weak correlation between pulmonary function parameters and the underlying sPAP, with significance for FVC, FEV(1), and PaO(2) and inversely with PaCO(2).CONCLUSIONS:Using Doppler echocardiography for evaluation, pulmonary hypertension seems to be common in patients with chronic hypersensitivity pneumonitis, significantly impacts survival, and correlates with FVC, FEV(1), and PaO(2) and inversely with PaCO(2).

Einleitung: Das Krankheitsbild der morbiden Adipositas wird durch mehrere Symptom-komplexe verschiedener medizinischer Fachgebiete definiert, diagnostiziert und behandelt. Aktuell werden 7% der Gesundheitskosten in Deutschland durch adipositasassoziierte Erkrankungen verursacht. Seit 2009 werden ca. 35 Patienten mit morbider Adipositas (BMI >40 und begleitender ventilatorischer Insuffizienz) durch das Adipositaszentrum Dresden – Neustadt, dem Fachkrankenhaus Coswig und der Selbsthilfegruppe „Die Mollybetiker Dresden“ e.V. gemeinsam behandelt. Exemplarisch wird die Normalisierung von Funktionsparametern an einem Beispiel dargestellt nach Durchführung einer bariatrischen Therapie.

Schlusselworter ● ▶ Ambrisentan ● ▶ Leberzirrhose ● ▶ portopulmonale Hypertonie ● ▶ pulmonale Hypertonie

Rationale: The aim was to evaluate serum cortisol as biomarker for the prediction of adverse outcomes independently of the CRB-65 score und inflammatory biomarkers in a large cohort of hospitalised CAP-patients. Methods: 984 hospitalised CAP-patients from the CAPNETZ study cohort were included. Serum cortisol was measured and its prognostic accuracy compared to the CRB-65 score, leukocyte count and C-reactive protein. Predefined endpoints were 30-day mortality and development of critical pneumonia. Results: 64 patients died (6.5%) and 85 developed critical pneumonia (8.6%). Cortisol levels were significantly elevated in both adverse outcomes (p Conclusion: Cortisol predicts mortality and critical disease in hospitalised CAP-patients independently of clinical factors and inflammatory biomarkers. It represents a promising biomarker to complete the available panel of inflammatory, cardiovascular and other biomarkers for risk prediction and should be incorporated into trials assessing optimal combinations of clinical criteria and biomarkers to improve high risk prediction in CAP.

Die schwere, ambulant erworbene Pneumonie hat seit Jahrzehnten unverändert eine hohe Letalität trotz der medizinischen Fortschritte in Bezug auf intensivmedizinisches Management, antimikrobielle Therapie, Diagnostik und adjunktive Maßnahmen. Sie stellt für den betagten Patienten mit schweren Begleiterkrankungen, aber insbesondere für den jüngeren Patienten ohne erkennbare Grunderkrankung oder Abwehrschwäche eine Bedrohung dar, da annähernd die Hälfte der Erkrankten diese Infektion nicht überleben wird. Entscheidend für die Prognose der Patienten ist das rasche Erkennen der Erkrankung, die Risikoeinteilung nach dem CRB-65-Score, der umgehende Beginn einer adäquaten risikoadjustierten Antibiotikatherapie und die Einleitung weiterer adjunktiver Maßnahmen wie Sauerstoffgabe und nichtinvasive/invasive Beatmung. Die Diagnostik darf den Beginn der Antibiotikabehandlung nicht verzögern. Für die empirische Therapie mit Antibiotika ist die Einteilung nach dem individuellen Pseudomonas-Risiko entscheidend. In jedem Fall muss die antimikrobielle Behandlung gegen Pneumokokken wirksam sein; eine Kombinationstherapie mit Makroliden verbessert das Überleben.

taxime) elicit C. difficile germination, proliferation and high-level cytotoxin production. Mecillinam concentrations peaked at 2.7 mg/L (ribotype 001) and 3.6 mg/L (ribotype 027), .100-fold less than the MIC (.128 mg/L) for all isolates tested. Germination, proliferation and high-level ( 4 RU) cytotoxin production were not observed, indicating that induction of C. difficile proliferation and high-level cytotoxin production in the gut model may be antimicrobial-specific. Mecillinam had little effect on most enumerated bacterial groups in the gut model in agreement with in vivo studies. Bacteroides fragilis group and Bifidobacterium spp. were most numerous. Mecillinam instillation precipitated a transient decline in Bifidobacterium spp. and a gradual decline in lactose fermenters. This may be accounted for by the pharmacodynamics of the drug, which can be affected by the growth phase and bacterial inoculum density. Our results suggest that exposure of epidemic C. difficile strains to concentrations of mecillinam found in the human gut following oral dosing is not a significant risk factor for CDI induction. This may be explained by at least two factors. First, there was minimal gut microflora disruption in the presence of in vivo mecillinam concentrations and therefore little reduction in colonization resistance. While no consistent changes in bacterial genera have been correlated with simulated CDI in the gut model, a change from the predominance of obligate anaerobes (B. fragilis group and bifidobacteria) to that of facultative anaerobes was observed in previous studies where high-level cytotoxin production was observed. Mecillinam did not precipitate such changes. Second, mecillinam may not stimulate C. difficile directly. We postulated that antimicrobial concentrations may be important in determining the timing of C. difficile growth and cytotoxin production, possibly influencing C. difficile behaviour directly. Recent research indicates that antimicrobials may directly up-regulate gene expression to a greater (clindamycin and amoxicillin) or lesser (metronidazole) extent. Mecillinam may not up-regulate C. difficile gene expression. Future use of quantitative molecular technologies may help elucidate the behaviour of C. difficile exposed to antimicrobial stresses, and so help to identify bacterial groups potentially important in colonization resistance. Overall, we believe this study indicates that mecillinam likely has a low propensity to induce CDI.

Einleitung: Bei Patienten mit einer chronischen exogen allergische Alveolitis (cEAA) kann es im langjährigen Krankheitsverlauf zu einer sekundären Atempumpeninsuffizienz kommen. Die nicht-invasive Heimbeatmung (NIV) bei interstitiellen Lungenerkrankungen ist bislang nicht etabliert. Wir berichten über erste Erfahrungen bei vier Patienten mit cEAA und sekundären Atempumpeninsuffizienz bei denen eine NIV eingeleitet wurde.