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%.

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.

C-reactive protein and procalcitonin for antimicrobial stewardship in COVID-19.

PURPOSE: Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory coronavirus 2 (SARS-CoV-2) has spread around the world. Differentiation between pure viral COVID-19 pneumonia and secondary infection can be challenging. In patients with elevated C-reactive protein (CRP) on admission physicians often decide to prescribe antibiotic therapy. However, overuse of anti-infective therapy in the pandemic should be avoided to prevent increasing antimicrobial resistance. Procalcitonin (PCT) and CRP have proven useful in other lower respiratory tract infections and might help to differentiate between pure viral or secondary infection. METHODS: We performed a retrospective study of patients admitted with COVID-19 between 6th March and 30th October 2020. Patient background, clinical course, laboratory findings with focus on PCT and CRP levels and microbiology results were evaluated. Patients with and without secondary bacterial infection in relation to PCT and CRP were compared. Using receiver operating characteristic (ROC) analysis, the best discriminating cut-off value of PCT and CRP with the corresponding sensitivity and specificity was calculated. RESULTS: Out of 99 inpatients (52 ICU, 47 Non-ICU) with COVID-19, 32 (32%) presented with secondary bacterial infection during hospitalization. Patients with secondary bacterial infection had higher PCT (0.4 versus 0.1 ng/mL; p = 0.016) and CRP (131 versus 73 mg/L; p = 0.001) levels at admission and during the hospital stay (2.9 versus 0.1 ng/mL; p < 0.001 resp. 293 versus 94 mg/L; p < 0.001). The majority of patients on general ward had no secondary bacterial infection (93%). More than half of patients admitted to the ICU developed secondary bacterial infection (56%). ROC analysis of highest PCT resp. CRP and secondary infection yielded AUCs of 0.88 (p < 0.001) resp. 0.86 (p < 0.001) for the entire cohort. With a PCT cut-off value at 0.55 ng/mL, the sensitivity was 91% with a specificity of 81%; a CRP cut-off value at 172 mg/L yielded a sensitivity of 81% with a specificity of 76%. CONCLUSION: PCT and CRP measurement on admission and during the course of the disease in patients with COVID-19 may be helpful in identifying secondary bacterial infections and guiding the use of antibiotic therapy.

Antimicrobial resistance in patients with decompensated liver cirrhosis and bacterial infections in a tertiary center in Northern Germany.

BACKGROUND AND AIMS: Bacterial infections are common in patients with decompensated liver cirrhosis and a leading cause of death. Reliable data on antibiotic resistance are required to initiate effective empiric therapy. We here aim to assess the antimicrobial resistance profile of bacteria among patients with liver cirrhosis and infection. METHODS: Overall, 666 cirrhotic patients admitted to Hannover Medical School between January 2012 and April 2018 with ascites were assessed for bacterial infection. In case of infection, bacteria cultured from microbiological specimens of ascites, blood or urine were identified and analyzed for resistances against common antibiotic agents. Furthermore, analyses compared two periods of time and community-acquired vs. nosocomial infections. RESULTS: In 281 patients with infection, microbiological sampling was performed and culture-positive results were obtained in 56.9%. Multidrug-resistant (MDR)-bacteria were found in 54 patients (19.2%). Gram-positive organisms were more common (n = 141/261, 54.0%) and detected in 116/192 culture-positive infections (60.4%). Comparing infections before and after 2015, a numerical decline for MDR-bacteria (23.8% vs. 15.6%, p = 0.08) was observed with a significant decline in meropenem resistance (34.9% vs. 19.5%, p = 0.03). MDR-bacteria were more frequent in the case of nosocomial infections. Of note, in ascites the majority of the tested bacteria were resistant against ceftriaxone (73.8%) whereas significantly less were resistant against meropenem (27.0%) and vancomycin (25.9%). CONCLUSIONS: In our tertiary center, distinct ratios of gram-positive infection with overall low ratios of MDR-bacteria were found. Adequate gram-positive coverage in the empiric therapy should be considered. Carbapenem treatment may be omitted even in nosocomial infection. In contrast, 3rd generation cephalosporins cannot be recommended even in community-acquired infection in our cirrhotic population.

The Primary Ciliary Dyskinesia Computed Tomography Score in Adults with Bronchiectasis: A Derivation und Validation Study.

