COVID or not COVID: attributing and reporting cause of death in a community cohort.

OBJECTIVES: In Germany, deaths of SARS-CoV-2-positive persons are reported as 'death related to SARS-CoV-2/COVID-19' to the Robert Koch Institute, Germany's main infectious disease institution. In 177 COVID-19-associated deaths reported in Regensburg, Germany, from October 2020 to January 2021, we investigated how deaths following SARS-CoV-2 infection were reported and whether cases with a death attributed to SARS-CoV-2 (COVID-19 death [CD]) differed from cases with a reported death from other causes (non-COVID-19 death [NCD]). STUDY DESIGN: This was an observational retrospective cohort study. METHODS: We analysed descriptive data on the numbers of cases, deaths, age, sex, symptoms and hospitalizations. We calculated odds ratios (ORs) with 95% confidence intervals (95% CIs) and performed Chi-squared/Fisher's exact test for categorical variables and the Wilcoxon rank-sum test for comparison of medians. RESULTS: Deaths attributed to COVID-19 occurred primarily in elderly patients. The mortality rate and the case fatality ratio (CFR) increased with age. The median age and the prevalence of risk factors were similar between CD and NCD. Respiratory symptoms and pneumonia at the time of diagnosis were associated with death reported as CD. The odds of CD attribution in cases hospitalized because of COVID-19 were 6-fold higher than the odds of NCD (OR: 6.00; 95% CI: 1.32 to 27.22). CONCLUSIONS: Respiratory symptoms/pneumonia at the time of diagnosis and hospitalization due to COVID-19 were associated with attributing a death to COVID-19. Numbers of COVID deaths need to be interpreted with caution. Criteria that facilitate attributing the cause of death among SARS-CoV-2 cases more uniformly could make these figures more comparable.

Recommendations for treatment of critically ill patients with COVID-19 : Version 3 S1 guideline.

Since December 2019 a novel coronavirus (severe acute respiratory syndrome coronavirus 2, SARS-CoV-2) has rapidly spread around the world resulting in an acute respiratory illness pandemic. The immense challenges for clinicians and hospitals as well as the strain on many healthcare systems has been unprecedented.The majority of patients present with mild symptoms of coronavirus disease 2019 (COVID-19); however, 5-8% become critically ill and require intensive care treatment. Acute hypoxemic respiratory failure with severe dyspnea and an increased respiratory rate (>30/min) usually leads to intensive care unit (ICU) admission. At this point bilateral pulmonary infiltrates are typically seen. Patients often develop a severe acute respiratory distress syndrome (ARDS).So far, remdesivir and dexamethasone have shown clinical effectiveness in severe COVID-19 in hospitalized patients. The main goal of supportive treatment is to ascertain adequate oxygenation. Invasive mechanical ventilation and repeated prone positioning are key elements in treating severely hypoxemic COVID-19 patients.Strict adherence to basic infection control measures (including hand hygiene) and correct use of personal protection equipment (PPE) are essential in the care of patients. Procedures that lead to formation of aerosols should be carried out with utmost precaution and preparation.

[The outbreak of COVID-19 in China]. / Der Ausbruch von COVID-19 in China.

The transmission dynamics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Wuhan and Hubei Province differ considerably from those in the rest of China. In Hubei province SARS-CoV­2 led to a dramatic outbreak. Intensive control measures (travel restrictions, isolation of cases, quarantine of contacts and others) led to the control of the outbreak. Despite travel restrictions SARS-CoV­2 was detected in other provinces in the following weeks. Consistent and intensive identification and isolation of infected persons ("containment") was able to prevent an outbreak outside Hubei province, providing an example for the control of SARS-CoV­2.

