Comparative Analysis of Lymphocyte Populations in Post-COVID-19 Condition and COVID-19 Convalescent Individuals.

Reduced lymphocyte counts in peripheral blood are one of the most common observations in acute phases of viral infections. Although many studies have already examined the impact of immune (dys)regulation during SARS-CoV-2 infection, there are still uncertainties about the long-term consequences for lymphocyte homeostasis. Furthermore, as persistent cellular aberrations have been described following other viral infections, patients with "Post-COVID-19 Condition" (PCC) may present similarly. In order to investigate cellular changes in the adaptive immune system, we performed a retrospective analysis of flow cytometric data from lymphocyte subpopulations in 106 patients with confirmed SARS-CoV-2 infection who received medical care at our institution. The patients were divided into three groups according to the follow-up date; laboratory analyses of COVID-19 patients were compared with 28 unexposed healthy controls. Regarding B lymphocyte subsets, levels of IgA + CD27+, IgG + CD27+, IgM + CD27- and switched B cells were significantly reduced at the last follow-up compared to unexposed healthy controls (UHC). Of the 106 COVID-19 patients, 56 were clinically classified as featuring PCC. Significant differences between PCC and COVID-19 convalescents compared to UHC were observed in T helper cells and class-switched B cells. However, we did not detect specific or long-lasting immune cellular changes in PCC compared to the non-post-COVID-19 condition.

Respiratory Syncytial Virus in Adult Patients at a Tertiary Care Hospital in Germany: Clinical Features and Molecular Epidemiology of the Fusion Protein in the Severe Respiratory Season of 2022/2023.

Following an interseasonal rise in mainly pediatric respiratory syncytial virus (RSV) cases in Germany in 2021, an exceptionally high number of adult cases was observed in the subsequent respiratory season of 2022/2023. The aim of this study was to compare the clinical presentation of RSV infections in the pre- and post-SARS-CoV-2 pandemic periods. Additionally, the local epidemiology of the RSV fusion protein was analyzed at a molecular genetic and amino acid level. RSV detections in adults peaked in calendar week 1 of 2023, 8 weeks earlier than the earliest peak observed in the three pre-pandemic seasons. Although the median age of the adult patients was not different (66.5 vs. 65 years), subtle differences between both periods regarding comorbidities and the clinical presentation of RSV cases were noted. High rates of comorbidities prevailed; however, significantly lower numbers of patients with a history of lung transplantation (p = 0.009), chronic kidney disease (p = 0.013), and immunosuppression (p = 0.038) were observed in the 2022/2023 season. In contrast, significantly more lower respiratory tract infections (p < 0.001), in particular in the form of pneumonia (p = 0.015) and exacerbations of obstructive lung diseases (p = 0.008), were detected. An ICU admission was noted for 23.7% of all patients throughout the study period. Sequence analysis of the fusion protein gene revealed a close phylogenetic relatedness, regardless of the season of origin. However, especially for RSV-B, an accumulation of amino acid point substitutions was noted, including in antigenic site Ø. The SARS-CoV-2 pandemic had a tremendous impact on the seasonality of RSV, and the introduction of new vaccination and immunization strategies against RSV warrants further epidemiologic studies of this important pathogen.

Clinical management, pathogen spectrum and outcomes in patients with pyogenic liver abscess in a German tertiary-care hospital.

