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Purpose: Over the course of COVID-19 pandemic, evidence has accumulated that SARS-CoV-2 infections may affect multiple organs and have serious clinical sequelae, but on-site clinical examinations with non-hospitalized samples are rare. We, therefore, aimed to systematically assess the long-term health status of samples of hospitalized and non-hospitalized SARS-CoV-2 infected individuals from three regions in Germany. Methods: The present paper describes the COVIDOM-study within the population-based cohort platform (POP) which has been established under the auspices of the NAPKON infrastructure (German National Pandemic Cohort Network) of the national Network University Medicine (NUM). Comprehensive health assessments among SARS-CoV-2 infected individuals are conducted at least 6 months after the acute infection at the study sites Kiel, Würzburg and Berlin. Potential participants were identified and contacted via the local public health authorities, irrespective of the severity of the initial infection. A harmonized examination protocol has been implemented, consisting of detailed assessments of medical history, physical examinations, and the collection of multiple biosamples (e.g., serum, plasma, saliva, urine) for future analyses. In addition, patient-reported perception of the impact of local pandemic-related measures and infection on quality-of-life are obtained. Results: As of July 2021, in total 6813 individuals infected in 2020 have been invited into the COVIDOM-study. Of these, about 36% wished to participate and 1295 have already been examined at least once. Conclusion: NAPKON-POP COVIDOM-study complements other Long COVID studies assessing the long-term consequences of an infection with SARS-CoV-2 by providing detailed health data of population-based samples, including individuals with various degrees of disease severity. Trial registration: Registered at the German registry for clinical studies (DRKS00023742). [ABSTRACT FROM AUTHOR]

Background: Antimicrobial stewardship (AMS) programs are effective tools for improving antibiotic prescription quality. Their implementation requires the regular surveillance of antibiotic consumption at the patient and institutional level. Our study captured and analyzed antibiotic consumption density (ACD) for hospitalized pediatric patients. Method: We collected antibacterial drug consumption data for 2020 from hospital pharmacies at 113 pediatric departments of acute care hospitals in Germany. ACD was calculated as defined daily dose (DDD, WHO/ATC Index 2019) per 100 patient days (pd). In addition, we analyzed the trends in antibiotic use during 2013–2020. Results: In 2020, median ACD across all participating hospitals was 26.7 DDD/100 pd, (range: 10.1–79.2 DDD/100 pd). It was higher at university vs. non-university hospitals (38.6 vs. 25.2 DDD/100 pd, p < 0.0001). The highest use densities were seen on oncology wards and intensive care units at university hospitals (67.3 vs. 38.4 DDD/100 pd). During 2013–2020, overall ACD declined (− 10%) and cephalosporin prescriptions also decreased (− 36%). In 2020, cephalosporins nevertheless remained the most commonly dispensed class of antibiotics. Interhospital variability in cephalosporin/penicillin ratio was substantial. Antibiotics belonging to WHO AWaRe "Watch" and "Reserve" categories, including broad-spectrum penicillins (+ 31%), linezolid (+ 121%), and glycopeptides (+ 43%), increased over time. Conclusion: Significant heterogeneity in ACD and prescription of different antibiotic classes as well as high prescription rates for cephalosporins and an increased use of reserve antibiotics indicate improvable antibiotic prescribing quality. AMS programs should urgently prioritize these issues to reduce antimicrobial resistance. [ABSTRACT FROM AUTHOR]

Purpose: Timely and accurate data on the epidemiology of sepsis are essential to inform policy decisions and research priorities. We aimed to investigate the validity of inpatient administrative health data (IAHD) for surveillance and quality assurance of sepsis care. Methods: We conducted a retrospective validation study in a disproportional stratified random sample of 10,334 inpatient cases of age ≥ 15 years treated in 2015–2017 in ten German hospitals. The accuracy of coding of sepsis and risk factors for mortality in IAHD was assessed compared to reference standard diagnoses obtained by a chart review. Hospital-level risk-adjusted mortality of sepsis as calculated from IAHD information was compared to mortality calculated from chart review information. Results: ICD-coding of sepsis in IAHD showed high positive predictive value (76.9–85.7% depending on sepsis definition), but low sensitivity (26.8–38%), which led to an underestimation of sepsis incidence (1.4% vs. 3.3% for severe sepsis-1). Not naming sepsis in the chart was strongly associated with under-coding of sepsis. The frequency of correctly naming sepsis and ICD-coding of sepsis varied strongly between hospitals (range of sensitivity of naming: 29–71.7%, of ICD-diagnosis: 10.7–58.5%). Risk-adjusted mortality of sepsis per hospital calculated from coding in IAHD showed no substantial correlation to reference standard risk-adjusted mortality (r = 0.09). Conclusion: Due to the under-coding of sepsis in IAHD, previous epidemiological studies underestimated the burden of sepsis in Germany. There is a large variability between hospitals in accuracy of diagnosing and coding of sepsis. Therefore, IAHD alone is not suited to assess quality of sepsis care. [ABSTRACT FROM AUTHOR]

Much of our knowledge about HIV infection has been obtained from cohort studies, including description of the natural history of infection, identification of CD4 count and viral load as good surrogate markers of clinical progression, identification of co-factors [including older age and viral infections (CMV, HCV)] for progression of HIV-related disease and assessment of impact of highly active antiretroviral therapy on clinical outcomes. The Cologne-Bonn cohort was founded by Gerd Fätkenheuer and Bernd Salzberger after introduction of combination antiretroviral therapy in 1996 and has delivered important findings which have helped to improve treatment strategies as well as quality of overall care in HIV infection in these two cities. Indeed, the first pivotal paper from the cohort reported on an unexpectedly high rate of virological treatment failure of protease inhibitor therapy in an unselected cohort of HIV-infected patients. The subsequent analysis of risk factors for virological failure initiated the development of more potent HIV combination therapy. This review summarizes some of the major findings and contributions from the Cologne-Bonn cohort since 1996. [ABSTRACT FROM AUTHOR]

It is a century-old tradition of furnishing Bibles in the bedside drawers of hospitalized patients. But since the books cannot be disinfected, it might be possible that bacterial pathogens survive on the bibles. The aim of this study was to determine whether Bibles in patient's rooms can act as a vehicle for the spread of nosocomial infections from one to the next patient. We took samples from 50 Bibles in various general wards of the hospital. During the same period, we took contact samples of 99 hymnals from the hospital chapel. The hospital chapel is visited by patients from all departments of the hospital. As expected, microorganisms were detected on all books. They were mainly apathogenic organisms. Molds ( Aspergillus spp.) were identified on the surfaces of five books. Two Bibles showed pathogen bacteria in a low number. No invasive infections with those pathogens could be documented during the investigation period, retrospectively. In conclusion, our results do not support Bibles as a possible source of nosocomial infections. [ABSTRACT FROM AUTHOR]

Purpose: Bacterial pneumonia, a major cause of respiratory tract infections (RTI), can be challenging to diagnose and to treat adequately, especially when seasonal viral pathogens co-circulate. The aim of this study was to give a real-world snapshot of the burden of respiratory disease and treatment choices in the emergency department (ED) of a tertiary care hospital in Germany in the fall of 2022. Methods: Anonymized analysis of a quality control initiative that prospectively documented all patients presenting to our ED with symptoms suggestive of RTI from Nov 7th to Dec 18th, 2022. Results: 243 patients were followed at the time of their ED attendance. Clinical, laboratory and radiographic examination was performed in 92% of patients (224/243). Microbiological work-up to identify causative pathogens including blood cultures, sputum or urine-antigen tests were performed in 55% of patients (n = 134). Detection of viral pathogens increased during the study period from 7 to 31 cases per week, while bacterial pneumonias, respiratory tract infections without detection of a viral pathogen and non-infectious etiologies remained stable. A high burden of bacterial and viral co-infections became apparent (16%, 38/243), and co-administration of antibiotic and antiviral treatments was observed (14%, n = 35/243). 17% of patients (41/243) received antibiotic coverage without a diagnosis of a bacterial etiology. Conclusion: During the fall of 2022, the burden of RTI caused by detectable viral pathogens increased unusually early. Rapid and unexpected changes in pathogen distribution highlight the need for targeted diagnostics to improve the quality of RTI management in the ED. [ABSTRACT FROM AUTHOR]

Introduction: Bloodstream infections with Enterococcus faecalis are associated with relevant morbidity and mortality. Targeted antimicrobial therapy is essential. The choice of an adequate treatment may be challenging when susceptibility testing offers different options. Selective reporting of antibiotic susceptibility test results might lead to a more tailored antibiotic therapy and could therefore be an important antimicrobial stewardship program intervention. The aim of this study was to analyse whether the introduction of selective reporting of antibiotic test results leads to a more targeted antibiotic therapy in patients with bloodstream infection with Enterococcus faecalis. Methods: This study was performed as a retrospective cohort study at the University Hospital Regensburg, Germany. All patients with blood cultures positive for Enterococcus faecalis between March 2003 and March 2022 were analysed. In February 2014 selective reporting of antibiotic susceptibility test results omitting sensitivity results for agents not recommended was introduced. Results: 263 patients with blood cultures positive for Enterococcus faecalis were included. After introduction of selective reporting of antibiotic tests (AI) significantly more patients received ampicillin than before introduction of selective reporting (BI) (9.6% BI vs. 34.6% AI, p < 0.001). Conclusion: Selective reporting of antibiotic susceptibility test results led to a significantly higher use of ampicillin. [ABSTRACT FROM AUTHOR]

The article informs about the introduction of mandatory masking in healthcare and the community in Jena, Germany, as a measure to control the spread of SARS-CoV-2. Topic include It reports a substantial drop in new infections among healthcare workers after the implementation of mandatory masking, and strict containment measures were introduced to further prevent the spread of the virus.

