[Epidemiology, Diagnosis and Treatment of Adult Patients with Nosocomial Pneumonia - Update 2017 - S3 Guideline of the German Society for Anaesthesiology and Intensive Care Medicine, the German Society for Infectious Diseases, the German Society for Hygiene and Microbiology, the German Respiratory Society and the Paul-Ehrlich-Society for Chemotherapy, the German Radiological Society and the Society for Virology]. / Epidemiologie, Diagnostik und Therapie erwachsener Patienten mit nosokomialer Pneumonie ­ Update 2017.

Nosocomial pneumonia (HAP) is a frequent complication of hospital care. Most data are available on ventilator-associated pneumonia. However, infections on general wards are increasing. A central issue are infections with multidrug resistant (MDR) pathogens which are difficult to treat in the empirical setting potentially leading to inappropriate use of antimicrobial therapy.This guideline update was compiled by an interdisciplinary group on the basis of a systematic literature review. Recommendations are made according to GRADE giving guidance for the diagnosis and treatment of HAP on the basis of quality of evidence and benefit/risk ratio.This guideline has two parts. First an update on epidemiology, spectrum of pathogens and antimicrobials is provided. In the second part recommendations for the management of diagnosis and treatment are given. New recommendations with respect to imaging, diagnosis of nosocomial viral pneumonia and prolonged infusion of antibacterial drugs have been added. The statements to risk factors for infections with MDR pathogens and recommendations for monotherapy vs combination therapy have been actualised. The importance of structured deescalation concepts and limitation of treatment duration is emphasized.

Clinical Relevance of Computed Tomography Pulmonary Venography.

BACKGROUND: In clinical routine, the pulmonary contrast-enhanced chest computer tomography (CT) is usually focussed on the pulmonary arteries. The purpose of this pictorial essay is to raise the clinicians' awareness for the clinical relevance of CT pulmonary venography. CASE PRESENTATION: A pictorial case series illustrates the clinical consequences of different pulmonary venous pathologies on systemic, pulmonary and bronchial circulation. CONCLUSION: Computed tomography pulmonary venography must be considered before atrial septal defect (ASD) closure and pulmonary lobectomy. Computed tomography pulmonary venography should be considered for patients with right ventricular overload and pulmonary hypertension, as well as for patients with unclear recurrent pulmonary infections, progressive dyspnoea, pleural effusions, haemoptysis, and for patients with respiratory distress after lung-transplantation.

[Management of Adult Community-acquired Pneumonia and Prevention - Update 2016]. / Behandlung von erwachsenen Patienten mit ambulant erworbener Pneumonie und Prävention - Update 2016.

The present guideline provides a new and updated concept of treatment and prevention of adult patients with community-acquired pneumonia. It replaces the previous guideline dating from 2009.The guideline was worked out and agreed on following the standards of methodology of a S3-guideline. This includes a systematic literature search and grading, a structured discussion of recommendations supported by the literature as well as the declaration and assessment of potential conflicts of interests.The guideline has a focus on specific clinical circumstances, an update on severity assessment, and includes recommendations for an individualized selection of antimicrobial treatment as well as primary and secondary prevention.

Potential clinical predictors of outcome after postoperative radiotherapy of non-small cell lung cancer.

AIM: The aim of this analysis was to investigate the impact of tumour-, treatment- and patient-related cofactors on local control and survival after postoperative adjuvant radiotherapy in patients with non-small cell lung cancer (NSCLC), with special focus on waiting and overall treatment times. PATIENTS AND METHODS: For 100 NSCLC patients who had received postoperative radiotherapy, overall, relapse-free and metastases-free survival was retrospectively analysed using Kaplan-Meier methods. The impact of tumour-, treatment- and patient-related cofactors on treatment outcome was evaluated in uni- and multivariate Cox regression analysis. RESULTS: No statistically significant difference between the survival curves of the groups with a short versus a long time interval between surgery and radiotherapy could be shown in uni- or multivariate analysis. Multivariate analysis revealed a significant decrease in overall survival times for patients with prolonged overall radiotherapy treatment times exceeding 42 days (16 vs. 36 months) and for patients with radiation-induced pneumonitis (8 vs. 29 months). CONCLUSION: Radiation-induced pneumonitis and prolonged radiation treatment times significantly reduced overall survival after adjuvant radiotherapy in NSCLC patients. The negative impact of a longer radiotherapy treatment time could be shown for the first time in an adjuvant setting. The hypothesis of a negative impact of longer waiting times prior to commencement of adjuvant radiotherapy could not be confirmed.