[Epidemiology of SARS-CoV-2 infection and COVID-19]. / Epidemiologie von SARS-CoV-2-Infektion und COVID-19.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a new ß­Coronavirus that was first detected in 2019 in Wuhan, China. In the ensuing months it has been transmitted worldwide. Here the authors present the current knowledge on the epidemiology of this virus. SARS-CoV­2 replicates mainly in the upper and lower respiratory tract and is primarily transmitted by droplets from asymptomatic and symptomatic infected subjects. The estimate for the basic reproduction number (R) is currently between 2 and 3, while the incubation period is 6 (median, range 2-14) days. Although most infections are uncomplicated, 5-10% of cases develop pneumonia, which can lead to hospitalization, respiratory failure and multiorgan failure. Risk factors for a complicated disease course include age, hypertension, chronic cardiovascular and pulmonary disease and immunodeficiency. The overall case fatality rate is 1.4%, with the rate rising in the sixth decade of life. Nosocomial and infections in medical personnel have been reported. Drastic reductions in social contact have been implemented in many countries with outbreaks of SARS-CoV­2, leading to rapid reductions in R. Which of the measures have been effective is still unknown.

[Antibiotic stewardship (ABS). Part 1: Basics]. / Antibiotic Stewardship (ABS). Teil 1: Grundlagen.

Against the background of increasing antimicrobial resistance, antibiotic stewardship (ABS) is an important measure to counteract the spread of resistant pathogens and multidrug resistance. For Germany and Austria, a comprehensive S3 guideline is available, which was last updated in 2018. The control of antibiotic or anti-infective use in hospitals should be guided by specialized ABS teams. At the hospital level, ABS also includes a structured ongoing analysis of local antibiotic use and resistance data. Recommendations for locally adapted therapy regimens should be derived and implemented from this data analysis. ABS consists of regular ward rounds ("ABS visits"), during which members of the ABS team review the indication, dosage, route of administration and duration of antimicrobial therapy at the bedside. Here, the key challenge is to save antibiotics without compromising the individual patient. Digitalization and artificial intelligence offer new options for ABS, while the adaption of inpatient concepts to outpatient care is also important.

[Antibiotic stewardship (ABS). Part 2: Application]. / Antibiotic Stewardship (ABS). Teil 2: Anwendung.

Antibiotic stewardship (ABS) is an important measure to counteract the spread of resistant pathogens and multidrug resistance. The most important ABS tools include the implementation of local guidelines, the development of a house-related list of anti-infective agents, regular ABS visits and practice-oriented internal training events. Effective strategies for therapy optimization include indication testing and therapy evaluation, dose optimization as well as determining an appropriate duration of therapy. Oralization of anti-infectives (sequence therapy) should be supported by consistent clinical criteria in in-house guidelines. The incidence of Clostridioides difficile infections (CDI) can be more than halved by restricting the so-called "4C antibiotics". Point-of-care tests help to minimize the use of antibiotics in the outpatient setting. Vaccination reduces the need for antibiotic therapy.

[Pneumocystis jirovecii pneumonia-an opportunistic infection undergoing change]. / Pneumocystis-jirovecii-Pneumonie ­ eine opportunistische Infektion im Wandel.

Pneumocystis jirovecii pneumonia (PcP) has for many years been reported mostly in human immunodeficiency virus-infected patients. Increasingly, it also affects other immunocompromised patients, e.g. after organ or allogeneic stem cell/bone marrow transplantation, patients with hematologic malignancies or autoimmune diseases. The diagnosis of PcP relies on a critical evaluation of clinical symptoms, risk factors, radiologic features and microbiological tests. High dose cotrimoxazole is the most effective therapeutic option. Rapid initiation is essential, since mortality is especially high in patients admitted to intensive care with respiratory failure. This article reviews the current epidemiology of PcP and highlights the diagnostic and therapeutic options. Recommendations for primary and secondary prophylaxis are summarized.

[Current treatment of endocarditis : Innovations and controversies]. / Aktuelle Therapie der Endokarditis : Neuerungen und Kontroversen.

