Calculated parenteral initial treatment of bacterial infections: Respiratory infections.

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.

Burden and risk factors of ambulatory or hospitalized CAP: A population based cohort study.

BACKGROUND: Data on incidence, risk factors and outcome of community-acquired pneumonia (CAP) including outpatients is sparse. METHODS: We conducted a cohort study on 1.837.080 adults insured by a German statutory health insurance in 2010-2011. CAP was identified via ICD-10-GM codes, ambulatory cases were validated by antibiotic prescription within 7 days. Primary outcomes were incidence, hospitalisation and 30-day all-cause mortality. Evaluated risk factors included age, sex and comorbidities. Evaluation was done by multivariate regression analysis adjusting for these factors and health care utilization. RESULTS: CAP incidence was 9.7 per 1000 person years, hospitalisation rate 46.5%, and 30-day mortality 12.9%. 30-day mortality of ambulatory cases was 5% (with 27% subsequently hospitalized for another diagnosis before death). 30-day mortality of hospitalized patients was 21.9%, but in-hospital mortality 17.2%. Risk factors for CAP included age, male sex and all evaluated comorbidities with highest risk for neurologic (OR 2.4), lung (OR 2.3) or immunosuppressive (OR 2.1) disease. Mortality risk was highest for neurologic (OR 2.3) and malignant (OR 2.0) disease. CONCLUSIONS: CAP constitutes a major burden in terms of incidence, morbidity and all-cause mortality in hospitalized and ambulatory patients. Interventions to raise awareness for disease impact also in ambulatory patients with risk factors are warranted.

MR-proADM Predicts Exercise Capacity and Survival Superior to Other Biomarkers in PH.

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 VO2peak, 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.

Management of patients with idiopathic pulmonary fibrosis in clinical practice: the INSIGHTS-IPF registry.

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.

Adult patients with nosocomial pneumonia: epidemiology, diagnosis, and treatment.

BACKGROUND: Nosocomial pneumonia is among the most common types of infection in hospitalized patients. The increasing prevalence of multi-drug resistant organisms (MDROs) in recent years points to the need for an up-to-date clinical guideline. METHODS: An interdisciplinary S3 guideline was created on the basis of a systematic literature review in the PubMed and Cochrane Library databases, with assessment and grading of the evidence according to the GRADE system. RESULTS: 9097 abstracts and 808 articles were screened in full text, and 22 recommendations were issued. It is recommended that any antimicrobial treatment should be preceded by a microbiological diagnostic evaluation with cultures of blood and respiratory samples. The diagnosis of nosocomial pneumonia should be suspected in any patient with a new or worsened pulmonary infiltrate who meets any two of the following three criteria: leucocyte count above 10,000 or below 4000/µL, temperature above 38.3°C, and/or the presence of purulent respiratory secretions. The initially calculated antimicrobial treatment should be begun without delay; it should be oriented to the locally prevailing resistance pattern, and its intensity should be a function of the risk of infection with MDROs. The initial treatment should be combination therapy if there is a high risk of MDRO infection and/or if the patient is in septic shock. In the new guideline, emphasis is laid on a strict de-escalation concept. In particular, antimicrobial treatment usually should not be continued for longer than eight days. CONCLUSION: The new guideline's recommendations are intended to encourage rational use of antibiotics, so that antimicrobial treatment will be highly effective while the unnecessary selection of multi-drug-resistant organisms will be avoided.

Exercise capacity affects quality of life in patients with pulmonary hypertension.

BACKGROUND: 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). METHODS: Sixty-three patients with invasively diagnosed PAH (n = 48) or CTEPH (n = 15) underwent a broad panel of assessments, including cardiopulmonary exercise testing (CPET), 6-minute walking distance (6-MWD), World Health Organization functional class (WHO-FC), and assessment of hemodynamics. QoL was evaluated by the 36-item Medical Outcome Study Short Form Health Survey Questionnaire (SF-36). Exercise capacity, hemodynamics, age, gender, and mental disorders (anxiety and depression) were assessed for association with QoL subscores by uni- and multivariate regression analyses. RESULTS: Exercise capacity, WHO-FC, oxygen therapy, symptoms of right heart failure, right atrial pressure, and mental disorders were significantly associated with QoL (p < 0.05). In the stepwise backward selection multivariate analysis, depression remained an independent parameter in seven of eight subscales of the SF-36. Furthermore, peak oxygen uptake (peakVO2) during CPET, 6-MWD, anxiety, long-term oxygen therapy, right heart failure, and age remained independent factors for QoL. Hemodynamic parameters at rest did not independently correlate with any domain of the SF-36 QoL subscores. CONCLUSIONS: Mental disorders, exercise capacity, long-term oxygen therapy, right heart failure, and age play important role in the quality of life in patients with PAH and CTEPH.