Pyogenic liver abscesses (PLA) are life-threatening disorders and require immediate treatment, but structured evidence is sparse and treatment guidelines are not established. In a retrospective observational study of 221 adult PLA patients (mean age 63 years, 63% men) treated between 2013 and 2019 at the Leipzig University Medical Center, we characterized pathogen spectrum, clinical management and outcomes. Biliary malignancies (33%), cholelithiasis (23%) and ischemic biliary tract disease (16%) were most common causes of PLA. Comorbidities included malignancies (40%) and diabetes mellitus (35%). Abdominal ultrasound was the preferred initial imaging modality (58%). Enterobacterales (58%), enterococci (42%) and streptococci (18%) were identified as most frequent pathogens. 97% of patients were treated with antibiotics and 75% of patients underwent an invasive treatment procedure. The 30-day mortality was almost identical in patients with and without underlying malignancy (14.6% vs. 14.4%, p = 0.96), while the one-year outcome differed significantly (58.4% vs. 29.6%, p < 0.001). Positive blood cultures (OR 4.78, 95% CI 1.39 to 22.5, p = 0.023) and detection of Enterobacterales (OR 3.55, 95% CI 1.40 to 9.97, p = 0.010) were associated with increased 30-day-mortality. We conclude that ultrasound, extensive microbiologic diagnosis, adequate anti-infective therapy and early intervention are crucial for the management of PLA.

Metagenomic next-generation sequencing as a diagnostic tool in the clinical routine of an infectious diseases department: a retrospective cohort study.

BACKGROUND: Metagenomic next-generation sequencing (mNGS) of circulating cell-free DNA from plasma is a hypothesis-independent broadband diagnostic method for identification of potential pathogens. So far, it has only been investigated in special risk populations (e.g. patients with neutropenic fever). PURPOSE: To investigate the extent to which mNGS (DISQVER® platform) can be used in routine clinical practice. METHODS: We collected whole blood specimens for mNGS testing, blood cultures (BC), and pathogen-specific PCR diagnostics. Clinical data and pathogen diagnostics were retrospectively reviewed by an infectious disease expert panel regarding the adjustment of anti-infective therapy. RESULTS: In 55 selected patients (median age 53 years, 67% male) with heterogeneous diagnoses, a total of 66 different microorganisms and viruses were detected using mNGS (51% viruses, 38% bacteria, 8% fungi, 3% parasites). The overall positivity rate of mNGS was 53% (29/55). Fifty-two out of 66 (79%) potential pathogens detected by mNGS were found in patients with primary or secondary immunodeficiency. The concordance rates of BC and pathogen-specific PCR diagnostics with mNGS testing were 14% (4/28) and 36% (10/28), respectively (p < 0.001). An additional bacterial pathogen (Streptococcus agalactiae) could only be detected by BC. Therapeutic consequences regarding anti-infective therapy were drawn from 23 pathogens (35% of detections), with 18 of these detections occurring in patients with immunodeficiency. CONCLUSIONS: We conclude that mNGS is a useful diagnostic tool, but should only be performed selectively in addition to routine diagnostics of infectious diseases. The limited number of patients and the retrospective study design do not allow any further conclusions.

[Infectious Diseases - a new specialty for postgraduate training in Germany]. / Infektiologie ­ eine neue Facharztdisziplin in Deutschland.

Medicine in Germany is currently facing major structural and economic challenges. Infectious Diseases, with the recent introduction of a new specialty in "Internal Medicine and Infectious Diseases" and with the existing additional training for almost all specializations, will make an important contribution to overcoming these challenges. Expertise in infectious diseases has to be very broad and requires high interdisciplinarity, which makes infectious diseases an attractive and demanding specialty. The complex fundamentals of infectious diseases must now be quickly conveyed to as many physicians as possible in a short period of time, as part of their specialization or as additional training. Until this is achieved, transitional solutions will be necessary for some time. The adaptation of the current billing and reimbursement system for infectious diseases services and improved intersectoral cooperation are of the utmost importance for the further development of the specialty.

Applying Machine Learning to Blood Count Data Predicts Sepsis with ICU Admission.