Despite many novel diagnostic strategies and advances in treatment, infective endocarditis (IE) remains a severe disease. The epidemiology of IE has shifted and staphylococci have replaced streptococci as the most common cause and nosocomially acquired infections, invasive procedures, indwelling cardiac devices and acquired infections due to intravenous drug abuse are more frequent. The incidence of IE has steadily increased in recent years and the patients affected are older and have more comorbidities. The modern treatment of IE is interdisciplinary. The pharmacotherapy of IE depends on the pathogen and its sensitivity. The presence of a bioprosthetic valve and implantable cardiac devices plays a significant role in selection of antibiotics and duration of treatment. This article provides an update and overview of the current clinical practice in diagnostics and pharmacotherapy of IE in adults with a special focus on partial oral therapy and the role of aminoglycosides.

[Infectious diseases - a specialty of internal medicine]. / Infektiologie ­ ein Schwerpunkt der Inneren Medizin.

Infectious diseases have recently gained wide public interest. Emerging infections and rising rates of antibiotic resistance are determining this trend. Both challenges will need to be addressed in international and local collaborations between different specialties in medicine and basic science. Infectious diseases as a clinical specialty in this scenario is directly responsible for the care of patients with infectious diseases. Its involvement in the care of patients with complicated infections has proved to be highly effective. Antibiotic stewardship programmes are effective measures in slowing the development of antibiotic resistance and have been widely implemented. But antibiotic stewardship specialists should not be confused with or taken as an alternative to infectious disease experts. Infectious diseases requires appropriate and specific training. It mainly uses the instrumentarium of internal medicine. With the current challenges in modern medicine, infectious diseases in Germany should thus be upgraded from a subspecialty to a clinical specialty, ideally within Internal Medicine.

[Fecal microbiota transplantation]. / Fäkaler Mikrobiomtransfer.

The human intestinal microbiome has important metabolic and immunological functions for the host and is part of the defense against pathogens in the gastrointestinal tract. Antibiotics, probiotics, dietary measures, such as prebiotics, and the relatively newly established method of fecal microbiota transplantation (FMT, also known as fecal microbiome transfer) all influence the intestinal microbiome. The FMT procedure comprises the transmission of fecal microorganisms from a healthy donor into the gastrointestinal tract of a patient. The aim of this intervention is to restore a normal microbiome in patients with diseases associated with dysbiosis. The only indication for FMT is currently multiple recurrence of Clostridium difficile infections. Approximately 85% of affected patients can be successfully treated by FMT compared to only about 30% treated conventionally with vancomycin. Other possible therapeutic applications are chronic inflammatory and functional bowel diseases, insulin resistance and morbid obesity but these have to be evaluated further in clinical trials. Knowledge on the optimal donor, the best dosage and the most appropriate route of administration is still limited. A careful donor selection is necessary. The implementation of FMT in Germany is subject to the Medicines Act (Arzneimittelgesetz, AMG) with a duty of disclosure and personal implementation by the attending physician. By documentation in a central register long-term effects and side effects of FMT have to be evaluated.

PEPDar: A randomized prospective noninferiority study of ritonavir-boosted darunavir for HIV post-exposure prophylaxis.

OBJECTIVES: PEPDar compared the tolerability and safety of ritonavir-boosted darunavir (DRV/r)-based post-exposure prophylaxis (PEP) with the tolerability and safety of standard of care (SOC). The primary endpoint was the early discontinuation rate among the per-protocol population. METHODS: PEPDar was an open-label, randomized, multicentre, prospective, noninferiority safety study. Subjects were stratified by type of event (occupational vs. nonoccupational, i.e. sexual) and were randomized to receive DRV/r plus two nucleoside reverse transcriptase inhibitors (NRTIs) or SOC PEP. Twenty-two private or university HIV clinics in Germany participated. Subjects were ≥ 18 years old and had documented or potential HIV exposure and indication for HIV PEP. They initiated PEP not later than 72 h after the event and were HIV negative. RESULTS: A total of 324 subjects were screened, the per-protocol population was 305, and 273 subjects completed the study. One hundred and fifty-five subjects received DRV/r-based PEP and 150 subjects received ritonavir-boosted lopinavir (LPV/r)-based PEP for 28-30 days; 298 subjects also received tenofovir/emtricitabine. The early discontinuation rate in the DRV/r arm was 6.5% compared with 10.0% in the SOC arm (P = 0.243). Adverse drug reactions (ADRs) were reported in 68% of DRV/r subjects and 75% of SOC subjects (P = 0.169). Fewer DRV/r subjects (16.1%) had at least one grade 2 or 3 ADR compared with SOC subjects (29.3%) (P = 0.006). All grades of diarrhoea, nausea, and sleep disorders were significantly less frequent with DRV/r, while headache was significantly more frequent. No HIV seroconversion was reported during follow-up. CONCLUSIONS: Noninferiority of DRV/r to SOC was demonstrated. DRV/r should be included as a standard component of recommended regimens in PEP guidelines.

