Key summary of German national guideline for adult patients with nosocomial pneumonia- Update 2024 Funding number at the Federal Joint Committee (G-BA): 01VSF22007.

PURPOSE: This executive summary of a German national guideline aims to provide the most relevant evidence-based recommendations on the diagnosis and treatment of nosocomial pneumonia. METHODS: The guideline made use of a systematic assessment and decision process using evidence to decision framework (GRADE). Recommendations were consented by an interdisciplinary panel. Evidence analysis and interpretation was supported by the German innovation fund providing extensive literature searches and (meta-) analyses by an independent methodologist. For this executive summary, selected key recommendations are presented including the quality of evidence and rationale for the level of recommendation. RESULTS: The original guideline contains 26 recommendations for the diagnosis and treatment of adults with nosocomial pneumonia, thirteen of which are based on systematic review and/or meta-analysis, while the other 13 represent consensus expert opinion. For this key summary, we present 11 most relevant for everyday clinical practice key recommendations with evidence overview and rationale, of which two are expert consensus and 9 evidence-based (4 strong, 5 weak and 2 open recommendations). For the management of nosocomial pneumonia patients should be divided in those with and without risk factors for multidrug-resistant pathogens and/or Pseudomonas aeruginosa. Bacterial multiplex-polymerase chain reaction (PCR) should not be used routinely. Bronchoscopic diagnosis is not considered superior to´non-bronchoscopic sampling in terms of main outcomes. Only patients with septic shock and the presence of an additional risk factor for multidrug-resistant pathogens (MDRP) should receive empiric combination therapy. In clinically stabilized patients, antibiotic therapy should be de-escalated and focused. In critically ill patients, prolonged application of suitable beta-lactam antibiotics should be preferred. Therapy duration is suggested for 7-8 days. Procalcitonin (PCT) based algorithm might be used to shorten the duration of antibiotic treatment. Patients on the intensive care unit (ICU) are at risk for invasive pulmonary aspergillosis (IPA). Diagnostics for Aspergillus should be performed with an antigen test from bronchial lavage fluid. CONCLUSION: The current guideline focuses on German epidemiology and standards of care. It should be a guide for the current treatment and management of nosocomial pneumonia in Germany.

Evaluation of treatment response with serial CT in patients with non-tuberculous mycobacterial pulmonary disease.

OBJECTIVES: In patients with non-tuberculous mycobacterial pulmonary disease (NTM-PD), the response to treatment is evaluated based on microbiological, clinical, and radiological data. However, little is known about the dynamics of CT findings. The aim of this study was to evaluate CT changes in NTM-PD in order to define radiological criteria for treatment success. METHODS: Retrospective multicenter study (Hannover, Heidelberg, Gauting). Sixty patients with NTM-PD and at least two consecutive CT scans were included. Scoring for NTM-PD was performed by evaluating variables of bronchiectasis, mucus plugging, bronchiolitis, cavities, nodules, and consolidations on an ordinal scale from 0 to 3. Differences between baseline and follow-up were calculated, and patients with/without cultural conversion were compared using the Mann-Whitney U-test. For paired comparison of the two consecutive CT scans the Wilcoxon test was used. RESULTS: Comparing patients with and without culture conversion, there were significant differences in temporal changes of bronchiectasis (p < 0.001), cavities (p = 0.006), bronchiolitis (p < 0.001), consolidations (p = 0.004), and total score (p < 0.001). Nodules showed no significant differences between groups (p = 0.060). The Wilcoxon test showed significant differences between both CTs in patients with a microbiological cure for the total score (p < 0.001), cavities (p = 0.005), bronchiolitis (p < 0.001), and consolidations (p = 0.021) with a decrease after microbiological cure, whereas bronchiectasis (p = 0.102) and nodules (p = 0.18) stayed stable. In the case of persistently positive cultures, there was an increase in the total score (p = 0.010) which was attributable to progressive bronchiectasis (p < 0.001). CONCLUSION: Cavities, consolidations, and bronchiolitis are useful to assess treatment response, whereas bronchiectasis and nodules may remain stable despite successful treatment. CLINICAL RELEVANCE STATEMENT: Cavities, consolidations, and bronchiolitis can assess treatment response whereas bronchiectasis and nodules may remain stable despite successful treatment. In persistently positive cultures, bronchiectasis showed an increase over time indicating that NTM-PD is a progressive chronic disease. KEY POINTS: Little is known about CT changes in nontuberculous mycobacteria pulmonary disease (NTM-PD) and criteria to evaluate treatment response. In the case of culture conversion, cavities and bronchiolitis decreased whereas bronchiectasis and nodules remained stable. Cavities and bronchiolitis can evaluate treatment response in NTM, but bronchiectasis and nodules may persist despite successful treatment.