BACKGROUND: Timely diagnosis is crucial for sepsis treatment. Current machine learning (ML) models suffer from high complexity and limited applicability. We therefore created an ML model using only complete blood count (CBC) diagnostics. METHODS: We collected non-intensive care unit (non-ICU) data from a German tertiary care centre (January 2014 to December 2021). Using patient age, sex, and CBC parameters (haemoglobin, platelets, mean corpuscular volume, white and red blood cells), we trained a boosted random forest, which predicts sepsis with ICU admission. Two external validations were conducted using data from another German tertiary care centre and the Medical Information Mart for Intensive Care IV database (MIMIC-IV). Using the subset of laboratory orders also including procalcitonin (PCT), an analogous model was trained with PCT as an additional feature. RESULTS: After exclusion, 1 381 358 laboratory requests (2016 from sepsis cases) were available. The CBC model shows an area under the receiver operating characteristic (AUROC) of 0.872 (95% CI, 0.857-0.887). External validations show AUROCs of 0.805 (95% CI, 0.787-0.824) for University Medicine Greifswald and 0.845 (95% CI, 0.837-0.852) for MIMIC-IV. The model including PCT revealed a significantly higher AUROC (0.857; 95% CI, 0.836-0.877) than PCT alone (0.790; 95% CI, 0.759-0.821; P < 0.001). CONCLUSIONS: Our results demonstrate that routine CBC results could significantly improve diagnosis of sepsis when combined with ML. The CBC model can facilitate early sepsis prediction in non-ICU patients with high robustness in external validations. Its implementation in clinical decision support systems has strong potential to provide an essential time advantage and increase patient safety.

Early-Outcome Differences between Acute and Chronic Periprosthetic Joint Infections-A Retrospective Single-Center Study.

Periprosthetic joint infections (PJI) are serious complications after arthroplasty, associated with high morbidity, mortality, and complex treatment processes. The outcomes of different PJI entities are largely unknown. The aim of this study was to access the early outcomes of different PJI entities. A retrospective, single-center study was conducted. The characteristics and outcomes of patients with PJI treated between 2018 and 2019 were evaluated 12 months after the completion of treatment. Primary endpoints were mortality, relapse free survival (RFS) and postoperative complications (kidney failure, sepsis, admission to ICU). A total of 115 cases were included [19.1% early (EI), 33.0% acute late (ALI), and 47.8% chronic infections (CI)]. Patients with ALI were older (p = 0.023), had higher ASA scores (p = 0.031), preoperative CRP concentrations (p = 0.011), incidence of kidney failure (p = 0.002) and sepsis (p = 0.026). They also tended towards higher in-house mortality (ALI 21.1%, 13.6% EI, 5.5% CI) and admission to ICU (ALI 50.0%, 22.7% EI, 30.9% CI). At 12 months, 15.4% of patients with EI had a relapse, compared to 38.1% in ALI and 36.4% in CI. There are differences in patient characteristics and early outcomes between PJI entities. Patients with EI have better early clinical outcomes. Patients with ALI require special attention during follow-up because they have higher occurrences of relapses and postoperative complications than patients with EI and CI.

Presence of hypervirulence-associated determinants in Klebsiella pneumoniae from hospitalised patients in Germany.