BACKGROUND: Primary ciliary dyskinesia (PCD) is a rare genetic disorder which requires a complex diagnostic workup. Thus, an easy and widely available screening method would be helpful to identify patients who need a further diagnostic workup for PCD. OBJECTIVES: The aim of the study was to develop and validate a computed tomography (CT) score for PCD to facilitate etiological diagnosis in adults with bronchiectasis. METHOD: Chest CTs from 121 adults with bronchiectasis were scored for bronchiectasis morphology, distribution, and associated findings. Patients with and without the etiological diagnosis of PCD (46 and 75, respectively) were compared. Significantly, different imaging findings (p < 0.05) in univariate analysis were considered for multivariate analysis. Distinct findings were used to build the score. Based on this score, receiver operating characteristic (ROC) curve analysis was performed. The score was validated with 2 independent cohorts, another cohort from the same institution with 56 patients (28 with PCD) and an external cohort from another referral center with 172 patients (86 with PCD). RESULTS: The following parameters predicted PCD in adults with bronchiectasis and were included in the score with weighting according to their regression coefficients: 2 points were given for predominance in the middle/lower lobe, 2 points for tree-in-bud pattern, 2 points for atelectasis or prior resection of a middle/lower lobe, and 3 points for absence of emphysema and fibrosis. Situs inversus was only observed in subjects with PCD (Kartagener syndrome) and, thus, was not used in the primary ciliary dyskinesia computed tomography (PCD-CT) score as group comparisons could not be performed. ROC curve analysis revealed an area under the curve (AUC) of 0.90 (95% CI 0.85-0.96). Youden index was the highest at a threshold of >6 with a sensitivity of 83% and a specificity of 83%. In the validation cohorts, ROC curve analysis confirmed the performance of the score with an AUC of 0.83 (95% CI 0.72-0.94) in the first validation cohort and 0.79 (95% CI 0.73-0.86) in the external validation cohort. CONCLUSIONS: The PCD-CT score provides the first validated CT score for PCD and helps physicians in identifying adult bronchiectasis patients who require further diagnostic workup. Key message: The PCD-CT score provides the first validated CT score to assist physicians in identifying adult bronchiectasis patients who require a further diagnostic workup for PCD. It potentially improves earlier recognition of this rare and underdiagnosed disease.

Infection transmission among lung transplant couples.

The risk of transmission of infections in partnerships between 2 transplant recipients is unknown. The aim of this study was to evaluate transmission in such couples. In this single-center study, lung transplant (LTx) couples were identified among outpatients between 1988 and 2016. Infection rates per year and survival were compared to matched LTx-recipients not living in a transplant partnership. Twelve transplant couples were analyzed with cumulative 65 years of relationship. Overall infections were similar between LTx-couples and matched LTx-patients. No significant differences were noted in bacterial infections (.12 vs .27 per year), community-acquired viral (CARV) infections (.26 vs .22 per year), rejection treatments (.22 vs .12 per year), or hospitalizations (.26 vs .46 per year) in transplant couples and matched controls, respectively. There was no transmission of any microbial colonization from 1 partner to the other. Five cases of simultaneously detected CARV infections occurred (metapneumovirus [3], H1N1 [1], and respiratory syncytial virus [RSV; 1]). Three couples exhibited cytomegalovirus (CMV) reactivation in both partners at the same time with confirmed seronegativity before transplantation. In this case series of 12 lung transplant couples, the partnerships between 2 transplant recipients have no greater risk of bacterial infection and colonization transmission in comparison with recipients not living in a transplant relationship. However, transplant couples should be informed about the risk for transmission of viral infections, which could impact the development of chronic lung allograft dysfunction (CLAD).

Prevalence of Nontuberculous Mycobacterial Pulmonary Disease, Germany, 2009-2014.

We analyzed routine statutory health insurance claim data to determine prevalence of nontuberculous mycobacterial pulmonary disease in Germany. Documented prevalence rates of this nonnotifiable disease increased from 2.3 to 3.3 cases/100,000 population from 2009 to 2014. Prevalence showed a strong association with advanced age and chronic obstructive pulmonary disease.

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.

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.

Clinical Features, Diagnostic, Etiology, and Outcome 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.

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.

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 German Bronchiectasis Registry PROGNOSIS, 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.

Burden and trends of hospitalisations associated with pulmonary non-tuberculous mycobacterial infections in Germany, 2005-2011.

BACKGROUND: Representative population-based data on the epidemiology of pulmonary non-tuberculous mycobacterial (PNTM) infections in Europe are limited. However, these data are needed in order to optimise patient care and to facilitate the allocation of healthcare resources. The aim of the present study was to investigate the current burden and the trends of PNTM infection-associated hospitalisations in Germany. METHODS: International Classification of Diseases, 10th revision (ICD-10) discharge diagnosis codes were extracted from the official nationwide diagnosis-related groups (DRG) hospital statistics in order to identify PNTM infection-associated hospitalisations (ICD-10 code A31.0) between 2005 and 2011. Poisson log-linear regression analysis was used to assess the significance of trends. RESULTS: Overall, 5,959 records with PNTM infection as any hospital discharge diagnosis were extracted from more than 125 million hospitalisations. The average annual age-adjusted rate was 0.91 hospitalisations per 100,000 population. Hospitalisation rates increased during the study period for both males and females, with the highest rate of 3.0 hospitalisations per 100,000 population among elderly men, but the most pronounced average increase of 6.4%/year among females, particularly those of young and middle age, and hospitalisations associated with cystic fibrosis. Overall, chronic obstructive pulmonary disease (COPD) was the most frequent PNTM infection-associated condition in 28.9% of hospitalisations and also showed a significant average annual increase of 4.8%. CONCLUSIONS: The prevalence of PNTM infection-associated hospitalisations is steadily increasing in Germany. COPD is currently the most important associated condition. Our population-based study provides evidence of a changing epidemiology of PNTM infections and highlights emerging clinical implications.

[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.

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.

[Relevant biomarkers in infectiology]. / Relevante Biomarker in der Infektiologie.

A biomarker in infectiology should ideally be able to identify infectious agents, monitor clinical response and determine the duration of treatment. This article answers the question to what extent C-reactive protein and procalcitonin meet these requirements and reports on the search for further biomarkers - e.g. with the help of "omics"-based technologies and the integration of artificial intelligence.

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.