Purpose: SARS-CoV-2 infections cause COVID-19 and have a wide spectrum of morbidity. Severe disease courses among children are rare. To date, data on the variability of morbidity in relation to variant of concern (VOC) in children has been sparse and inconclusive. We compare the clinical severity of SARS-CoV-2 infection among children and adolescents in Germany during the Wildtype and Alpha combined, Delta and Omicron phases of the COVID-19 pandemic. Methods: Comparing risk of COVID-19-related hospitalization, intensive care unit (ICU) admission and death due to COVID-19 in children and adolescents, we used: (1) a multi-center seroprevalence study (SARS-CoV-2-KIDS study); (2) a nationwide registry of pediatric patients hospitalized with SARS-CoV-2 infections; and (3) compulsory national reporting for RT-PCR-confirmed SARS-CoV-2 infections in Germany. Results: During the Delta predominant phase, risk of COVID-19-related hospitalization among all SARS-CoV-2 seropositive children was 3.35, ICU admission 1.19 and fatality 0.09 per 10,000; hence about halved for hospitalization and ICU admission and unchanged for deaths as compared to the Wildtype- and Alpha-dominant period. The relative risk for COVID-19-related hospitalization and ICU admission compared to the alpha period decreased during Delta [0.60 (95% CI 0.54; 0.67) and 0.51 (95% CI 0.42; 0.61)] and Omicron [0.27 (95% CI 0.24; 0.30) and 0.06 (95% CI 0.05; 0.08)] period except for the < 5-year-olds. The rate of case fatalities decreased slightly during Delta, and substantially during Omicron phase. Conclusion: Morbidity caused by SARS-CoV-2 infections among children and adolescents in Germany decreased over the course of the COVID-19 pandemic, as different VOCs) emerged. [ABSTRACT FROM AUTHOR]

Purpose: Overweight and obesity have increased in people living with HIV (PLH). Our study evaluated weight, body-mass-index (BMI), and waist-to-hip ratio (WHR) change over 5 years of follow-up in PLH compared to the general population. Methods: HIV-positive participants in the HIV Heart Aging (HIVH) study were matched 1:2 by age and sex with HIV-negative controls of the population-based Heinz Nixdorf Recall (HNR) study. Both studies were recruited in the German Ruhr area. The association between HIV and weight, BMI, and WHR changes was examined using linear regression. Regression models were adjusted for parameters potentially affecting weight gain. Results: The matched HIVH and HNR participants (N = 585 and N = 1170, respectively; 14.7% females) had a mean age of 55 years at baseline. Despite the lower baseline weight (− 6 kg, 95% CI − 7.46 to − 4.59), the linear regression showed greater absolute and relative weight and BMI increases after 5 years in HIVH compared to HNR. Adjusting the linear regression models for smoking amplified that HIVH had a higher absolute and relative weight difference of 0.7 kg or ~ 1% compared to HNR after 5 years (95% Cl 0.1 to 1.3 and 0.2 to 1.6, respectively). Adjusting for HDL, LDL, systolic blood pressure, and diabetes mellitus did not affect the results. Conclusions: PLH had lower weight than the general population at baseline and after 5 years, but experienced greater increases in body weight after 5 years. WHR change after 5 years was lower in PLH compared to the general population, despite a higher WHR at baseline. [ABSTRACT FROM AUTHOR]

The SARS-CoV-2 pandemic has highlighted the importance of viable infection surveillance and the relevant infrastructure. From a German perspective, an integral part of this infrastructure, genomic pathogen sequencing, was at best fragmentary and stretched to its limits due to the lack or inefficient use of equipment, human resources, data management and coordination. The experience in other countries has shown that the rate of sequenced positive samples and linkage of genomic and epidemiological data (person, place, time) represent important factors for a successful application of genomic pathogen surveillance. Planning, establishing and consistently supporting adequate structures for genomic pathogen surveillance will be crucial to identify and combat future pandemics as well as other challenges in infectious diseases such as multi-drug resistant bacteria and healthcare-associated infections. Therefore, the authors propose a multifaceted and coordinated process for the definition of procedural, legal and technical standards for comprehensive genomic pathogen surveillance in Germany, covering the areas of genomic sequencing, data collection and data linkage, as well as target pathogens. A comparative analysis of the structures established in Germany and in other countries is applied. This proposal aims to better tackle epi- and pandemics to come and take action from the "lessons learned" from the SARS-CoV-2 pandemic. [ABSTRACT FROM AUTHOR]

Purpose: The severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) has caused substantial mortality worldwide. We investigated clinical and demographic features of COVID-19-related deaths that occurred between March 2020 and January 2022 in Regensburg, Germany. Methods: We compared data across four consecutive time periods: March 2020 to September 2020 (period 1), October 2020 to February 2021 (period 2), March 2021 to August 2021 (period 3), and September 2021 to January 2022 (period 4). Results: Overall, 405 deaths in relation to COVID-19 were reported. The raw case fatality ratio (CFR) was 0.92. In periods 1 to 4, the CFRs were 1.70%, 2.67%, 1.06%, and 0.36%. The age-specific CFR and mortality were highest in persons aged ≥ 80 years in period 2 while mortality in younger cases increased with time. The median age at death was 84 years and it varied slightly across periods. Around 50% of cases of death were previously hospitalized. In all time periods, the cause of death was mostly attributed to COVID-19. Over the four periods, we did not find significant changes in the distribution of sex and risk factors for severe disease. The most frequent risk factor was cardio-circulatory disease. Conclusion: In conclusion, the CFR decreased over time, most prominently for period 4. Mortality was considerable and younger cases were increasingly at risk. [ABSTRACT FROM AUTHOR]

Purpose: Recently, the German Medical Association introduced a new board certification in Internal Medicine and Infectious Diseases (ID). Accompanying, current experience with ID training and expectations for the new curriculum were assessed. Methods: After the development of a digital survey covering four main areas with 59 questions, it was distributed via the German Society for Infectious Diseases (DGI) and other networks following a snowball principle. Participation was carried out digitally in a web-based application. Results: Between December 2021 and February 2022, 300 datasets were included. 38.9% (114/293) of respondents had completed the additional training in ID. Of those, 54.0% (61/113) were concerned about recognition of previous training certification in the future after the establishment of the new sub-specialization. Overall, 78.5% (135/172) of respondents were satisfied or rather satisfied with the qualification gained through their training, but 8.7% (15/172) felt poorly prepared by their ID training. With regard to the inclusion of microbiology or antimicrobial stewardship (AMS) training into the new ID training curriculum, 84.6% (254/300) and 87.7% (263/300) of participants, respectively, desired an integration. Only 30.8% (53/172) felt sufficiently supported by their employer regarding childcare and 51.7% (89/172) reported missing support for scientific commitment. Conclusion: Overall, ID training in Germany seems satisfactory so far, but there is uncertainty about future recognition. Participants find that AMS and microbiology training should be integrated into new ID training curricula. New concepts regarding the compatibility of childcare and career as well as the support of scientific commitment seem essential to attract young professionals to the field. [ABSTRACT FROM AUTHOR]