Management-based risk prediction in community-acquired pneumonia by scores and biomarkers.

Community-acquired pneumonia (CAP) represents a major life-threatening infection, but disease course and outcome is highly variable. Major drivers of prognosis are respiratory failure, sepsis-related organ dysfunction and unstable comorbidities. Current risk stratification tools have been primarily designed to predict mortality and identify low risk patients potentially suitable for ambulatory management. Detection of patients at high risk for clinical deterioration by current scores remains suboptimal. Therefore, management-related risk stratification tools designed to predict benefit from early intensified monitoring and treatment strategies in hospitalised CAP are advocated. An approach including early and repeatedly evaluated clinical markers of respiratory failure, sepsis-related organ dysfunction or decompensating comorbidity combined with individual definition of treatment goals is suggested. Inflammatory biomarkers can add prognostic information. New cardiovascular or stress-related biomarkers like copeptin, midregional proadrenomedullin and cortisol have been repeatedly linked with outcome and disease course in CAP and improved clinical scoring in observational studies. Thus they represent promising tools for individualised risk stratification. A major task in future CAP research will be the evaluation of their additional value in large interventional trials with control groups incorporating strict management guidance by clinical criteria.

Serum cortisol predicts death and critical disease independently of CRB-65 score in community-acquired pneumonia: a prospective observational cohort study.

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.

Prolactin and its 16-kDa N-terminal fragment: are higher in patients with precapillary pulmonary hypertension than in a healthy control group.

We sought to determine whether patients with precapillary pulmonary hypertension show elevated serum levels of prolactin (PRL) and its 16-kDa N-terminal fragment (16-kDa PRL) and whether there is any correlation to measures of prognosis.Twenty-eight patients with idiopathic pulmonary artery hypertension, 15 with peripheral chronic thromboembolic pulmonary hypertension, and 4 with portopulmonary hypertension Child-Pugh class A were included. Our control subjects were 56 blood donors. Total prolactin was measured with an immunoluminometric assay. Antibodies against epitope C detected only the intact prolactin before it was split. The 16-kDa PRL was calculated from the difference between total and intact prolactin.Prolactin was significantly (P=0.009) higher in the study group (median, 190 mU/L; interquartile range, 162 mU/L) than in the control group (median, 140 mU/L; interquartile range, 91 mU/L). The 16-kDa PRL was significantly elevated in the study group (P=0.046). Prolactin and 16-kDa PRL correlated inversely with the 6-minute-walk distance (P <0.01) and with peak oxygen uptake during exercise (P <0.005).Serum levels of prolactin and 16-kDa PRL were significantly higher in patients with precapillary pulmonary hypertension and were inversely correlated with 6-minute-walk distance and peak oxygen uptake.These results indicate that prolactin and 16-kDa PRL might play a role in the pathophysiology of precapillary pulmonary hypertension.

Farmer's lung in a case after bullectomy.

We present a case of farmer's lung (FL) with the primary presenting feature of a large bulla in the lung. A 70-year-old nonsmoking woman with dyspnea on exercise was referred for surgical resection of a large bulla in the lung. The postoperative evaluation of the lung tissue revealed a follicular lymphocytic alveolitis and loosely formed granulomas suspicious for hypersensitivity pneumonitis (HP). The patient had worked in farming since her youth. Dyspnea on exercise was the only symptom, but it was related to the large bulla. No other radiologic features of HP were shown in a high-resolution CT of the lung. Specific IgG antibodies against typical antigens of FL were detected, bronchoalveolar lavage demonstrated no lymphocytic alveolitis but an inhalative challenge with own hay was positive. A diagnosis of chronic FL was made. Despite lung emphysema being a possible reaction in FL, giant bullae as primary and single manifestation of this disease have not been reported before.

Pulmonary hypertension in chronic hypersensitivity pneumonitis.

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).

Forceps biopsy and suction catheter for sampling in pulmonary nodules and infiltrates.

Transbronchial lung biopsy with forceps is a standard procedure in bronchoscopic tissue sampling. Suction catheter aspiration is another technique, but it is not widely known and almost no data exist regarding its diagnostic efficiency. 272 patients were included in a prospective and randomised study between February 2007 and October 2009. All were referred for bronchoscopic evaluation of pulmonary nodules/masses or infiltrates. We compared the diagnostic yield of forceps biopsy and suction catheter aspiration for a definite diagnosis and looked at whether such a diagnosis depends on the underlying pulmonary change. All patients underwent bronchoscopy with forceps biopsy and catheter aspiration. A definitive diagnosis was reached in a total of 183 (67.3%) patients, with catheter aspiration in 140 (51.5%) patients and with forceps biopsy in 136 (50.0%) patients. In 90 (33.1%) patients, a definite diagnosis could only be reached with the combination of both techniques. The diagnostic yield of forceps biopsy was better than catheter aspiration in infiltrates (p = 0.027), but was no different in nodules or masses (p = 0.09). Suction catheter aspiration is a useful technique of bronchoscopic tissue sampling. The combination of catheter aspiration and forceps biopsy results in a higher diagnostic yield than either method used alone.

