Chronic inhaled antibiotic therapy in people with cystic fibrosis with Pseudomonas aeruginosa infection in Germany.

BACKGROUND: Several clinical guidelines recommend chronic inhaled therapy for pwCF (people with cystic fibrosis) and chronic Pseudomonas aeruginosa infection of the lungs. METHODS: To demonstrate what kind of therapy regimens are used in Germany, we retrospectively analysed chronic inhaled antibiotic therapy within the cohort of the German CF Registry in 2020. For comparison we also analysed the use of inhaled antibiotics in pwCF with intermittent Pseudomonas or without Pseudomonas infection. RESULTS: A total of 1960 pwCF had chronic P. aeruginosa infection and were retrospectively evaluated. Almost 90% (n = 1751) received at least one inhaled antibiotic. The most commonly used inhaled antibiotic was colistin solution for inhalation (55.2%), followed by aztreonam solution for inhalation (32.6%) and tobramycin solution for Inhalation (30%). Almost 56% of adults and 44% of children alternated two antibiotics for inhalation. In children, alternating colistin + tobramycin was the most often used regimen. In adults, only 23% used colistin + tobramycin; there was a wide range of treatment regimens among adults using two inhaled antibiotics alternately. 2456 pwCF had no Pseudomonas infection, but almost 24% had a chronic inhaled antibiotic therapy, while 56% of 361 pwCF and intermittent chronic Pseudomonas infection had a chronic inhaled antibiotic therapy. CONCLUSION: In all three groups the most commonly used inhaled antibiotic was colistin solution for inhalation. Almost 56% of adults and 44% of children with chronic Pseudomonas infection alternated two antibiotics for inhalation. It will be interesting to see how the introduction of the highly effective modulator elexacaftor/tezacaftor/ivacaftor will change the use of inhaled antibiotics.

[Complications after Indwelling Pleural Catheter Implant for Symptomatic Recurrent Benign and Malignant Pleural Effusions]. / Komplikationen nach pleuralem getunnelten Dauerkatheter bei symptomatischen rezidivierenden benignen und malignen Pleuraergüssen.

BACKGROUND: Implant of indwelling pleural catheters (IPC) represents an established therapy method in addition to pleurodesis for symptomatic recurrent benign and malignant pleural effusions (BPE and MPE).There are only few studies on IPC safety during follow-up, especially with regard to infection and pneumothorax rates.The aim of our investigation was to determine the complication frequency after IPC implant and its predictive factors in patients with BPE vs. MPE. METHODS: Retrospective analysis of all IPC implantations in the pneumology department at the University Hospital Dresden during 2015 - 2018. RESULTS: An IPC was implanted in 86 patients (43 m/f each; age 66.9 ±â€Š13.3 years) with symptomatic BPE and MPE. BPE and MPE was present in 12.8 % (11/86) and 87.2 % (75/86) of the patients, respectively.A predominantly small and asymptomatic pneumothorax was detectable as an immediate complication in 43/86 (50 %) of patients; 34/43 (79 %) of patients did not require any specific therapy. For 9/43 patients, IPC suction was required for a median period of three days; 8/43 patients had a large pneumothorax with partial or complete regression after a median period of two days.Catheter infection developed in 15.1 % (13/86) of the total group and 36.4 % (4/11) of the BPE vs. 12 % (9/75) of the MPE after a median period of 87 (BPE/MPE 116/87) days. This was more common in BPE (p = 0.035), large pneumothorax (4/8 patients; p = 0.015) and longer catheter dwell times (124 ±â€Š112 vs. 71 ±â€Š112 days; p = 0.07). CONCLUSION: Small pneumothoraxes are frequent after IPC implantation, but usually do not require specific therapy. IPC infection was detected in 15.1 % of all patients after a median period of 87 days. This was more common in patients with BPE, longer catheter dwell times and large pneumothorax.

[CF Lung Disease - a German S3 Guideline: Module 2: Diagnostics and Treatment in Chronic Infection with Pseudomonas aeruginosa]. / S3-Leitlinie: Lungenerkrankung bei Mukoviszidose ­ Modul 2: Diagnostik und Therapie bei der chronischen Infektion mit Pseudomonas aeruginosa.