Primary Ciliary Dyskinesia in Adult Bronchiectasis: Data from the German Bronchiectasis Registry PROGNOSIS.

BACKGROUND: Primary ciliary dyskinesia (PCD) is a rare genetic disorder caused by the malfunction of motile cilia and a specific etiology of adult bronchiectasis of unknown prevalence. A better understanding of the clinical phenotype of adults with PCD is needed to identify individuals for referral to diagnostic testing. RESEARCH QUESTION: What is the frequency of PCD among adults with bronchiectasis; how do people with PCD differ from those with other etiologies; and which clinical characteristics are independently associated with PCD? STUDY DESIGN AND METHODS: We investigated the proportion of PCD among the participants of the Prospective German Non-CF-Bronchiectasis Registry (PROGNOSIS) study; applied multiple imputation to account for missing data in 64 (FEV1), 58 (breathlessness), 26 (pulmonary exacerbations), and two patients (BMI), respectively; and identified predictive variables from baseline data using multivariate logistic regression analysis. RESULTS: We consecutively recruited 1,000 patients from 38 centers across all levels of the German health care system. Overall, PCD was the fifth most common etiology of bronchiectasis in 87 patients (9%) after idiopathic, postinfective, COPD, and asthma. People with PCD showed a distinct clinical phenotype. In multivariate regression analysis, the chance of PCD being the etiology of bronchiectasis increased with the presence of upper airway disease (chronic rhinosinusitis and/or nasal polyps; adjusted OR [aOR], 6.3; 95% CI, 3.3-11.9; P < .001), age < 53 years (aOR, 5.3; 95% CI, 2.7-10.4; P < .001), radiologic involvement of any middle and lower lobe (aOR, 3.7; 95% CI, 1.3-10.8; P = .016), duration of bronchiectasis > 15 years (aOR, 3.6; 95% CI, 1.9-6.9; P < .001), and a history of Pseudomonas aeruginosa isolation from respiratory specimen (aOR, 2.4; 95% CI, 1.3-4.5; P = .007). INTERPRETATION: Within our nationally representative cohort, PCD was a common etiology of bronchiectasis. We identified few easy-to-assess phenotypic features, which may promote awareness for PCD among adults with bronchiectasis. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov; No.: NCT02574143; URL: www. CLINICALTRIALS: gov.

Clinical Features, Diagnostics, Etiology, and Outcomes of Hospitalized Solid Organ Recipients With Community-Acquired Pneumonia: A Retrospective Cohort Analysis.

BACKGROUND: Community-acquired pneumonia (CAP) is a leading cause of morbidity and mortality worldwide. Limited evidence is available on the most effective diagnostic approaches, management strategies, and long-term outcomes for CAP in patients who have undergone solid organ transplantation. RESEARCH QUESTION: What is the acute and long-term morbidity and mortality after CAP in organ transplant recipients? STUDY DESIGN AND METHODS: We retrospectively analyzed hospitalizations for CAP in solid organ recipients at the largest German transplant center. The study included patients admitted between January 1, 2010, and May 31, 2021. The reported outcomes are in-hospital and 1-year mortality, risk of cardiovascular events during hospitalization and at 1 year, admission to the ICU, and risk of pneumonia with Pseudomonas aeruginosa. Multivariable binary logistic regression using stepwise forward selection was performed to determine predictive factors for pneumonia with P aeruginosa. RESULTS: We analyzed data from 403 hospitalizations of 333 solid organ recipients. In > 60% of cases, patients had multiple comorbidities, with cardiovascular and chronic kidney disease being the most prevalent. More than one-half of the patients required oxygen supplementation after admission. In-hospital mortality (13.2%) and the death rate at 1 year postevent (24.6%) were higher than data reported from immunocompetent patients. We also observed high rates of acute cardiovascular events and events occurring 1 year after admission. Early blood cultures and bronchoscopy in the first 24 h significantly increased the odds of establishing an etiology. In our low-resistance setting, the burden of antimicrobial resistance was driven by bacteria from chronically colonized patients, mostly lung transplant recipients. INTERPRETATION: This comprehensive analysis highlights the high morbidity associated with CAP after transplantation. It also emphasizes the need for prospective multicenter studies to guide evidence-based practices and improve outcomes for these vulnerable patients.