Tolerated sting challenge in patients on Hymenoptera venom immunotherapy improves health-related quality of life.

BACKGROUND: Sting challenge with a live insect remains the best test for proving the efficacy of immunotherapy in Hymenoptera allergy. OBJECTIVE: We studied the impact of tolerated sting challenge on quality of life. PATIENTS AND METHODS: In this prospective study, data were collected via self-report questionnaires completed by consenting patients with Hymenoptera venom allergy on venom immunotherapy before and after a sting challenge. RESULTS: The study population comprised 100 adult patients (82 with yellow jacket allergy and 18 with honeybee allergy) who participated between September 2009 and November 2010. After the sting challenge, the score on the Vespid Allergy Quality of Life Questionnaire revealed a statistically significant improvement (mean [SD] change, 0.73 [0.98]; P < .0001; 95% CI, 0.52-0.94). This improvement was independent of the patients' gender and age and the severity of the initial anaphylactic reaction. A statistically significant improvement was documented in 2 subgroups of the Short Form 36 Health Survey (physical functioning, mean change, -5.78 [25.23]; P = .038; 95% CI, -11.22 to -0.34; vitality, mean change -4.29 [12.49]; P =.002; 95% CI, -7.02 to -1.57). CONCLUSIONS: Sting challenge results in a significant improvement in disease-specific quality of life and subgroups of general quality of life in patients allergic to Hymenoptera venom receiving established venom immunotherapy.

Tolerability to etoricoxib in patients with aspirin-exacerbated respiratory disease.

BACKGROUND: The use of selective cyclooxygenase (COX) 2 inhibitors as an alternative to aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) has been suggested for patients with aspirin-exacerbated respiratory disease (AERD). OBJECTIVE: To evaluate tolerability to etoricoxib, a second-generation COX-2 inhibitor with high in vitro selectivity for COX-2 in patients with AERD. METHODS: We conducted a retrospective review of patients with suspected aspirin intolerance seen between October 2007 and April 2012. Single-blind, placebo-controlled oral challenges with increasing doses of aspirin and etoricoxib were performed on 3 different days. RESULTS: Of 262 patients with suspected aspirin intolerance, 248 underwent challenge testing with aspirin and 122 (49.2%) showed positive test results. In 104 of these aspirin-sensitive patients, etoricoxib was tested as an alternative drug and was tolerated in all but 3 (2.9%), who developed a positive asthmatic reaction. CONCLUSIONS: The highly selective COX-2 inhibitor etoricoxib was tolerated in most but not all patients tested. An oral provocation test is therefore recommended before prescribing etoricoxib for patients with AERD.

[Informations and recommendations of the German Respiratory Society and the Paul-Ehrlich-Society for chemotherapy concerning the outbreak of influenza A(H7N9) virus infections in humans]. / Informationen und Empfehlungen der Deutschen Gesellschaft für Pneumologie und Beatmungsmedizin e.V. und der Paul-Ehrlich-Gesellschaft für Chemotherapie e.V. zum Ausbruch der Influenza A(H7N9)-Virus-Infektion beim Menschen.

In March 2013, the first cases of avian influenza virus infections in humans were reported by the authorities of the PR of China to the World Health Organization. This influenza A(H7N9) virus comprises genes of at least four different avian influenza viruses, some segments mimicking human-like influenza-signatures. Until 11 August, 2013 135 humans were infected, 44 (33%) died. The clinical course is characterized by fever, cough, gastrointestinal symptoms, lympho- and thrombopenia as well by the rapid onset of an acute respiratory distress syndrome in nearly 25% of the cases. Although human to human transmission may have occurred only in the context of three clusters, strict hygiene measures should be instituted and any suspect case should be reported to the local health authorities immediately. The detection of influenza A(H7N9) is based on real-time polymerase chain reaction (PCR). Antiviral treatment should be initiated as early as possible for suspect, probable or confirmed cases, even when 48 hours have passed after symptom onset. At present the future development of this epidemic cannot be predicted.