[Initial examination and screening of migrants : What makes sense and what is evidence-based?]. / Erstuntersuchung und Screening von Migranten : Was ist sinnvoll, was ist evidenzbasiert?

The medical treatment of migrants and refugees has recently become an important topic in the German healthcare system due to the large numbers of migrants. Healthcare for migrants includes treatment of acute illnesses and trauma on arrival, screening for chronic communicable and non-communicable diseases and in the long term, the integration into the local healthcare system. As health problems of migrants are diverse and dependent on the region of origin, guidelines should be readily available for all healthcare professionals involved in migrant healthcare. A literature search for comprehensive guidelines for screening and treatment of migrant's health problems detected 47 different guidelines including 2 comprehensive ones from the US Centers of Disease Control and Prevention and the Canadian Collaboration for Immigrant and Refugee Health. Comparative analysis of these guidelines could be a starting point for evidence-based European guidelines on migrant health.

Outcome-related co-factors in 105 cases of vertebral osteomyelitis in a tertiary care hospital.

PURPOSE: Vertebral osteomyelitis (VO) is an infection of the vertebral body and the adjacent disc space. The aim of our study was to identify outcome-related co-factors of patients with VO treated in the last decade. METHODS AND RESULTS: We retrospectively identified 105 patients with VO (mean age 66.1 years) who had been treated at our institution from 2004 to 2011. The median time of hospitalization at our institution was 31.5 days, and 44 patients required intensive medical care. Back pain and fever were documented in 66.7 and 33.3 % of cases, respectively. The radiologic diagnosis of VO was made in 94.8 % of all obtained magnetic resonance imaging scans and in 66.2 % of all computed tomography (CT) scans. Biopsies were taken in 71 patients, and the causative organisms were identified in 56.2 % of patients, with Staphylococcus aureus being the predominant pathogen. Fifty-six patients underwent surgical treatment. During hospitalization, infectious complications were observed in 63 patients (60.0 %). The most common complications were psoas, paravertebral and epidural abscesses. Patients with S. aureus infections had a significantly higher rate of infectious complications than those without (76.5 vs. 40.3 %, respectively), and were more frequently treated in intensive care units (58.8 vs. 34.7 %, respectively). Overall in-hospital mortality rate was 12.4 %. Elevated C-reactive protein levels at admission, advanced age and a Charlson Comorbidity Index of ≥2 were associated with higher mortality. CONCLUSIONS: Magnetic resonance imaging currently is the imaging procedure of choice for the radiologic diagnosis of VO. Mortality is attributable in part to co-morbidities. However, infections with S. aureus are frequent in this patient population and are associated with a higher rate of complications and a trend towards higher mortality.

Are histopathological findings of diagnostic value in native valve endocarditis?