Respiratory Syncytial Virus-Associated Respiratory Diseases in Children and Adults.

BACKGROUND: Respiratory syncytial virus (RSV) is a common cause of lower respiratory tract infections (LRTI), particularly in neonates, infants and young children, with approximately 33 million infections worldwide each year. 1-2% of episodes lead to hospitalization. There are hardly any reliable epidemiological figures on hospital - ization in adults, whose burden of disease from RSV is probably markedly underestimated. METHODS: This review is based on publications retrieved by a selective search in PubMed, with particular attention to recommendations for the prevention of RSV infection. RESULTS: There is no approved antiviral therapy for clinical practice, but preventive strategies are increasingly becoming available. Passive immunization in infants is well tolerated and highly effective, as is the active vaccination of pregnant women to prevent severe RSV infection in young infants. The former was found to lower the frequency of severe LRTI (5/4037 in the vaccination group vs. 19/4031 individuals in the placebo group), yielding an efficacy of 75.7%; for the latter, the corresponding findings were a reduction to 19/3682 in the vaccination group vs. 62/3676 in the placebo group, or 69.4% efficacy. For the active vaccination of older adults, both a recombinant vaccine with adjuvant and a bivalent vaccine have recently been approved. These, too, are well tolerated and highly effective: the former lowered the frequency of severe LRTI to 1/12466 in the vaccination group vs. 17/12494 in the placebo group (94.1% efficacy), while the latter lowered the frequency of LRTI with 3 or more manifestations to 2/17215 in the vaccination group vs. 14/17069 in the placebo group (85.7% efficacy). CONCLUSION: The approval of new RSV-specific monoclonal antibodies and active vaccinations enables targeted prevention of RSV infection in the main population groups at risk.

Perioperative Antibiotic Prophylaxis.

BACKGROUND: Postoperative surgical site infections (SSI) account for almost 25% of all nosocomial infections in Germany and are a source of increased morbidity and mortality. METHODS: This review is based on pertinent publications retrieved by a selective search in PubMed and on national and international guidelines. RESULTS: The individual risk factors for SSI must be assessed before any surgical procedure. A body-mass index above 30 kg/m2 is associated with an unadjusted risk ratio of 1.35 [1.28; 1.41] for SSI, which rises to 3.29 [2.99; 3.62] if the patient is also immunosuppressed. The risk of SSI is also significantly higher with certain types of procedure. Perioperative antibiotic prophylaxis (PAP) is clearly indicated for operations that carry a high risk of SSI (e.g., colorectal surgery) and for those that involve the implantation of alloplastic material (e.g., hip endoprostheses). PAP can usually be administered with basic antibiotics such as cefazoline. The basic principles of PAP are that it should be given by the anesthesia team in the interval from 60 minutes preoperatively up to shortly before the incision, and that its administration should only be for a short period of time, usually as a single shot. Continuing PAP onward into the postoperative period leads to increased toxicity, bacterial superinfections, and antibiotic resistance. CONCLUSION: The evidence shows that perioperative antibiotic prophylaxis is a component of a bundle of measures that can help prevent SSI. Strict indications and adherence to the basic principles of PAP are essential for therapeutic success.

Factors influencing voriconazole plasma level in intensive care patients.

Background: In clinical routine, voriconazole plasma trough levels (Cmin) out of target range are often observed with little knowledge about predisposing influences. Objectives: To determine the distribution and influencing factors on voriconazole blood levels of patients treated on intensive- or intermediate care units (ICU/IMC). Patients and methods: Data were collected retrospectively from patients with at least one voriconazole trough plasma level on ICU/IMC (n = 153) to determine the proportion of sub-, supra- or therapeutic plasma levels. Ordinal logistic regression analysis was used to assess factors hindering patients to reach voriconazole target range. Results: Of 153 patients, only 71 (46%) reached the target range at the first therapeutic drug monitoring, whereas 66 (43%) patients experienced too-low and 16 (10%) too-high plasma levels. Ordinal logistic regression analysis identified the use of extra corporeal membrane oxygenation (ECMO), low international normalized ratio (INR) and aspartate-aminotransferase (AST) serum levels as predictors for too-low plasma levels. Conclusion: Our data highlight an association of ECMO, INR and AST levels with voriconazole plasma levels, which should be considered in the care of critically ill patients to optimize antifungal therapy with voriconazole.