BACKGROUND: Klebsiella (K.) pneumoniae is a ubiquitous Gram-negative bacterium and a common coloniser of animals and humans. Today, K. pneumoniae is one of the most persistent nosocomial pathogens worldwide and poses a severe threat/burden to public health by causing urinary tract infections, pneumonia and bloodstream infections. Infections mainly affect immunocompromised individuals and hospitalised patients. In recent years, a new type of K. pneumoniae has emerged associated with community-acquired infections such as pyogenic liver abscess in otherwise healthy individuals and is therefore termed hypervirulent K. pneumoniae (hvKp). The aim of this study was the characterisation of K. pneumoniae isolates with properties of hypervirulence from Germany. METHODS: A set of 62 potentially hypervirulent K. pneumoniae isolates from human patients was compiled. Inclusion criteria were the presence of at least one determinant that has been previously associated with hypervirulence: (I) clinical manifestation, (II) a positive string test as a marker for hypermucoviscosity, and (III) presence of virulence associated genes rmpA and/or rmpA2 and/or magA. Phenotypic characterisation of the isolates included antimicrobial resistance testing by broth microdilution. Whole genome sequencing (WGS) was performed using Illumina® MiSeq/NextSeq to investigate the genetic repertoire such as multi-locus sequence types (ST), capsule types (K), further virulence associated genes and resistance genes of the collected isolates. For selected isolates long-read sequencing was applied and plasmid sequences with resistance and virulence determinants were compared. RESULTS: WGS analyses confirmed presence of several signature genes for hvKp. Among them, the most prevalent were the siderophore loci iuc and ybt and the capsule regulator genes rmpA and rmpA2. The most dominant ST among the hvKp isolates were ST395 capsule type K2 and ST395 capsule type K5; both have been described previously and were confirmed by our data as multidrug-resistant (MDR) isolates. ST23 capsule type K1 was the second most abundant ST in this study; this ST has been described as commonly associated with hypervirulence. In general, resistance to beta-lactams caused by the production of extended-spectrum beta-lactamases (ESBL) and carbapenemases was observed frequently in our isolates, confirming the threatening rise of MDR-hvKp strains. CONCLUSIONS: Our study results show that K. pneumoniae strains that carry several determinants of hypervirulence are present for many years in Germany. The detection of carbapenemase genes and hypervirulence associated genes on the same plasmid is highly problematic and requires intensified screening and molecular surveillance. However, the non-uniform definition of hvKp complicates their detection. Testing for hypermucoviscosity alone is not specific enough to identify hvKp. Thus, we suggest that the classification of hvKp should be applied to isolates that not only fulfil phenotypical criteria (severe clinical manifestations, hypermucoviscosity) but also (I) the presence of at least two virulence loci e.g. iuc and ybt, and (II) the presence of rmpA and/or rmpA2.

[Postexposure prophylaxis after bite of a broad-winged bat with evidence of European bat lyssavirus 1 (EBLV-1)]. / Postexpositionsprophylaxe nach Biss einer Breitflügelfledermaus mit Nachweis des Europäischen Fledermaus-Lyssavirus 1 (EBLV-1).

Germany has been considered free of terrestrial rabies since 2008 as a result of intensive vaccination and surveillance efforts but reservoirs of the lyssaviruses EBLV­1 and EBLV­2 persist in bat colonies and thus pose a potential risk of infection. We report on a patient who suffered a bat bite in an urban setting in which European bat lyssavirus 1 (EBLV-1) was detected in the euthanized bat. We performed active and passive postexposure prophylaxis (PEP). This case study illustrates the ongoing risk of rabies infection due to close bat contacts in Germany and is intended to sensitize primary care physicians to take such exposure events seriously and to perform a regular PEP including administration of rabies immunoglobulin.

[Exposures to fruit plants in Germany from 2010-2019 : Analysis of the Erfurt joint poison information center database]. / Expositionen mit Fruchtpflanzen in Deutschland im Zeitraum 2010­2019 : Auswertung der Datenbank des Gemeinsamen Giftinformationszentrums Erfurt (GGIZ).