Purpose: Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) is currently the major threat for immunocompromised individuals. The course of COVID-19 in lung transplant recipients in the Omicron era remains unknown. The aim of the study was to assess outcome and associated factors in lung transplant recipients in a German-wide multicenter approach. Methods: All affected individuals from January 1st to March 20th, 2022 from 8 German centers during the Omicron wave were collected. Baseline characteristics and antiviral measures were associated with outcome. Results: Of 218 patients with PCR-proven SARS-CoV-2 infection 166 patients (76%) received any early (< 7 days) antiviral therapy median 2 (interquartile range 1–4) days after symptom onset. Most patients received sotrovimab (57%), followed by remdesivir (21%) and molnupiravir (21%). An early combination therapy was applied in 45 patients (21%). Thirty-four patients (16%) developed a severe or critical disease severity according to the WHO scale. In total, 14 patients (6.4%) died subsequently associated with COVID-19. Neither vaccination and antibody status, nor applied treatments were associated with outcome. Only age and glomerular filtration rate < 30 ml/min/1.73m2 were independent risk factors for a severe or critical COVID-19. Conclusion: COVID-19 due to Omicron remains an important threat for lung transplant recipients. In particular, elderly patients and patients with impaired kidney function are at risk for worse outcome. Prophylaxis and therapy in highly immunocompromised individuals need further improvement. [ABSTRACT FROM AUTHOR]

Purpose: Following the emergency use authorization of BNT162b2 by the Food and Drug administration (FDA) in early December 2020, mRNA- and vector-based vaccines became an important means of reducing the spread and mortality of the COVID-19 pandemic. The European Medicines Agency labelled immune thrombocytopenia (ITP) as a rare adverse reaction of unknown frequency after vector-, but not mRNA-vaccination. Here, we report on the long-term outcome of 6 patients who were diagnosed with de-novo, vaccine-associated ITP (VA-ITP), and on the outcome of subsequent SARS-CoV-2 re-vaccinations. Methods: Patients were included after presenting to our emergency department. Therapy was applied according to ITP guidelines. Follow-up data were obtained from outpatient departments. Both mRNA- or vector-based vaccines were each used in 3 cases, respectively. Results: In all patients, the onset of symptoms occurred after the 1st dose of vaccine was applied. 5 patients required treatment, 3 of them 2nd line therapy. All patients showed a complete response eventually. After up to 359 days of follow-up, 2 patients were still under 2nd line therapy with thrombopoietin receptor agonists. 5 patients have been re-vaccinated with up to 3 consecutive doses of SARS-CoV-2 vaccines, 4 of them showing stable platelet counts hereafter. Conclusion: Thrombocytopenia after COVID-19 vaccination should trigger a diagnostic workup to exclude vaccine-induced immune thrombotic thrombocytopenia (VITT) and, if confirmed, VA-ITP should be treated according to current ITP guidelines. Re-vaccination of patients seems feasible under close monitoring of blood counts and using a vaccine that differs from the one triggering the initial episode of VA-ITP. [ABSTRACT FROM AUTHOR]

Purpose: Antibody assays against SARS-CoV-2 are used in sero-epidemiological studies to estimate the proportion of a population with past infection. IgG antibodies against the spike protein (S-IgG) allow no distinction between infection and vaccination. We evaluated the role of anti-nucleocapsid-IgG (N-IgG) to identify individuals with infection more than one year past infection. Methods: S- and N-IgG were determined using the Euroimmun enzyme-linked immunosorbent assay (ELISA) in two groups: a randomly selected sample from the population of Stuttgart, Germany, and individuals with PCR-proven SARS-CoV-2 infection. Participants were five years or older. Demographics and comorbidities were registered from participants above 17 years. Results: Between June 15, 2021 and July 14, 2021, 454 individuals from the random sample participated, as well as 217 individuals with past SARS-CoV-2 infection. Mean time from positive PCR test result to antibody testing was 458.7 days (standard deviation 14.6 days) in the past infection group. In unvaccinated individuals, the seroconversion rate for S-IgG was 25.5% in the random sample and 75% in the past infection group (P = < 0.001). In vaccinated individuals, the mean signal ratios for S-IgG were higher in individuals with prior infection (6.9 vs 11.2; P = < 0.001). N-IgG were only detectable in 17.1% of participants with past infection. Predictors for detectable N-IgG were older age, male sex, fever, wheezing and in-hospital treatment for COVID-19 and cardiovascular comorbidities. Conclusion: N-IgG is not a reliable marker for SARS-CoV-2 infection after more than one year. In future, other diagnostic tests are needed to identify individuals with past natural infection. [ABSTRACT FROM AUTHOR]

Purpose: The benefits of antiviral treatment with remdesivir in hospitalized patients with COVID-19 remain controversial. Clinical analyses are needed to demonstrate which patient populations are most likely to benefit. Methods: In a retrospective monocentric analysis, patients with COVID-19 treated between July 1, 2020 and June 30, 2021 at Hospital St. Georg, Leipzig, Germany were evaluated. The primary endpoint was time to clinical improvement, and the secondary endpoint was 28-day mortality. Propensity score matching was used for the endpoint analysis. Results: A total of 839 patients were fully evaluated, 68% of whom received specific COVID-19 drug therapy. Remdesivir was used in 31.3% of the patients, corticosteroids in 61.7%, and monoclonal antibodies in 2.3%. While dexamethasone administration was the most common therapeutic approach during the second pandemic wave, combination therapy with remdesivir and corticosteroids predominated during the third wave. Cox regression analysis revealed that combination therapy was not associated with faster clinical improvement (median: 13 days in both matched groups, HR 0.97 [95% CI 0.77–1.21], P = 0.762). By contrast, 28-day mortality was significantly lower in the corticosteroid-remdesivir group (14.8% versus 22.2% in the corticosteroid group, HR 0.60 [95% CI 0.39–0.95], P = 0.03) in the low-care setting. This effect was also demonstrated in a subgroup analysis of patients with remdesivir monotherapy (n = 44) versus standard of care (SOC). Conclusion: In COVID-19 patients with only mild disease (low-flow oxygen therapy and treatment in a normal ward) who received corticosteroids and/or remdesivir in addition to SOC, early administration of remdesivir was associated with a measurable survival benefit. [ABSTRACT FROM AUTHOR]

Purpose: Diphtheria, still present in many countries of the world, is caused by toxigenic strains of species of the Corynebacterium diphtheriae complex, mainly Corynebacterium diphtheriae and the emerging zoonotic pathogen C. ulcerans. The immunoprecipitation test according to Elek is the gold standard for detection of the major virulence factor diphtheria toxin (DT) in toxigenic corynebacteria. Due to its sophisticated methodological requirements, the classical Elek test is performed mainly by specialized reference laboratories. It was revealed that the current modification of the Elek test does not detect the toxin in weakly toxigenic isolates. Therefore, a more robust method for detecting free DT is urgently needed, especially for toxigenic C. ulcerans strains which are known to produce often much lower amounts of DT than C. diphtheriae. Methods: Thirty-one tox-positive C. ulcerans isolates with a negative standard Elek test result previously determined as NTTB (non-toxigenic tox bearing) were re-analyzed in this study using a modified immunoprecipitation method optimized regarding different parameters including type and concentration of antitoxin, medium volume, inoculum distance from the antitoxin disk and position of controls. Results: All 31 C. ulcerans strains tested positive in the optimized Elek test. Conclusion: Only with a reliable and easy-to-handle method for detecting the toxigenicity of C. ulcerans, it is possible to assess the etiological role of this emerging zoonotic bacterium in human pathology. [ABSTRACT FROM AUTHOR]

Purpose: Antibiotic exposure among hospitalized children is very high. With inappropriate antimicrobial use resulting in increased rates of antimicrobial resistance, the implementation of antibiotic stewardship programs is critically needed. This survey study aimed to identify current practice and knowledge about antibiotic stewardship and infection control among paediatricians in tertiary care paediatric hospitals in and around Munich, Germany. Methods: A prospective cross-sectional study based on an anonymous questionnaire, structured into different sub-sections regarding antibiotic use, antimicrobial resistance, antibiotic stewardship and infection control, was conducted between 1st of May and 30th of June 2016 in five paediatric hospitals. Results: In total, 111 paediatricians across all grades were eligible for participation. The overall proportion of correct answers for all sub-sections of the survey ranged from 54.1% correct answers in the antibiotic handling and bacterial resistance section to 72.9% correct answers in the hospital hygiene/infection control section. In general, knowledge across all categories was similar for junior doctors, middle-grade doctors or consultants. Advocating empiric use of narrow-spectrum instead of broad-spectrum antibiotics was considered to be the most difficult measure to implement in daily practice (36.9%). De-escalation from broad-spectrum empirical therapy to targeted treatment was considered the easiest measure to achieve (43.2%). Conclusion: Our results demonstrate that principles of antimicrobial stewardship and aspects of hospital hygiene/infection control are not satisfactorily known among hospital-based paediatricians in and around Munich. We identified four important target areas for future educational interventions that should play a more prominent role in both pre- and postgraduate medical training. [ABSTRACT FROM AUTHOR]