[Epidemiology, diagnosis and treatment of adult patients with nosocomial pneumonia. S-3 Guideline of the German Society for Anaesthesiology and Intensive Care Medicine, the German Society for Infectious Diseases, the German Society for Hygiene and Microbiology, the German Respiratory Society and the Paul-Ehrlich-Society for Chemotherapy]. / Epidemiologie, Diagnostik und Therapie erwachsener Patienten mit nosokomialer Pneumonie. S-3 Leitlinie der Deutschen Gesellschaft für Anästhesiologie und Intensivmedizin e.V., der Deutschen Gesellschaft für Infektiologie e.V., der Deutschen Gesellschaft für Hygiene und Mikrobiologie e.V., der Deutschen Gesellschaft für Pneumologie und Beatmungsmedizin e.V. und der Paul-Ehrlich-Gesellschaft für Chemotherapie e.V.

Nosocomial pneumonia (HAP) is a frequent complication of hospital care. Most data are available on ventilator-associated pneumonia. However infections on general wards are also increasing. A central issue are infections with multi drug resistant (MDR) pathogens which are difficult to treat particularly in the empirical setting potentially leading to inappropriate use of antimicrobial therapy. This guideline was compiled by an interdisciplinary group on the basis of a systematic literature review. Recommendations are made according to GRADE giving guidance for the diagnosis and therapy of HAP on the basis of quality of evidence and benefit/risk ratio. The guideline has two parts. First an update on epidemiology, spectrum of pathogens and antiinfectives is provided. In the second part recommendations for the management of diagnosis and treatment are given. Proper microbiologic work up is emphasized for knowledge of the local patterns of microbiology and drug susceptibility. Moreover this is the optimal basis for deescalation in the individual patient. The intensity of antimicrobial therapy is guided by the risk of infections with MDR. Structured deescalation concepts and strict limitation of treatment duration should lead to reduced selection pressure.

Ambrisentan improves exercise capacity and symptoms in patients with portopulmonary hypertension.

INTRODUCTION: Ambrisentan, a selective endothelin receptor antagonist has been approved in several countries for pulmonary arterial hypertension. No data have been published on the efficacy of ambrisentan on improvement of exercise capacity in patients with portopulmonary hypertension (PoPH). PATIENTS AND METHODS: We retrospectively analyzed the safety and efficacy of ambrisentan in patients with PoPH in four German university hospitals. RESULTS: 14 patients with moderate to severe PoPH were included. The median follow-up was 16 months (IQR, 12 - 21). 6 minute walk tests after 6 and 12 months improved from 376 meters (IQR, 207 - 440) at baseline to 415 meters (IQR, 393 - 475; p = 0.011) and 413 meters (IQR, 362 - 473, p = 0.005), respectively. WHO- functional class after 1 year of therapy with ambrisentan also improved significantly (p = 0.014). No significant changes in blood gas analysis and liver function tests (aspartate aminotransferase, alanine aminotransferase, total bilirubin, and international normalized ratio) during therapy with ambrisentan were detectable. CONCLUSIONS: The present study demonstrates significant improvement of exercise capacity and clinical symptoms without relevant safety concerns during ambrisentan treatment in patients with PoPH.

Adrenal function is related to prognosis in moderate community-acquired pneumonia.