Pneumomediastinum as a primary manifestation of chronic hypersensitivity pneumonitis.

BACKGROUND: Patients with chronic hypersensitivity pneumonitis (HP) can present with an insidious onset of their disease without typical fluctuating flu-like symptoms, and there are only signs of chronic respiratory failure caused by the progressive fibrotic lung disease. CASE REPORT: A 45-year-old man with a pneumomediastinum and interstitial lung disease was referred for further investigations and therapy. No traumatic event or interventional procedure had occurred prior to referral. The patient had been working in farming for almost 20 years and was exposed in childhood by his father to pigeon breeding from childhood until 20 years ago. He reported dyspnea on exercise for the previous 2 years. High-resolution CT of the lung showed a pneumomediastinum and a fibrotic interstitial lung disease without dominating ground-glass opacities. Specific IgG antibodies were markedly elevated against molds and avian antigens. Bronchoalveolar lavage demonstrated a slightly lymphocytic and neutrophilic alveolitis. After recovering from the pneumomediastinum, an open lung biopsy was performed and a UIP-pattern was detected. An inhalative challenge with hay from the work-place was positive. A diagnosis of chronic farmer's lung was made. CONCLUSIONS: Pneumomediastinum has been described in other fibrotic lung diseases, but until now it has not been described as a primary manifestation of chronic fibrotic HP. Particularly in cases of concurrent antigen sources, an inhalative challenge could be done, even in a chronic course of HP.

Antigen-specific IgG antibodies in feather duvet lung.

BACKGROUND: Feather duvet lung (FDL) is a rare subgroup of bird fancier's lung (BFL). We were interested in determining antigen-specific IgG antibodies in patients with FDL and comparing them with those with BFL. MATERIAL AND METHODS: Specific IgG antibodies against goose and duck feathers, analysed with an automated fluorimetric enzyme immunoassay, were measured in healthy subjects (group A, n = 30), in patients with FDL (group B, n = 10) and with BFL (group C, n = 35); typical specific IgG antibodies of BFL in groups B and C. RESULTS: An optimal threshold value for antibodies against goose or duck feathers to differentiate patients with either BFL or FDL from healthy subjects was determined at 10.85 mg L(-1) for goose feathers and at 8.81 mg L(-1) for duck feathers, respectively. Specific IgG antibodies against goose feathers were significantly higher in group B compared with group C. A ratio of specific IgG antibodies against goose feathers and budgerigar antigens with a threshold value of 0.91 could discriminate between patients with FDL and BFL with a specificity of 97% and a sensitivity of 90%. CONCLUSIONS: We were able to demonstrate the significant difference in IgG antibodies in patients with FDL and BFL and their contribution to discriminate between these similar kinds of extrinsic allergic alveolitis.

Presenting features of feather duvet lung.

BACKGROUND: Feather duvet lung (FDL) is a rare subgroup of bird fancier's lung. It is caused by inhalation of organic dust due to goose or duck feathers in duvets or pillows. METHODS: A retrospective review of the medical records of 13 patients with FDL was performed to assess the specific history and review clinical characteristics of patients with this disease. RESULTS: All patients were female with a mean age of 53 years (26-71). They were recently exposed to feather duvets (6), pillows (1) or both (6). Specific histories were duvets or pillows filled with raw goose feathers from their own farms (4), intensive contact with goose feathers in youth (3), and bird exposure prior to symptom onset (5). In all patients specific IgG antibodies to goose and/or duck feathers were detected. Pulmonary function tests revealed a moderate to severe reduced diffusion capacity and a mild restrictive pattern. High-resolution computed tomography was performed in 11 patients and demonstrated predominantly ground-glass opacities (10) and fibrosis (6). In bronchoalveolar lavage fluid, lymphocytic alveolitis was demonstrated in all patients. Lung biopsies were obtained in 9 patients and demonstrated lymphocytic alveolitis (8), granulomas (3), bronchiolitis obliterans organizing pneumonia pattern (2), and usual interstitial pneumonia pattern (1). CONCLUSIONS: The clinical findings of FDL are typical of extrinsic allergic alveolitis. Primary sensitization could be due to former exposure to bird antigens at home or goose/duck feather exposure in youth. In view of the increasing popularity of feather duvets, FDL should be considered in the differential diagnosis of patients with extrinsic allergic alveolitis.