Purpose: First detected in China in 2019, the novel coronavirus disease (COVID-19) has rapidly spread globally. Since then, healthcare systems are exposed to major challenges due to scarce personnel and financial resources. Therefore, this analysis intended to examine treatment costs of COVID-19 inpatients in a German single centre during the first pandemic wave in 2020 from a healthcare payer perspective. Potential cost savings were assessed considering the administration of remdesivir according to the European Medicines Agency label. Methods: A retrospective medical-chart review was conducted on COVID-19 patients treated at University Hospital Cologne, Germany. Patients were clustered according to an eight-category ordinal scale reflecting different levels of supplemental oxygen. Potential cost savings due to the administration of remdesivir were retrospectively modelled based on a reduced length of stay, as shown in the Adaptive COVID-19 Treatment Trial. Results: 105 COVID-19 patients were identified. There was wide variability in the service data with median treatment costs from EUR 900 to EUR 53,000 per patient, depending on major diagnosis categories and clinical severity. No supplemental oxygen was needed in 40 patients (38.1%). Forty-three (41.0%) patients were treated in intensive-care units, and 30 (69.8%) received invasive ventilation. In our model, in-label administration of remdesivir would have resulted in costs savings of EUR 2100 per COVID-19 inpatient (excluding acquisition costs). Conclusion: We found that COVID-19 inpatients suffer from heterogeneous disease patterns with a variety of incurred G-DRG tariffs and treatment costs. Theoretically shown in the model, financial resources can be saved by the administration of remdesivir in eligible inpatients. [ABSTRACT FROM AUTHOR]

Purpose: Thorough knowledge of the nature and frequency of co-infections is essential to optimize treatment strategies and risk assessment in cases of coronavirus disease 2019 (COVID-19). This study aimed to evaluate the multiplex polymerase chain reaction (PCR) screening approach for community-acquired bacterial pathogens (CABPs) at hospital admission, which could facilitate identification of bacterial co-infections in hospitalized COVID-19 patients. Methods: Clinical data and biomaterials from 200 hospitalized COVID-19 patients from the observational cohort of the Competence Network for community-acquired pneumonia (CAPNETZ) prospectively recruited between March 17, 2020, and March 12, 2021 in 12 centers in Germany and Switzerland, were included in this study. Nasopharyngeal swab samples were analyzed on hospital admission using multiplex real-time reverse transcription (RT)-PCR for a broad range of CABPs. Results: In total of 200 patients Staphylococcus aureus (27.0%), Haemophilus influenzae (13.5%), Streptococcus pneumoniae (5.5%), Moraxella catarrhalis (2.5%), and Legionella pneumophila (1.5%) were the most frequently detected bacterial pathogens. PCR detection of bacterial pathogens correlated with purulent sputum, and showed no correlation with ICU admission, mortality, and inflammation markers. Although patients who received antimicrobial treatment were more often admitted to the ICU and had a higher mortality rate, PCR pathogen detection was not significantly related to antimicrobial treatment. Conclusion: General CABP screening using multiplex PCR with nasopharyngeal swabs may not facilitate prediction or identification of bacterial co-infections in the early phase of COVID-19-related hospitalization. Most patients with positive PCR results appear to be colonized rather than infected at that time, questioning the value of routine antibiotic treatment on admission in COVID-19 patients. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (Covid-19) vaccination is essential to fight the pandemic. Health care workers (HCWs) are prioritized to get vaccinated, yet uptake of recommended vaccinations is known to be low in this group. In a tertiary care university hospital with a high number of Covid-19 patients in intensive care, 59.5% of surveyed staff (N = 2454) were willing to get vaccinated, 21.4% were unsure and 18.7% refused. Vaccine hesitancy was higher in female, younger and healthy employees without contact to Covid-19 patients; nurses (53.3%) were much less willing to get vaccinated compared to physicians (82.7%). [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the diagnostic reliability and practicability of self-collected oropharyngeal swab samples for the detection of SARS-CoV-2 infection as self-sampling could enable broader testing availability and reduce both personal protective equipment and potential exposure. Methods: Hospitalized SARS-CoV-2-infected patients were asked to collect two oropharyngeal swabs (SC-OPS1/2), and an additional oropharyngeal swab was collected by a health care professional (HCP-OPS). SARS-CoV-2 PCR testing for samples from 58 participants was performed, with a 48-h delay in half of the self-collected samples (SC-OPS2). The sensitivity, probability of concordance, and interrater reliability were calculated. Univariate and multivariate analyses were performed to assess predictive factors. Practicability was evaluated through a questionnaire. Results: The test sensitivity for HCP-OPS, SC-OPS1, and SC-OPS2 was 88%, 78%, and 77%, respectively. Combining both SC-OPS results increased the estimated sensitivity to 88%. The concordance probability between HCP-OPS and SC-OPS1 was 77.6% and 82.5% between SC-OPS1 and SC-OPS2, respectively. Of the participants, 69% affirmed performing future self-sampling at home, and 34% preferred self-sampling over HCP-guided testing. Participants with both positive HCP-OPS1 and SC-OPS1 indicating no challenges during self-sampling had more differences in viral load levels between HCP-OPS1 and SC-OPS1 than those who indicated challenges. Increasing disease duration and the presence of anti-SARS-CoV-2-IgG correlated with negative test results in self-collected samples of previously confirmed SARS-CoV-2 positive individuals. Conclusion: Oropharyngeal self-sampling is an applicable testing approach for SARS-CoV-2 diagnostics. Self-sampling tends to be more effective in early versus late infection and symptom onset, and the collection of two distinct samples is recommended to maintain high test sensitivity. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to determine the proportion of people living with HIV with anti-SARS-CoV-2 IgG antibodies in a sample from a large single HIV center in Munich, Germany, after the first phase of the coronavirus pandemic and to infer the prevalence of SARS-CoV-2 co-infection in people living with HIV. Methods: Prospective sub-study of the ongoing ArcHIV cohort between May and July 2020. Anti-SARS-CoV-2 IgG antibodies were measured using the recomWell SARS-CoV-2 IgG ELISA (Mikrogen, Neuried, Germany); positive and borderline results were re-tested using the recomLine SARS-CoV-2 IgG immunoassay (Mikrogen, Neuried, Germany). Demographic and medical data were extracted from the electronic patient files. Results: Overall, 500 people living with HIV were included in the study (83% male, median age 51 years). Three participants had been diagnosed with COVID-19 prior to study inclusion. Of those, nine were confirmed positive for SARS-CoV-2 IgG antibodies, resulting in an estimated seroprevalence (accounting for sensitivity and specificity of the test) of 1.5% (CI 95%: 0.69; 3.13) for the entire study sample, and 2.2% (CI 95%: 1.1; 3.9) for the subset of the Munich citizens. There were no marked differences for people living with HIV with and without SARS-CoV-2 co-infection. Conclusion: The seroprevalence of SARS-CoV-2 co-infection in people living with HIV as found in our study does not seem to exceed previous reports from general populations of 'hot-sport' areas; comparative data from the Munich population can be expected to be published soon. Our data also highlight, once more, the need to do confirmatory testing on positive samples to minimize the impact of false-positive results. [ABSTRACT FROM AUTHOR]

Purpose: On January 1st 2019, the new EUCAST definitions of susceptibility testing categories S, I and R took effect. The changes in the I category have considerable clinical impact because they lead to major changes in the antibiogram, and misinterpretation may result in inappropriate selection and dosing of antibiotics hampering effective treatment of infectious diseases. We assessed if German physicians are aware of the new definitions and their consequences. Methods: We conducted a nationwide web-based survey to assess the knowledge on the new definitions of S, I and R. The survey was addressed to clinicians across all medical specialties working in Germany and was open from May 9th to July 30th 2019. Results: The answers of 902 participants were included in the analysis. Most participants were employed at hospitals (79.3%) and had already completed specialist training (86.1%). The predominant specialty was internal medicine (50.6%). Of all participants, 45.7% did not know that there was a change in the definitions of S, I and R, and 65.4% did not feel well-informed about the changes. When the participants had to identify true and false statements regarding the new I, substantial knowledge gaps were apparent. Worst results were achieved by those physicians who are not employed in a hospital but work in their own practice. Conclusion: Our survey shows that German physicians are insufficiently informed about the new definitions of S, I and R. Further education is strongly needed to ensure optimal treatment of infectious diseases. [ABSTRACT FROM AUTHOR]