The aim of our study was to prospectively examine adrenal function, including cosyntropin stimulation, and its prognostic value in patients with moderate community-acquired pneumonia (CAP). 59 consecutive adult patients hospitalised on normal wards because of CAP were enrolled. A cosyntropin stimulation test was performed and serum concentrations of C-reactive protein, procalcitonin, interleukin-6, tumour necrosis factor-α, ACTH, cortisol, dehydroepiandrosterone (DHEA) and dehydroepiandrosterone-sulfate (DHEAS) were measured. Predefined outcome parameters were clinical instability after 72 h, mortality and combined intensive care unit (ICU) admission or mortality. Critical illness-related corticosteroid insufficiency (CIRCI) occurred in six patients (10.3%). Cortisol, age-corrected DHEA, ACTH and the DHEA/DHEAS ratio were elevated in patients remaining unstable after 72 h. In multivariate analysis, cortisol (p = 0.03), ACTH (p = 0.04) and the pneumonia severity index (PSI) score (p = 0.005) independently predicted clinical instability after 72 h, and only cortisol predicted mortality (p = 0.04) and combined ICU-admission or mortality (p = 0.006). The predictive value of serum cortisol after receiver operating characteristic curve analysis equalled that of the PSI score. Patients with serum cortisol >734 nmol·L(-1) had a high probability for mortality (OR 38.3; p = 0.002). CIRCI is rare in patients with moderate CAP. Adrenal function is related to the prognosis of CAP. The diagnostic accuracy of serum cortisol equals that of the PSI score. Serum cortisol should be evaluated within clinical prediction scores on larger studies.

[Retrospective analysis of tuberculosis caused by Mycobacterium bovis 2004 - 2008]. / Retrospektive Analyse von Tuberkuloseerkrankungen durch Mycobacterium bovis 2004 - 2008.

BACKGROUND: mycobacterium bovis is a rare cause of tuberculosis in Germany. Epidemiological data are sparse. METHODS: we have carried out a retrospective analysis of all patients diagnosed with tuberculosis caused by M. BOVIS in a pneumological referral centre between 2004 and 2008. RESULTS: M. bovis was isolated in 8 out of 203 (3,9  %) patients with a new diagnosis of tuberculosis. The median age of these patients was 69 years, and 7 out of 8 showed risk factors for reactivation of a latent tuberculosis infection. In 4 patients (50  %) an extrapulmonary manifestation was present. All isolates of M. bovis were resistant to pyrazinamide, one isolate had an additional resistance to isoniazide. In 6 out of 8 patients prolonged tuberculostatic treatment of 8 - 12 months was recommended. CONCLUSIONS: the proportion of tuberculosis caused by M. bovis was higher than that reported for Germany (3.9 vs. 1,5 %). Predominantly elderly patients with risk factors for reactivation of a latent tuberculosis infection were affected. In accordance with the literature a high rate of extrapulmonary manifestations was detected. Because of the genetic resistance of M. bovis to pyrazinamide prolonged antimycobacterial treatment is recommended.

[Current concepts for the microbiological detection of airway pathogens]. / Aktuelle Konzepte zum mikrobiologischen Nachweis von Atemwegserregern.

The frequency and range of bacterial pathogens in respiratory tract infections depends on a variety of variables. The aetiology is influenced by the type of respiratory tract infection (acute bronchitis, acute exacerbation of chronic bronchitis, community-acquired pneumonia, nosocomial pneumonia), geographic and seasonal factors, and by the diagnostic methods implemented to identify the pathogens. Furthermore, there exists a considerable uncertainty concerning the clinical relevance of positive bacteriological findings in respiratory secretions because they are retrieved from non-sterile or contaminated environments. To differentiate infection from contamination, both microbiological and clinical findings have to be assessed, which might be difficult in the setting of systemic or local immunosuppression.

Hypersensitivity pneumonitis associated with the use of temozolomide.

The aim of the present study was to investigate a case of hypersensitivity pneumonitis associated with the use of temozolomide in the treatment of gliosarcoma. A 54-yr-old female developed dyspnoea, cough and hypoxia after surgical resection for gliosarcoma and adjuvant radio- and chemotherapy with temozolomide. A high-resolution computed tomography scan of the thorax showed a bilateral ground-glass pattern. Bronchoscopy with bronchoalveolar lavage and lung biopsies was performed. Bronchoalveolar lavage demonstrated significant lymphocytic alveolitis and transbronchial lung biopsies revealed lymphocytic infiltration with foamy macrophages, consistent with hypersensitivity pneumonitis. There was no evidence of other causes, including infections. After withdrawing temozolomide and initiating prednisolone therapy, the patient had no further pulmonary symptoms. To the present authors' knowledge, this is the first definitively described case of temozolomide-associated hypersensitivity pneumonitis.