Cystic Fibrosis (CF) is the most common autosomal-recessive genetic disease affecting approximately 8000 people in Germany. The disease is caused by mutations in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene leading to dysfunction of CFTR, a transmembrane chloride channel. This defect causes insufficient hydration of the epithelial lining fluid which leads to chronic inflammation of the airways. Recurrent infections of the airways as well as pulmonary exacerbations aggravate chronic inflammation, lead to pulmonary fibrosis and tissue destruction up to global respiratory insufficiency, which is responsible for the mortality in over 90 % of patients. The main aim of pulmonary treatment in CF is to reduce pulmonary inflammation and chronic infection. Pseudomonas aeruginosa (Pa) is the most relevant pathogen in the course of CF lung disease. Colonization and chronic infection are leading to additional loss of pulmonary function. There are many possibilities to treat Pa-infection. This is a S3-clinical guideline which implements a definition for chronic Pa-infection and demonstrates evidence-based diagnostic methods and medical treatment for Pa-infection in order to give guidance for individual treatment options.

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.

Admission lactate predicts poor prognosis independently of the CRB/CURB-65 scores in community-acquired pneumonia.

OBJECTIVES: Community-acquired pneumonia (CAP) is associated with a high risk of respiratory failure or septic organ dysfunction. Lactate is an established early marker of prognosis and sepsis severity, but few data exist in patients with CAP. METHODS: We performed a retrospective cohort study of consecutive adult CAP patients without treatment restrictions or direct intensive care unit admission. Lactate was measured as a point-of-care test within the capillary admission blood gas analysis, and its prognostic value was compared to the CRB/CURB-65 criteria by multivariate and receiver operating characteristic (ROC) curve analysis. The primary endpoint was the combination of need for mechanical ventilation, vasopressors, intensive care unit admission or hospital mortality. RESULTS: Of 303 included patients, 75 (25%) met the primary endpoint. After ROC analysis, lactate predicted the primary endpoint (area under the curve 0.67) with an optimal cutoff of >1.8 mmol/L. Of the 76 patients with lactate above this threshold, 35 (46%) met the primary endpoint. After multivariate analysis, the predictive value of lactate was independent of the CRB/CURB-65 scores. The addition of lactate >1.8 mmol/L to the CRB/CURB-65 scores resulted in significantly improved area under the curves (0.69 to 0.74, p 0.005 and 0.71 to 0.75, p 0.008 respectively). Fourteen (42%) of 33 and 11 (39%) of 28 patients meeting the endpoint despite presenting with 0 or 1 CRB/CURB-65 criteria had lactate >1.8 mmol/L. CONCLUSIONS: Admission lactate levels significantly improved the prognostic value of the CRB/CURB-65 scores in CAP patients. Lactate may therefore be considered a rapid, cheap and broadly available additional criterion for the assessment of risk in patients with CAP.

Copeptin predicts clinical deterioration and persistent instability in community-acquired pneumonia.

RATIONALE: Optimal risk prediction of early clinical deterioration in community-acquired pneumonia (CAP) remains unresolved. We prospectively examined the predictive value of the new biomarkers copeptin and proadrenomedullin (MR-proADM) in comparison to clinical scores and inflammatory markers to predict early high risk prognosis in CAP. METHODS: 51 consecutive hospitalised adult patients were enrolled. We measured CRB-65- and PSI-scores, the ATS/IDSA 2007 minor criteria to predict ICU-admission and the biomarkers CRP, procalcitonin, copeptin and MR-proADM on admission. Predefined outcome parameters were combined mortality or ICU-admission after 7 days and clinical instability after 72 h. RESULTS: Copeptin was the only biomarker significantly elevated in patients with either adverse short term outcome (p = 0.003). According to ROC-curve analysis, copeptin predicted ICU admission or death within 7 days (AUC 0.81, cut-off 35 pmol/l: sensitivity 78%, specificity 79%) and persistent clinical instability after 72 h (AUC 0.74). In Kaplan-Meier-analysis patients with high copeptin showed lower ICU-free survival within 7 days (p = 0.001). The diagnostic accuracy of copeptin was superior to the CRB-65 score and comparable to the PSI-score and the ATS/IDSA minor criteria. If copeptin was included as additional minor criterion for combined 7-day mortality or ICU-admission, the diagnostic accuracy of the minor criteria was significantly improved (p = 0.045). CONCLUSION: Copeptin predicts early deterioration and persistent clinical instability in hospitalised CAP and improves the predictive properties of existing clinical scores. It should be evaluated within a biomarker guided strategy for early identification of high risk CAP patients who most likely benefit from early intensified management strategies.