Purpose: Current German/Austrian antiretroviral treatment guidelines recommend more than 20 combination regimens for first-line therapy, without a preference. Regimens include two nucleoside reverse transcriptase inhibitors (NRTIs) plus either an integrase strand transfer inhibitor (INSTI), a non-NRTI (NNRTI) or a boosted protease inhibitor (PI). The objective was to examine the outcomes of recommended first-line ART in Germany. Methods: This nationwide observational study included treatment-naïve chronically HIV-1 infected patients receiving one of the recommended first-line regimens. Patients were allocated to three arms (INSTI, NNRTI, PI) and were prospectively followed for 24 months. Delayed treatment initiation was defined by a baseline CD4 T-cell count of < 350/µl or CDC clinical stage C. Results: Among a total of 434 patients enrolled, virologic failure was rare and occurred in 4.3% (6/141) in the PI arm, in 3.3% (4/122) in the NNRTI arm and in 0.6% (1/171) in the INSTI arm (p = 0.10). De novo drug resistance mutations developed in only two patients in the NNRTI arm. Nonetheless, treatment modifications were frequent (51%) and mostly performed for strategic reasons. Retention on all initial compounds at month 24 was 64%, 49%, and 22% in the INSTI, NNRTI and PI arms respectively. Delayed treatment initiation was common (47%) and more frequently observed in patients in the PI arm. It was not associated with virological failure. Conclusion: High efficacy and low virological failure rates were observed with recommended first-line regimens independent of delayed treatment initiation, chosen regimen and subsequent treatment modifications, demonstrating the validity of the current treatment guidelines. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to analyse temporal changes in the epidemiology of candidemia assessing patient's characteristics, risk factors, diagnostic management, treatment, and outcome in a tertiary care hospital in South Eastern Germany. Methods: In this retrospective cohort study patients with blood cultures positive for Candida spp. were identified from the microbiological database in the years 2006–2018. A detailed collection of patients' characteristics was obtained for the time periods 2006–2008 and 2016–2018. Risk factors for survival were analysed in a logistic regression analysis. Results: In the years 2006–2018, a total of 465 episodes of candidemia were identified. An increase in candidemia cases was evident in the period of 2016–2018 compared to 2006–2015 and to 2006–2008 in absolute numbers and adjusted to patient-days. C. albicans was responsible for 62.8% of cases in 2006–2008 and 51.2% of all cases in the years 2016–2018, respectively, whereas there was a significant increase of C. glabrata in the latter period (16.3–31.5%). Overall mortality was not significantly different in the two periods. Infectious diseases consultation led to a lower mortality of patients with candidemia and to a higher adherence to guidelines. In multivariate analysis, only complete change or extraction of intravascular indwelling material and female gender were independent predictors for survival. Conclusion: We observed an increase in candidemia rates and rates of non-albicans spp. over time. A complete change of all catheters and/or indwelling devices improved survival. ID consultation led to a better guideline adherence. [ABSTRACT FROM AUTHOR]

In July 2018, brucellosis was diagnosed in a German patient without a travel history to regions endemic for Brucella. Microbiological analysis, including whole-genome sequencing, revealed Brucella suis biovar 1 as the etiologic agent. Core-genome-based multilocus sequence-typing analysis placed the isolate in close proximity to strains originating from Argentina. Notably, despite a strong IgM response, the patient did not develop Brucella-specific IgG antibodies during infection. Here, we describe the clinical course of infection, the extensive epidemiological investigations, and discuss possible routes of transmission. [ABSTRACT FROM AUTHOR]

Purpose: To determine whether changing from a tenofovir disoproxil fumarate (TDF)- to a tenofovir alafenamide fumarate (TAF)-containing regimen is correlated with weight changes in a human immunodeficiency virus (HIV)-positive adult cohort.Methods: Retrospective analysis was conducted of data gathered from routine care in a university hospital in Munich, Germany, between July 2015 and June 2017. Data from patients' charts were extracted and a two-step approach was applied. First, weight/BMI progression within 1 year after initiation of either TDF or TAF was compared. Subsequently, weight measurements within subjects changing from a TDF- to a TAF-containing antiretroviral regimen were analyzed by means of a repeated measurements general linear model.Results: After 360 days of initiating TAF, patients showed a mean (± standard deviation) percentual weight increase of 3.17 ± 0.21, whereas after 360 days of initiating TDF, patients only showed a mean (± standard deviation) percentual weight increase of 0.55 ± 0.17. The repeated measurements general linear model for within-subjects design showed a statistically significant correlation in weight after changing from a TDF to a TAF containing antiretroviral regimen. The weight difference between the two measurements while on TDF was not statistically significant, but every measure after switching to TAF was significantly higher than the previous.Conclusion: Changing from a TDF- to a TAF-containing regimen is correlated with weight gain in this retrospectively analyzed real-world cohort in Munich, Germany. [ABSTRACT FROM AUTHOR]

Purpose: Involvement of infectious disease (ID) specialists in the care of hospitalized patients with infections through consultation services improves the quality of care and the outcome of patients. This survey aimed to describe activities and utilization of ID consultations at four German tertiary care hospitals.Methods: A 1-month (March 2016) retrospective cross-sectional study at four university hospitals (Freiburg, Jena, Cologne and Regensburg) was performed. Only ID consultations with written documentation and bedside patient evaluation were included. Consultations were analyzed with regard to requesting departments, infections, case severity, and diagnostic and therapeutic recommendations.Results: In the study period, 638 ID consultations were performed in 479 patients—corresponding to 3-4 consultations per 100 inpatient cases. Patients were characterized by a high disease complexity—the mean case mix index in patients with consultation was 10.1 compared to 1.6 for all patients. ID consultations were requested by many different specialties, with approximately half of the requests coming from surgical disciplines. ID consultations resulted in revised diagnoses in 34% of the cases, provided recommendations for additional diagnostic procedures in 66%, and for modifications of antimicrobial regimens in 70% of the cases.Conclusions: Infectious disease consultations were requested for patients with severe and complicated diseases and resulted in recommendations that highly impacted the diagnostic work-up and therapeutic management of patients. The results of this survey may help to estimate requirements for establishment of such services in Germany. [ABSTRACT FROM AUTHOR]

Purpose: In 2016, the number of refugees worldwide reached 65.6 million. So far, only limited data are available on the health status of refugees and asylum seekers (RAs). Especially, notifiable infectious diseases (NIDs) carry the risk of outbreaks in communal accommodations hosting RAs.Methods: We conducted a monocentric retrolective cross-sectional study including 15,137 RAs treated in a special health care unit for RAs located in the major reception center in Munich from November 2014 to October 2016. Altogether 811 RAs with NIDs according to sections 6 and 7 of the German Infection Protection Act or with other infections relevant in the setting of a communal accommodation (RIDs) could be identified.Results: The gender and age distribution was generally comparable to that of refugees in Germany. However, patients from East Africa and Nigeria were significantly overrepresented. NIDs/RIDs were dominated by cases of tuberculosis, hepatitis B, and vaccine-preventable and parasitic diseases. Significant risk factors included country of origin (COI) and age for hepatitis B, age for hepatitis C, gender and age for HIV, and COI, gender and age for tuberculosis and ectoparasitosis. Calculated prevalences of hepatitis B, hepatitis C, and HIV were mostly below those of the COI. Incidences of tuberculosis were mostly strongly elevated.Conclusions: COI, gender, and age have an impact on the occurrence of NIDs/RIDs. Early vaccinations and improved hygiene could be effective in preventing NIDs/RIDs in communal accommodations. Screening, prompt therapy, and infection protection measures are necessary to prevent the transmission of diseases. [ABSTRACT FROM AUTHOR]

Purpose: The prevalence of protective anti-diphtheria toxin antibodies decreases with age. Therefore, the elderly might serve as reservoir for potentially toxigenic Corynebacterium ( C.) species ( C. diphtheriae, C. ulcerans, and C. pseudotuberculosis). This study aimed to examine the colonization rate of the nasopharynx with corynebacteria of individuals aged 65 years and older. Methods: In the period from October 2012 to June 2013, nasal and throat swabs were taken from 714 asymptomatic subjects aged 65-106 years (average age 77.2) at three regions in Germany and investigated for Corynebacterium species. Results: A total of 402 strains of Corynebacterium species were isolated from 388 out of 714 asymptomatic subjects (carriage rate 54.3%). The carriage rate was significantly higher in study participants living in retirement homes (68.4%) compared to those living autonomously at home (51.1%). Strains were isolated mostly from the nose (99%). Corynebacterium accolens was the most often isolated species (39.8%), followed by C. propinquum (24.1%), C. pseudodiphtheriticum (19.4%), and C. tuberculostearicum (10.2%). No C. diphtheriae, C. ulcerans, and C. pseudotuberculosis strains were isolated. A subsample of 74 subjects was tested serologically for anti-diphtheria antibodies. Protective anti-diphtheria toxin antibodies were found in 29.7% of the subjects; 70.3% showed no protective immunity. Conclusions: These results suggest that carriage of potentially toxigenic corynebacteria is very rare among people aged 65 and older in Germany. However, the low prevalence of protective anti-diphtheria toxin antibodies might pose a risk for acquiring diphtheria especially for the elderly. [ABSTRACT FROM AUTHOR]