BACKGROUND: Optimal management of infective endocarditis (IE) depends on the early detection of IE-causing pathogens and on appropriate antimicrobial and surgical therapy. The current guidelines of the European Society of Cardiology (ESC) recommend histopathological examination as the gold standard for diagnosing IE Habib et al. (Eur Heart J 30:2369-2413, 2005). We hypothesize that histopathological findings do not provide additional information relevant to clinical decision-making. METHODS: We retrospectively reviewed a cohort of patients who had undergone surgery for native valve endocarditis (NVE) at the University Hospital Regensburg between September 1994 and February 2005. All episodes of intraoperatively confirmed endocarditis during this period were included in the study. Data were retrieved from surgical records, microbiological and histopathological reports, and medical files of the treating as well as admitting hospital. Pathogens were correlated with the site of manifestation of the affected heart valve and with clinical and histopathological findings. RESULTS: A total of 163 episodes of NVE were recorded and entered into our study for analysis. The valves affected were the aortic valve (45 %), the mitral valve (28 %), the aortic and mitral valve (22 %), and other valves (5 %). IE-causing pathogens were Staphylococcus aureus (22 %), viridans streptococci (18 %), enterococci (10 %), streptococci other than Streptococcus viridans (9 %), coagulase-negative staphylococci (5 %), miscellaneous pathogens (4 %), and culture-negative endocarditis (33 %). Infection with S. aureus was associated with high rates of sepsis, septic foci, and embolic events, while patients with enterococcal IE showed the highest rate of abscesses. Mortality rate in all subgroups was low without significant differences. However, histopathological findings correlated poorly with the pathogen involved and showed only few significant associations that were without clinical relevance. CONCLUSIONS: The clinical presentation of IE depends on the pathogen involved. Among the episodes of NVE examined, the histopathological examination of resected heart valves did not show any pathogen-specific morphological patterns and therefore did not provide any additional information of clinical value. Based on our findings, we recommend complementary cultures of the resected materials (valve tissue, thrombotic material, pacer wire) and implementation of molecular diagnostic methods (e.g., broad-range PCR amplification techniques) instead of histopathological analyses of resected valve tissue.

Pandemic and post-pandemic influenza A (H1N1) seasons in a tertiary care university hospital-high rate of complications compared to previous influenza seasons.

INTRODUCTION: The aim was to study the characteristics and case severity of patients hospitalized for influenza with a pandemic strain at a German tertiary care university hospital in 2009/10 and 2010/11 and to compare them to two previous influenza seasons. METHODS: An observational study of all patients hospitalized for laboratory-confirmed influenza during the last four influenza seasons at Regensburg University Hospital was undertaken. RESULTS: During the last four seasons, a rising number of patients were admitted due to influenza (4 in 2007/8, 16 in 2008/9, 27 in 2009/10, and 55 in 2010/11). Patients seen in the last two seasons were younger (median age 63 years in 2007/8, 52 years in 2008/9, 42 years in 2009/10, and 48 years in 2010/11) (p = 0.046) and presented with a lower rate of major comorbidities (75 % in 2007/8, 62.5 % in 2008/9, 37 % in 2009/10, and 47.3 % in 2010/11). The pandemic and post-pandemic seasons were characterized by a high rate of seriously ill patients with longer hospitalizations (11 days in 2007/8, 7 days in 2008/9, 22 days in 2009/10 and 2010/11) (p = 0.004) and higher rates of intensive care unit (ICU) admission (25 % in 2007/8, 18.8 % in 2008/9, 66.7 % in 2009/10, and 52.7 % in 2010/11) (p = 0.003) and mechanical ventilation (25 % in 2007/8, 6.3 % in 2008/9, 63 % in 2009/10, and 49.1 % in 2010/11) (p < 0.001). Extracorporeal membrane oxygenation (ECMO) was necessary in 33.3 % of patients in 2009/10 and 25.5 % in 2010/11. We had six fatalities in both pandemic and post-pandemic seasons. CONCLUSION: Compared to seasonal influenza, we observed even more so in the post-pandemic than the pandemic season a higher number of younger patients, with less serious comorbidities often showing a very severe course.

[Fever of unknown origin]. / Fieber ungeklärter Ursache.

Fever of unknown origin (FUO) is defined as sustained unexplained fever despite intensive diagnostic evaluation and represents a particular diagnostic challenge. It can be classified into different categories, e.g. classical, nosocomial, neutropenic and HIV-associated FUO, which is based on the patient-specific clinical and immunological situation. Infections, malignant diseases and non-infectious inflammatory diseases have to be considered as the most important causes of FUO; however, no definitive diagnosis can be established in a substantial number of FUO patients despite an extensive diagnostic work-up. The present review focuses on the important diagnostic aspects as well as therapeutic options in FUO patients.