Photon Counting Computed Tomography with the Radiation Dose of a Chest X-Ray: Feasibility and Diagnostic Yield.

INTRODUCTION: Photon counting (PC) detectors allow a reduction of the radiation dose in CT. Chest X-ray (CXR) is known to have a low sensitivity and specificity for detection of pneumonic infiltrates. The aims were to establish an ultra-low-dose CT (ULD-CT) protocol at a PC-CT with the radiation dose comparable to the dose of a CXR and to evaluate its clinical yield in patients with suspicion of pneumonia. METHODS: A ULD-CT protocol was established with the aim to meet the radiation dose of a CXR. In this retrospective study, all adult patients who received a ULD-CT of the chest with suspected pneumonia were included. Radiation exposure of ULD-CT and CXR was calculated. The clinical significance (new diagnosis, change of therapy, additional findings) and limitations were evaluated by a radiologist and a pulmonologist considering previous CXR and clinical data. RESULTS: Twenty-seven patients (70% male, mean age 68 years) were included. With our ULD-CT protocol, the radiation dose of a CXR could be reached (mean radiation exposure 0.11 mSv). With ULD-CT, the diagnosis changed in 11 patients (41%), there were relevant additional findings in 4 patients (15%), an infiltrate (particularly fungal infiltrate under immunosuppression) could be ruled out with certainty in 10 patients (37%), and the therapy changed in 10 patients (37%). Two patients required an additional CT with contrast medium to rule out a pulmonary embolism or pleural empyema. CONCLUSIONS: With ULD-CT, the radiation dose of a CXR could be reached while the clinical impact is higher with change in diagnosis in 41%.

Association of respiratory infections and the impact of vaccinations on cardiovascular diseases.

Influenza, pneumococcal, severe acute respiratory syndrome coronavirus 2, and respiratory syncytial virus infections are important causes of high morbidity and mortality in the elderly. Beyond the burden of infectious diseases, they are also associated with several non-infectious complications like cardiovascular events. A growing body of evidence in prospective studies and meta-analyses has shown the impact of influenza and pneumococcal vaccines on types of cardiovascular outcomes in the general population. Influenza vaccination showed a potential benefit for primary and secondary prevention of cardiovascular diseases across all ages. A reduced risk of cardiovascular events for individuals aged 65 years and older was associated with pneumococcal vaccination. Despite scientific evidence on the effectiveness, safety, and benefits of the vaccines and recommendations to vaccinate elderly patients and those with risk factors, vaccination rates remain sub-optimal in this population. Doubts about vaccine necessity or efficacy and concerns about possible adverse events in patients and physicians refer to delayed acceptance. Vaccination campaigns targeting increasing professional recommendations and public perceptions should be implemented in the coming years. The aim of this review paper is to summarize the effect of vaccination in the field of cardiovascular disease to achieve a higher vaccination rate in this patient population.

Ciliary Ultrastructure Assessed by Transmission Electron Microscopy in Adults with Bronchiectasis and Suspected Primary Ciliary Dyskinesia but Inconclusive Genotype.

Whole-exome sequencing has expedited the diagnostic work-up of primary ciliary dyskinesia (PCD), when used in addition to clinical phenotype and nasal nitric oxide. However, it reveals variants of uncertain significance (VUS) in established PCD genes or (likely) pathogenic variants in genes of uncertain significance in approximately 30% of tested individuals. We aimed to assess genotype-phenotype correlations in adults with bronchiectasis, clinical suspicion of PCD, and inconclusive whole-exome sequencing results using transmission electron microscopy (TEM) and ciliary image averaging by the PCD Detect software. We recruited 16 patients with VUS in CCDC39, CCDC40, CCDC103, DNAH5, DNAH5/CCDC40, DNAH8/HYDIN, DNAH11, and DNAI1 as well as variants in the PCD candidate genes DNAH1, DNAH7, NEK10, and NME5. We found normal ciliary ultrastructure in eight patients with VUS in CCDC39, DNAH1, DNAH7, DNAH8/HYDIN, DNAH11, and DNAI1. In six patients with VUS in CCDC40, CCDC103, DNAH5, and DNAI1, we identified a corresponding ultrastructural hallmark defect. In one patient with homozygous variant in NME5, we detected a central complex defect supporting clinical relevance. Using TEM as a targeted approach, we established important genotype-phenotype correlations and definite PCD in a considerable proportion of patients. Overall, the PCD Detect software proved feasible in support of TEM.