Purpose: Blood culture (BC) sampling rates in Germany are considerably lower than recommended. Aim of our study was to assess knowledge, attitudes, and practice of physicians in Germany regarding BC diagnostics. Methods: We conducted a cross-sectional mixed-methods study among physicians working in inpatient care in Germany. Based on the results of qualitative focus groups, a questionnaire-based quantitative study was conducted in 2015-2016. In total, 706 medical doctors and final-year medical students from 11 out of 16 federal states in Germany participated. Results: BC sampling was considered an important diagnostic tool by 95% of the participants. However, only 23% of them would collect BCs in three scenarios for which BC ordering is recommended by present guidelines in Germany; almost one out of ten physicians would not have taken blood cultures in any of the three scenarios. The majority of participants (74%) reported not to adhere to the guideline recommendation that blood culture sampling should include at least two blood culture sets from two different injection sites. High routine in blood culture sampling, perceived importance of blood culture diagnostics, the availability of an in-house microbiological lab, and the department the physician worked in were identified as predictors for good blood culture practice. Conclusion: Our study suggests that there are substantial deficits in BC ordering and the application of guidelines for good BC practice in Germany. Based on these findings, multimodal interventions appear necessary for improving BC diagnostics. [ABSTRACT FROM AUTHOR]

Purpose: Few individuals that are latently infected with M. tuberculosis latent tuberculosis infection(LTBI) progress to active disease. We investigated risk factors for LTBI and active pulmonary tuberculosis (PTB) in Germany. Methods: Healthy household contacts (HHCs), health care workers (HCWs) exposed to M. tuberculosis and PTB patients were recruited at 18 German centres. Interferon-γ release assay (IGRA) testing was performed. LTBI risk factors were evaluated by comparing IGRA-positive with IGRA-negative contacts. Risk factors for tuberculosis were evaluated by comparing PTB patients with HHCs. Results: From 2008-2014, 603 HHCs, 295 HCWs and 856 PTBs were recruited. LTBI was found in 34.5% of HHCs and in 38.9% of HCWs. In HCWs, care for coughing patients ( p = 0.02) and longstanding nursing occupation ( p = 0.04) were associated with LTBI. In HHCs, predictors for LTBI were a diseased partner (odds ratio 4.39), sexual contact to a diseased partner and substance dependency (all p < 0.001). PTB was associated with male sex, low body weight ( p < 0.0001), alcoholism (15.0 vs 5.9%; p < 0.0001), glucocorticoid therapy (7.2 vs 2.0%; p = 0.004) and diabetes (7.8 vs. 4.0%; p = 0.04). No contact developed active tuberculosis within 2 years follow-up. Conclusions: Positive IGRA responses are frequent among exposed HHCs and HCWs in Germany and are poor predictors for the development of active tuberculosis. [ABSTRACT FROM AUTHOR]

Purpose: Peripheral facial nerve palsy (FP) is the most common single nerve affection. Most cases are idiopathic, but a relevant fraction is caused by potentially treatable aetiologies including infections. Not all current diagnosis and treatment guidelines recommend routine cerebrospinal fluid (CSF) analysis in the diagnostic workup of this symptom. In this study, we evaluated frequency of aetiologies and relevance of CSF analysis in an interdisciplinary cohort. Methods: We retrospectively analysed all cases of newly diagnosed FP treated at a German university medical centre in a 3-year period. Diagnostic certainty was classified for infectious aetiologies according to clinical and CSF parameters. Results: 380 patients with FP were identified, 63 children and 317 adults. Idiopathic Bell´s palsy was predominant in 61 %. 25 % of FP was attributed to infections, and other causes were identified in 14 %. Clinical presentation alone was not conclusive for infectious aetiology, in almost half of patients with infection-attributed FP the reported symptoms or clinical signs did not differ from common symptoms of idiopathic Bell`s palsy. Determination of C-reactive protein or white blood cell count was not helpful in the identification of infectious causes, and radiological imaging was performed in a high proportion of adult patients without conclusive results. Nuchal rigidity was found only in 7 % of patients with CSF pleocytosis. The predominant infectious agents were Borrelia burgdorferi, VZV and HSV, and in most of these cases diagnosis relied on the findings of CSF analysis. Conclusions: This study outlines the importance of careful differential diagnosis to identify infectious causes of facial nerve palsy. The high incidence and frequent unspecific clinical presentation of infectious FP underlines the importance of including CSF analysis in the diagnostic routine workup of FP. [ABSTRACT FROM AUTHOR]

Purpose: We retrospectively evaluated blood culture (BC) isolates of coagulase-negative staphylococci other than Staphylococcus epidermidis (NonSe-CoNS) for clinical relevance at a tertiary care hospital in Germany from January 2011 to September 2015. Methods: Clinical data were correlated to microbiological results based on medical records. Infection was considered likely if (1) no other infection and (2) two or more isolates of the same species were present and (3) symptoms ameliorated after therapy. Infection was considered possible if a foreign body was present and (1) and (3) were fulfilled. All the other cases were considered contaminations. Results: 313 patients with blood cultures positive for NonSe-CoNS were identified. 61 patients were excluded, either because of missing data or multiple pathogens in the same blood culture. Of the remaining 252 patients, 58 (23 %) were classified as possible ( n = 32) or likely ( n = 26) infections. S. haemolyticus was the most frequent isolate (infection: n = 28), followed by S. hominis ( n = 13), S. capitis ( n = 12), and S. lugdunensis ( n = 3). One patient died from NonSe-CoNS infection. The source of infection in the majority of patients was foreign bodies ( n = 43), and endocarditis was present in six cases. Staphylococci always considered contaminations were: S. auricularis, S. caprae, S. schleiferi, S. pettenkoferi, S. saccharolyticus, and S. simulans. The growth of NonSe-CoNS in the anaerobic BC bottle only and a time to positivity >36 h were associated with contaminations. Conclusions: One out of four NonSe-CoNS isolates was clinically relevant in our cohort, where S. haemolyticus, S. capitis, S. hominis, and S. lugdunensis contributed to 96.6 % of all relevant infections. [ABSTRACT FROM AUTHOR]

Purpose: In 2013, the German Commission for Hospital Hygiene and Infectious Disease Prevention (KRINKO) stated that extending weekly colonisation screening from very low birth weight (VLBW) infants (<1500 g) to all patients in the Neonatal Intensive Care Unit (NICU) might be useful. Methods: After implementing this recommendation, we detected a previously unnoticed cluster of Serratia marcescens. Strains were typed by Pulsed Field Gel Electrophoresis (PFGE). Results: Over 6 months, 19 out of 159 infants acquired S. marcescens. Twelve of the nineteen patients with S. marcescens were non-VLBW infants, and they were colonised significantly earlier than were VLBW infants (median 17 vs. 28 days; p < 0.01). Molecular typing revealed a polyclonal outbreak with multiple strain types leading to one or two transmissions each and a dominating outbreak strains being involved in an explosive outbreak involving eight neonates. Conclusion: The revised KRINKO recommendation may help identify unnoticed outbreaks. Colonised non-VLBW patients may be an underestimated source of S. marcescens. [ABSTRACT FROM AUTHOR]

Purpose: The current extent of migration poses emerging socio-economic and humanitarian challenges. Little is known on vaccination rates in migrants entering Europe, and the implementation of guidelines for serological testing and vaccination of refugees are pending. Methods: We conducted seroprevalence analyses for measles, mumps, rubella and varicella (MMRV) in 678 refugees coming to Germany during the current crisis. Results: The mean age of refugees was 28.8±11.4 years, and 76.1 % of subjects were male. Overall, IgG seronegativity was 7.4 % (95 % CI 5.5-9.6) for measles, 10.2 % (95 % CI 8.0-12.5) for mumps, 2.2 % (95 % CI 1.2-3.4) for rubella, and 3.3 % (95 % CI 1.9-4.9) for varicella. Seropositivity rates were age-dependent with considerably low values in children. For example, overall MMR immunity was 90.9 % (95 % CI 88.8-93.1), but only 73.1 % of minor aged refugees displayed complete seroprevalence against all three diseases, and only 68.9 % of children and adolescents were completely MMRV immune. Conclusion: Our initial data set suggests overall satisfactory MMRV immunity in adult migrants coming to Europe, but the observed low MMRV seroprevalences in refugee children support thorough and prompt vaccination of young migrants entering Europe. Taken together, our data set underlines the urgent need to implement and validate vaccination guidelines for refugee care in the current crisis. [ABSTRACT FROM AUTHOR]