Acute effects of NPPV in interstitial lung disease with chronic hypercapnic respiratory failure.

OBJECTIVE: A case series evaluating the acute effects of noninvasive positive pressure ventilation (NPPV) in patients with chronic hypercapnic respiratory failure (HRF) secondary to interstitial lung diseases (ILD). PATIENTS AND METHODS: Ten patients with ILD were retrospectively evaluated. All had restrictive lung function (mean TLC, 47.6+/-12.6% predicted) and chronic hypercapnic respiratory failure (mean pH=7.39+/-0.02). Arterial blood gas analysis and lung function were compared before and after the application of controlled pressure-limited NPPV. RESULTS: Daytime PaCO(2) during spontaneous breathing decreased by 5.4+/-1.3mmHg (95% confidence interval, 4.5-6.3), from 57.7+/-5.1mmHg to 52.3+/-5.9 (p<0.001); while daytime PaO(2) increased by 3.4+/-3.3mmHg (95% confidence interval, 1.0-5.8), from 63.7+/-3.5mmHg to 67.1+/-3.4 (p=0.01); and TLC increased by 3.9+/-4.5% (95% confidence interval, 0.7-7.1), from 47.6+/-12.6%mmHg to 51.5+/-10.0% (p=0.023). CONCLUSIONS: In patients with ILD and chronic HRF controlled NPPV is tolerated and can acutely improve blood gas levels. Further studies examining the long-term benefits need to be explored.

Early recurrence of Pneumocystis jiroveci pneumonia in two HIV-infected patients: linking infection relapse and immune reconstitution syndrome.

This case report describes two HIV-positive patients with Pneumocystis jiroveci pneumonia who relapsed within 1 week of starting secondary prophylaxis and antiretroviral treatment. Diagnostic and therapeutic approaches as well as the need to establish risk factors for infection recurrence or early immune reconstitution syndrome are highlighted.

[Decision guidance for antibiotic treatment of acute exacerbation of COPD]. / Akute Exazerbation der COPD. Wann sind Antibiotika sinnvoll?

The evidential support for antimicrobial therapy of AECB is very limited. Hence, the indication for antibiotic treatment for AECB should be made very discriminatingly. For outpatients, the criteria for the indication are met when COPD is moderate to severe and all three symptoms for an exacerbation are present (increased sputum production, increased sputum purulence and increased dyspnoea), when exacerbations recur frequently or when there is cardiac comorbidity. The choice of the antibiotic is based on the severity of the COPD, the expected frequency of recurrence, risk factors for treatment failure, a recent antibiotic therapy and microbiological evidence of pathological organisms.

Monotherapy versus Combination Therapy in Patients Hospitalized with Community-Acquired Pneumonia.

Current international guidelines for the management of community acquired pneumonia (CAP) recommend therapy with a beta-lactam plus a macrolide or a 'respiratory' fluoroquinolone alone in patients hospitalized in a medical ward, and combination therapy with a beta-lactam plus a macrolide or a fluoroquinolone in patients hospitalized in the intensive care unit. However, which of the available options should be preferred remains a matter of debate, and there are surprisingly few prospective randomized trials strictly comparing mono- versus dual therapy strategies in CAP patients. Thus, the recommendation of combining a macrolide with a beta-lactam rather than using a beta-lactam alone in hospitalized patients is derived mainly from observational data, and the suggested combination of a beta-lactam with a fluoroquinolone in severe CAP has been rarely examined in a clinical trial.As there have been sound theoretical arguments for and against combination therapy regimens, the rationale for the different options is discussed and available clinical trial data are reviewed in this article. A final conclusion about the superiority of one antibacterial regimen over another in hospitalized patients with CAP cannot be drawn on the basis of the limited data available. So far, combination therapy probably should be preferred in all patients presenting with severe pneumonia, whereas in general, combination therapy is not necessary in patients in a medical ward, and combination therapy with a beta-lactam plus a macrolide or monotherapy with a respiratory fluoroquinolone should be considered equivalent in this latter patient group. On the other hand, the available data demonstrate that empirical coverage of atypical bacteria in all patients with mild-to-moderate CAP seems unnecessary, and beta-lactam monotherapy might perform equally well when compared with respiratory fluoroquinolones in patients with non-severe CAP. Thus, the alternative use of a beta-lactam alone at adequate dosage in clinically stable patients seems justified, if CAP due to Legionella pneumophila is unlikely.