The role of vaccination in COPD: influenza, SARS-CoV-2, pneumococcus, pertussis, RSV and varicella zoster virus.

Exacerbations of COPD are associated with worsening of the airflow obstruction, hospitalisation, reduced quality of life, disease progression and death. At least 70% of COPD exacerbations are infectious in origin, with respiratory viruses identified in approximately 30% of cases. Despite long-standing recommendations to vaccinate patients with COPD, vaccination rates remain suboptimal in this population.Streptococcus pneumoniae is one of the leading morbidity and mortality causes of lower respiratory tract infections. The Food and Drug Administration recently approved pneumococcal conjugate vaccines that showed strong immunogenicity against all 20 included serotypes. Influenza is the second most common virus linked to severe acute exacerbations of COPD. The variable vaccine efficacy across virus subtypes and the impaired immune response are significant drawbacks in the influenza vaccination strategy. High-dose and adjuvant vaccines are new approaches to tackle these problems. Respiratory syncytial virus is another virus known to cause acute exacerbations of COPD. The vaccine candidate RSVPreF3 is the first authorised for the prevention of RSV in adults ≥60 years and might help to reduce acute exacerbations of COPD. The 2023 Global Initiative for Chronic Lung Disease report recommends zoster vaccination to protect against shingles for people with COPD over 50 years.

Optimal treatment of the underlying aetiology is the most effective antimicrobial stewardship for chronic respiratory disease: a lesson learned from cystic fibrosis.

AMS in chronic lung disease can be challenging. Causal treatment of treatable traits may be the most successful AMS strategy for patients with any chronic pulmonary disease and should be brought into focus. https://bit.ly/3ptrmV8.

[Antibiotic treatment of community-acquired and hospital-acquired pneumonia]. / Antibiotische Therapie der ambulant und nosokomial erworbenen Pneumonie.

Community-acquired and nosocomial bacterial pneumonia are among the most common infectious diseases in Germany. Knowledge of possible pathogens and therapeutic implications thereof are essential to be able to provide adequate, differentiated antimicrobial therapy with the appropriate drugs, form of application, dose, and duration. New diagnostics that include multiplex polymerase chain reaction, correct interpretation of the biomarker procalcitonin, and treatment of multidrug-resistant bacteria are becoming increasingly import.

Pseudomonas aeruginosa population genomics among adults with bronchiectasis across Germany.

Genome sequencing of 130 Pseudomonas aeruginosa isolates from 110 bronchiectasis patients identified a few dominant clones common in the global bacterial population and numerous rare clones infrequently seen in the environment or other human infections https://bit.ly/3lIfD2X.

Point-of-care procalcitonin testing for lower respiratory tract infection in pulmonary outpatient care has limited value.

Lower respiratory tract infections (LRTI) are frequently the reasons for patients to visit their general practitioners or lung specialists; however, physicians tend to prescribe antibiotics less frequently than necessary. A readily available biomarker could help distinguish between viral and bacterial cause of LRTI. The primary objective of our study was to determine the diagnostic accuracy of point-of-care testing (POCT) of procalcitonin (PCT) in identifying bacterial pneumonia in outpatients with LRTI. All patients aged 18 years or older with signs and symptoms of LRTI who visited a respiratory physician were included in the study and their PCT levels were measured. In 110 patients enrolled in the study, three patients (2.7%) had PCT values above the threshold of 0.25 µg/L without proven bacterial infection, in contrast to seven patients with typical radiological signs of pneumonia without elevated POCT PCT levels. The AUC for PCT for the detection of pneumonia was 0.56 (p=0.685). POCT PCT showed limited specificity and sensitivity in distinguishing pneumonia from bronchitis or exacerbation of chronic respiratory diseases. PCT is a marker of severe bacterial infections and not suitable for milder infections in outpatient care.