Purpose: Clostridium difficile infection (CDI) represents a significant economic healthcare burden, especially the cost of recurrent disease. Fidaxomicin produced significantly lower recurrence rates and higher sustained cure rates in clinical trials. We evaluated the cost-effectiveness and budget impact of fidaxomicin compared with vancomycin in Germany in the first-line treatment of patient subgroups with CDI at increased risk of recurrence. Methods: A semi-Markov model was used to compare the cost-effectiveness and budget impact of fidaxomicin vs. vancomycin from a payer perspective in Germany. The model cycle length was 10 days. The time horizon was 1 year. Model inputs were probability of clinical cure, 30-day probability of recurrence, and 30-day attributable mortality based on evidence from two randomized controlled trials comparing fidaxomicin and vancomycin in patients with CDI. Cost-effectiveness outcomes were cost per quality-adjusted life year gained, cost per bed-day saved, and cost per recurrence avoided. Results: Despite higher drug acquisition costs, fidaxomicin was dominant in the cancer subgroup (less costly and more effective) and cost-effective in the other subgroups, with incremental cost-effectiveness ratios vs. vancomycin ranging from €26,900 to €44,500. Hospitalization costs of the first-line treatment of CDI with fidaxomicin vs. vancomycin were lower in every patient subgroup, resulting in budget impacts ranging from −€1325 (in patients ≥65 years) to −€2438 (in cancer patients). Reductions in the cost of treating recurrence with fidaxomicin ranged from −€574.32 per patient in those receiving concomitant antibiotics to −€1500.68 per patient in renally impaired patients. Conclusions: In patient subgroups with CDI at increased recurrence risk, fidaxomicin was cost-effective vs. vancomycin, and less costly and more effective in patients with cancer. [ABSTRACT FROM AUTHOR]

Purpose: Infections and subsequent septicemia are major complications in neutropenic patients with hematological malignancies. Here, we identify biomarker candidates for the early detection of an infectious origin, and monitoring of febrile neutropenia (FN). Methods: Proteome, metabolome, and conventional biomarkers from 20 patients with febrile neutropenia without proven infection (FNPI) were compared to 28 patients with proven infection, including 17 patients with bacteremia. Results: Three peptides (mass to charge ratio 1017.4-1057.3; p-values 0.011-0.024), six proteins (mass to charge ratio 6881-17,215; p-values 0.002-0.004), and six phosphatidylcholines ( p-values 0.007-0.037) were identified that differed in FNPI patients compared to patients with infection or bacteremia. Seven of these marker candidates discriminated FNPI from infection at fever onset with higher sensitivity and specificity (ROC-AUC 0.688-0.824) than conventional biomarkers i.e., procalcitonin, C-reactive protein, or interleukin-6 (ROC-AUC 0.535-0.672). In a post hoc analysis, monitoring the time course of four lysophosphatidylcholines, threonine, and tryptophan allowed for discrimination of patients with or without resolution of FN (ROC-AUC 0.648-0.919) with higher accuracy compared to conventional markers (ROC-AUC 0.514-0.871). Conclusions: Twenty-one promising biomarker candidates for the early detection of an infectious origin or for monitoring the course of FN were found which might overcome known shortcomings of conventional markers. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed at assessing the burden and spectrum of infectious diseases (ID) in a Metropolitan population in Germany. Methods: A discharge database using ICD-10 codes enabled the identification of hospitalizations with infection-related diagnoses. All hospital admissions between 2009 and 2014 were analysed from 9 municipal hospitals serving approximately one-third of an urban population of 3.5 million people. Results: We identified 114,168 admissions with a primary (first-listed) ID diagnosis and 220,483 admissions with any-listed ID diagnosis, accounting for 8.9 % [95 % confidence interval (CI) 8.9-9.0 %] and 17.2 % (95 % CI 17.1-17.3) of all 1,284,559 admissions, respectively. Annually, 439,837 bed-days (range 413,707-488,520) were occupied by patients with an ID diagnosis, utilizing 22.8 % of total bed capacity. The median length of stay for patients with primary ID diagnosis and secondary ID diagnosis was 6 days (IQR 3-11) and 10 days (IQR 5-19), respectively. The most common diagnosis across all age groups was 'pneumonia' (22.8 and 16.2 % of ID admissions as primary and secondary diagnosis, respectively). In-hospital mortality was 6.8 % (95 % CI 6.6-6.9) and 8.9 % (95 % CI 8.7-9.1) for ID as primary and secondary diagnosis, respectively. Conclusion: Infectious diseases contribute significantly to the overall burden of disease in a health system caring for an urban German population. In view of the magnitude of ID's contribution, establishing more specialists in ID medicine and adjusting the reimbursements for managing infection-related admissions should be made a public health priority in Germany. [ABSTRACT FROM AUTHOR]

Purpose: Clostridium difficile associated diarrhoea (CDAD) is the most common cause of health-care-associated infectious diarrhoea. In the context of the German health-care system, direct and indirect costs of an initial episode of CDAD and of CDAD recurrence are currently unknown. Methods: We defined CDAD as presence of diarrhoea (≥3 unformed stools/day) in association with detection of Clostridium difficile toxin in an unformed faecal sample. Patients treated with metronidazole (PO or IV) and/or vancomycin (PO) were included. Comprehensive data of patients were retrospectively documented into a database using the technology of the Cologne Cohort of Neutropenic Patients (CoCoNut). Patients with CDAD were matched to control patients in a 1:1 ratio. Analysis was split in three groups: incidence group (CDAD patients without recurrence), recurrence group (CDAD patients with ≥1 recurrence) and control group (matched non-CDAD patients). Results: Between 02/2010 and 12/2011, 150 patients with CDAD (114 patients in the incidence and 36 (24 %) in the recurrence group) and 150 controls were analysed. Mean length of stay was: 32 (95 %CI: 30-37), 94 (95 %CI: 76-112) and 24 days (95 %CI: 22-27; P = <0.001), resulting in mean overall direct treatment costs per patient of €18,460 (95 %CI: €14,660-€22,270), €73,900 (95 %CI: €50,340-€97,460) and €14,530 (95 %CI: €11,730-€17,330; P = <0.001). In the incidence and recurrence group, the mean cumulative number of antibiotic CDAD treatment days was 11 (95 %CI: 10-12) and 36 (95 %CI: 27-45; P = <0.001). Conclusions: Especially CDAD recurrence was associated with excessive costs, which were mostly attributable to a significantly longer overall length of stay. Innovative treatment strategies are warranted to reduce treatment costs and prevent recurrence of CDAD. [ABSTRACT FROM AUTHOR]

Background: The consumption of antifungal agents increased over the last decade, resulting in the development of resistant organisms and causing a significant pharmaco economic burden. Antifungal drugs are widely used for the treatment of systemic fungal infections and high-risk patients, especially with severe hematological or oncological conditions. Up to date, there are no reliable and systematically reported data on the consumption of antifungal substances on a nationwide level available. The presented study gives an update to the previously published multicenter study investigating antifungal consumption in different settings from five university hospital centers in Germany from 2001 to 2003. Methods: Consumption data for systemic antifungal drugs were obtained through the hospital pharmacies for 2001-2003 and 2008-2011 regarding the medical and surgical services of five university hospital centers in Germany (A-E). Drug use densities were calculated as yearly RDDs/100 patient days. These calculations were performed for the surgical and medical services, and independently for surgical and medical ICUs, as well as for the hematology-oncology services. Results: We report an increased utilization of systemic antifungal drugs in both study periods. The mean drug use density (mean value of all 5 hospitals) in the medical services increased by 24 % between 2001 and 2003. In 2011, this value was 37 % above the level from 2001 (12.4 RDD/100 patient days in 2001, 15.4 RDD/100 patient days in 2003, 17.0 RDD/100 patient days in 2011). The 4-year average drug use density (2008-2011) of medical services ranged between 11.6 RDD/100 patient days (hospital E) and 23.8 RDD/100 patient days (hospital A). Drug use densities were in medical intensive care units 29.4 RDD/100 patient days and hematology-oncology services 49.9 RDD/100 patient days. Conclusions: Despite the variability of the prescribing patterns between the tertiary hospitals, the presented pharmaco-epidemiological data are a cornerstone for the initiation and implementation of effective antifungal stewardship programmes and might serve as important benchmarking information for other hospitals with similar structures and baseline settings. [ABSTRACT FROM AUTHOR]