Net reclassification improvement with serial biomarkers and bed-sided spirometry to early predict the need of organ support during the early post-transplantation in-hospital stay in allogeneic HCT recipients.

To predict the need of intensive care unit admission with organ support during the transplantation hospital stay in 101 consecutives allogeneic hematopoietic cell transplantation (allo-HCT) recipients the added predictive utility of three times per week Copeptin, MR-proADM, MR-proANP, NT-proBNP, IL-6, Procalcitonin, D-dimer and three times per week bed-sided pulmonary function test was determined in comparison with an index model. The index model was calculated by multivariate regression analysis out of the patients' routine laboratory parameters. To calculate the added predictive utility of the investigated markers the Δ-AUC and the continuous net reclassification improvement (cNRI + 2 to - 2), splitted for events and non-events were calculated for each marker in comparison with the index model. According to the Δ-AUC, none of the parameters improved risk prediction. In contrast, the cNRI was significantly improved for events and non-events by Copeptin (event 0.75, p value 0.0013; non-event 0.4, p value 0.000079) and for events by NT-proBNP (0.6, p value 0.018). D-dimer and PCT significantly predicted the non-event. Of the spirometry parameters, the FEF50% improved prediction of event and non-event according to the cNRI model. Our data support the additional serial analysis of Copeptin and NT-proBNP in allo-HCT recipients during the transplantation hospital stay.

Ciprofloxacin intravenous dose variance.

Following different intravenous dosages of ciprofloxacin in volunteers, only limited variation in serum concentrations have been reported using volunteers in both single- and multiple-dose studies. In patients, a greater variability in serum concentrations was reported during intravenous ciprofloxacin treatment. This was also the case in patients with varying degrees of renal insufficiency. However, no report exists of nonmeasurable ciprofloxacin serum concentrations during intravenous treatment in patients.

Unique aspects of quinolone pharmacokinetics.

Despite some limited differences in pharmacokinetic parameters among the newer quinolones, their pharmacology is characterised by high volumes of distribution, long elimination half-lives, good to excellent bioavailability, low protein binding, limited biotransformation and different elimination pathways (mainly through the kidneys). The unique aspects of quinolones in comparison with beta-lactams and aminoglycosides are their higher volumes of distribution, longer elimination half-lives and their intracellular high concentration, especially in phagocytic cells.

Comparative pharmacokinetics of new quinolones.

The pharmacokinetic properties of the new quinolones are characterised by a high volume of distribution, long biological half-life, low serum protein binding, elimination mainly by the kidneys, high total and renal clearances, limited biotransformation and a moderate to excellent bioavailability after oral administration. However, each quinolone derivative (ciprofloxacin, enoxacin, norfloxacin, ofloxacin and pefloxacin) possesses individual pharmacokinetic characteristics, which should be considered in the treatment of patients, especially when liver and/or renal dysfunction exists.

Systemic and endotracheal antibiotic prophylaxis of nosocomial pneumonia in ICU.

Nosocomial pneumonias, especially in ventilated patients, are a continuing problem in modern medicine. Pathogens most commonly involved with these pneumonias are Enterobacteriaceae, Ps. aeruginosa and S. aureus. Several prevention measures for nosocomial pneumonia are possible such as parenteral and topical antibiotics--a very controversial issue. Several studies with parenteral antibiotics, starting as early as 1954, could not prove any benefit of parenteral antibiotics in pneumonia prevention. Topical antibiotics, starting with polymyxin or gentamicin via the endotracheal tube in the 70s, gave controversial results. In a prospective, randomized, double-blind placebo controlled study with gentamicin via the endotracheal tube in ventilated ICU patients we found no significant reduction of pneumonia rate and mortality. However, the combined approach (SDD) of oropharyngeal, gastrointestinal and parenteral use of certain antibiotics appears to give promising results in specific patient subgroups such as ventilated polytrauma patients in ICU.