Purpose: To assess rate of late presentation with HIV in Southwestern Germany and to identify patient characteristics correlated with CD4 nadir. Methods: Patients with primary diagnosis who presented to one of ten participating clinics rated on knowledge and behavior towards HIV testing on a self-developed questionnaire, whereas clinical data was assessed by the physician. Results: 161 patients were included. Risk factors were homosexual (59.5 %) or heterosexual contacts (26.8 %), drug use (2.0 %), migration (3.9 %), or others (7.8 %). 63.5 % had a CD4 T cell count < 350/µl. 52.5, 17.4, and 31.1 % were diagnosed in CDC stadium A, B or C, respectively. 209 disease episodes were reported, from whom 83.7 % had led to the diagnosis of HIV. 75.2 and 68.3 % said to have been well-informed about ways of transmission and testing offerings, respectively, and 20.4 % admitted to have psychologically repressed the possibility of being infected. 48 patients rated their personal behavioral risk as 'high' or 'very high'. Of these, however, only ten had performed at test in the precedent year. Performing a regression analysis, younger age and previous testing were correlated with a higher CD4 T cell nadir ( p = 0.005, and 0.018, resp.). Conclusion: The rate of late presentation in this region was even higher compared to national or European surveys. Most infected patients perceived to have had only a low risk. Several disease episodes did not lead to the initiation of HIV testing by the physician. [ABSTRACT FROM AUTHOR]

Purpose: We studied a cohort of adult patients with chronic hepatitis B (CHB) infection, followed at a tertiary referral liver center in Germany over 12.5 years to analyze the clinical features and impact of management on disease progression and survival of CHB patients in general and of those with CHB and HCC in particular. Methods: We retrospectively evaluated the medical records of 242 adult (age ≥ 18 years) patients. CHB was defined as positive hepatitis B surface antigen (HBsAg) and/or HBV-DNA levels >10 IU/mL for at least 6 months. Patient demographics, HBV markers, antiviral treatment, laboratory parameters, liver imaging and histology were recorded for each visit. HCC patients were divided into two groups and separately analyzed (group 1: n = 24, HCC at first visit and group 2: n = 11, HCC during surveillance). Results: The mean age was 44 years in CHB patients without HCC (63 % male) and about 59 years in patients with HCC (77 % male). Antiviral therapy was given to 59 % of patients without HCC compared to only 25 % in group 1 and 18 % in group 2 with comparable median HBV DNA levels of approximately 36,000 IU/mL. There was no statistically significant difference concerning the HCC stages (Milan, UCSF, BCLC) at first diagnosis. Five-year survival was 19 % in group 1 vs. 64 % in group 2 ( p = 0.019), with LTx performed in 12 vs. 45 %, respectively. Conclusion: Surveillance of CHB patients did not result in early stage detection of HCC but in a higher likelihood to receive potentially curative treatments. [ABSTRACT FROM AUTHOR]

Purpose: Standardized prevalence and incidence data on carbapenem-resistant organisms (CRO) and, as a relevant subgroup, carbapenem-resistant Enterobacteriaceae (CRE) are scarce. CRO-surveillance within the German nosocomial infection surveillance system (KISS) aims to provide epidemiological surveillance data on CRO colonizations and infections. Methods: CRO-surveillance is part of a KISS-module for the surveillance of multidrug-resistant organisms (MDRO). MDRO-KISS methods require surveillance of all patients admitted to the ward and standardized documentation of imported and ICU-acquired cases. Data on all MDRO-carriers including colonization and infection with MDRO are collected. All presented data were routine data collected from January 1st 2013 until December 1st 2013 in accordance with the German Protection against Infection Act (IfSG). Results: 341 ICUs submitted data on MDRO during the first year. In total, 5,171 cases of multidrug-resistant Gram-negative bacteria (MRGN) were identified. 848 were CRO (16 %). 325 CRO-cases were acquired within the ICU (38 %), and 373 CRO-patients had an infection (44 %). CRO-prevalence was 0.29 per 100 patients. Acquisition rate of MRGN was 1.32 per 1,000 patient days. This rate is more than doubled the acquisition rates of other MDRO under surveillance within MDRO-KISS (0.57 MRSA, 0.49 VRE). CRO-acquisition rate was 0.3 per 1,000 patient days. Incidence density of MRGN infections bacteria was 0.58 per 1,000 patient days (CRO 0.15/1,000 patient days). Conclusions: To date, CRO are common in German ICUs and the relatively large proportions of ICU-acquired CRO and infections emphasize their potential to cause outbreaks. High MRGN infection rates and high ESBL prevalence data from clinical studies suggest a lack of MRGN identification in asymptomatic carriers. [ABSTRACT FROM AUTHOR]

Background: The number of dengue cases imported to Germany has increased significantly in recent years. Among returning travelers, dengue is now a frequent cause of hospitalization. The aim of this study was to determine the proportion of patients with severe disease hospitalized in a European, non-endemic country applying the revised 2009 WHO classification system and to determine predictors of severe disease. Methods: A retrospective single-center analysis of clinical data from 56 patients, 31 (55 %) women and 25 (45 %) men, between 14 and 70 years of age treated in a tertiary care hospital between 1996 and 2010 was conducted. Results: Thirty-nine patients (69.6 %) presented with dengue fever without warning signs, 11 (19.6 %) with warning signs and 6 (10.7 %) with signs for severe dengue fever. Two patients (4 %) developed dengue shock syndrome. Non-European descent ( p = 0.001), plasma protein level <6.5 mg/dl ( p = 0.001), platelets <30/nl ( p = 0.017) and activated partial thromboplastin time (aPTT) >44 s ( p = 0.003) were associated with severe disease. Conclusions: A significant proportion of patients hospitalized with symptomatic imported dengue fever in Germany have evidence of severe disease. Simple routine laboratory parameters such as complete blood count, plasma protein level and aPTT are helpful tools for identifying adult patients at risk for severe disease. [ABSTRACT FROM AUTHOR]

Introduction: Tigecycline is an established treatment option for infections with multiresistant bacteria (MRB). It retains activity against many strains with limited susceptibility to other antibiotics. Efficacy and safety of tigecycline as monotherapy or in combination regimens were investigated in a prospective noninterventional study involving 1,025 severely ill patients in clinical routine at 137 German hospitals. Materials and methods: Data on the full population have been published; our present analysis focuses on infections caused by MRB. The study population included patients with complicated infections, high disease severity (APACHE II > 15: 65 %) and high MRB prevalence. Most patients had comorbidities, including cardiovascular disease, renal insufficiency, and/or diabetes mellitus. Treatment success was defined as cure/improvement without requirement of further antibiotic therapy. Results: Pathogens isolated from 215 evaluable patients with documented MRB infections included 132 methicillin-resistant Staphylococcus aureus (MRSA), 42 vancomycin-resistant Enterococci (VRE) and 67 Gram-negative extended beta-lactamase (ESBL) producers. Of the MRB subpopulation, 140 patients received tigecycline monotherapy, 75 were treated with combination regimens. High overall clinical success rates were recorded for MRB infections treated with tigecycline alone (94 %) or in combinations (88 %); in detail intraabdominal infections (monotherapy: 90 %; combinations: 93 %), skin/soft tissue infections (93; 100 %), community-acquired pneumonia (100; 100 %), hospital-acquired pneumonia (94,7; 72,7 %), diabetic foot infections (89; 33 %), blood stream infections (100; 100 %) and multiple-site infections (92; 71 %). Conclusions: Tigecycline achieved high clinical success rates in patients with documented infections involving MRB strains despite high disease severity. These results add to the evidence indicating that tigecycline is a valuable therapeutic option for complicated infections in severely ill patients with a high likelihood of multidrug-resistant pathogen involvement. [ABSTRACT FROM AUTHOR]

Purpose: The burden of extended-spectrum beta-lactamase (ESBL)-positive Enterobacteriaceae (ESBL-E) is growing worldwide. We aimed to determine the financial disease burden attributable to ESBL-positive species in cases of bloodstream infection (BSI) due to K. pneumoniae and E. coli. Methods: We conducted a cohort study on patients with BSI due to K. pneumoniae or E. coli between 2008 and 2011 in our institution. Data were collected on true hospital costs, length of stay (LOS), basic demographic parameters, underlying diseases as Charlson comorbidity index (CCI) and ESBL positivity of the pathogens. Multivariable regression analysis on hospital costs and length of stay was performed. Results: Overall we found 1,851 consecutive cases of ESBL-E BSI, 352 (19.0 %) cases of K. pneumoniae BSI and 1,499 (81.0 %) cases of E. coli BSI. Sixty-six of E. coli BSI (18.8 %) and 178 of K. pneumoniae BSI (11.9 %) cases were due to ESBL-positive isolates, respectively ( p = 0.001). 830 (44.8 %) cases were hospital-onset, 215 (61.1 %) of the K. pneumoniae and 615 (41.0 %) of the E. coli cases ( p < 0.001). In-hospital mortality was overall 19.8, 25.0 % in K. pneumoniae cases and 18.5 % in E. coli cases ( p = 0.006). Increased hospital costs and length of stay were significantly associated to BSI with ESBL-positive K. pneumoniae. Conclusion: In contrast to BSI due to ESBL-positive E. coli, cases of ESBL-positive K. pneumoniae BSI were associated with significantly increased costs and length of stay. Infection prevention measures should differentiate between both pathogens. [ABSTRACT FROM AUTHOR]