BACKGROUND: Inquiries about fruit plants are a frequent reason for consultation with poison information centers, although it should be emphasized that there are no large systematic studies on toxicity based on exposure data. The aim of this work is to determine the risk of poisoning by fruit plants in Germany. METHODS: Retrospective study of data from the Erfurt Joint Poison Information Center on poisoning inquiries regarding fruit plants (2010-2019) with a detailed presentation of interim results, a tabular handout, plant photos as identification aids, and trend analyses. RESULTS: From 16,088 plant exposures with 16,700 plants, 214 different fruit plant species were identified. Forty-five fruit plant species (21%) turned out to be relevant (≥ 30 inquiries) and of these, 6 (2.8%) turned out to be highly relevant (≥ 300 inquiries). All relevant plants were assigned a defined risk category (RC): RC 0 (2; 4.4%), RC 1 (26; 57.8%), RC 2 (12; 26.7%), and RC 3 (5; 11.1%). Regarding the inquiries, 6% (459/7607) were related to RC 0; 47.9% (3645/7607) to RC 1; 39.3% to RC 2 (2986/7607); and 6.8% (517/7607) to RC 3. Of the inquiries, 69.5% (5284/7607) were related to young children (1 to < 6 years). Exposure outcomes for all age groups were asymptomatic in 82%, mild in 14.7%, moderate in 3%, and severe in 0.3%, with severe poisoning caused by seven plant species. Interventions were initiated in 66.8% (5079) of the inquiries. Inquiries were most frequently related to Taxus baccata, Ligustrum vulgare, Physalis alkekengi, Prunus laurocerasus, Convallaria majalis, Mahonia spec., Sambucus spec., Lonicera spec., Sorbus aucuparia, Thuja spec., Hedera helix, and Cotoneaster spec. DISCUSSION: Poisoning by fruit plants in Germany is rare. However, there is a great need for information and education.

COVID-19 treatment strategies with drugs centrally procured by the German Federal Ministry of Health in a representative tertiary care hospital: a temporal analysis.

Introduction: To ensure the fastest and earliest possible treatment, the German Federal Ministry of Health (BMG) initiated central procurement and nationwide distribution of new drugs against COVID-19. A single centre was used for a retrospective temporal analysis of this procedure. Methods: A descriptive analysis of hospitalization and treatment of COVID-19 patients with drugs centrally procured by the BMG at St. Georg Hospital, Leipzig, Germany, for the period from 1 March 2020 to 28 February 2023 was employed considering the approval status, evolving guidelines and recommendations of medical societies. Results: In total, 3,412 patients ≥18 years (54.9% men) with PCR-confirmed SARS-CoV-2 infection were admitted. The mean age was 64 years during the reporting period and 66.1/70.6 years during the first and second COVID-19 waves, respectively. 964 patients (28.2%) received COVID-19 therapy with drugs procured centrally by the BMG. Remdesivir was the most commonly used (63%). SARS-CoV-2 neutralizing monoclonal antibodies represented 23% of the therapies. Peroral antivirals (nirmatrelvir/ritonavir and molnupiravir) were used in 14% of COVID-19 patients, with molnupiravir being insignificant (five prescriptions). Conclusions: Specific therapeutic approaches were mainly based on antiviral therapy in the early phase of COVID-19 to prevent severe disease progression in vulnerable patient groups. Most drugs had not been approved at the time of central procurement; therefore, prescriptions were given on a case-by-case basis after careful risk-benefit assessments. All available neutralizing monoclonal SARS-CoV-2 antibodies lost efficacy during the pandemic due to different circulating immune escape variants. Remdesivir and nirmatrelvir/ritonavir remained effective therapies in the early phase of COVID-19.

A case for routine microbial diagnostics: Results from antimicrobial susceptibility testing in post-traumatic wound infections at a Ugandan tertiary care hospital.

The global spread of antimicrobial resistance (AMR) poses an increasing challenge for clinicians in Uganda, where microbiological diagnostics are not routinely available or accessible. The aim of this study was to determine pathogen prevalence and antibiotic resistance patterns in patients with wound infections following trauma at a national referral hospital in Kampala, Uganda. In addition, the suitability of currently used empirical treatment options in this setting was evaluated. This prospective, observational study analysed antimicrobial prescriptions, culture results and antimicrobial sensitivity testing (AST) of wound swabs and blood samples from patients with clinical signs of wound infections on the trauma ward. A total of 124 patients (n = 99, 79.8% male) with a median age of 30 years (IQR 23-39) were enrolled between October 2021 and January 2022. Wound infections were classified as nosocomial in 69% of the cases. Pathogens were isolated from 122 wound swabs, yielding 238 bacterial isolates. The most prevalent pathogens were gram-negative bacteria including Escherichia coli (n = 48, 20.2%) and Acinetobacter spp. (n = 43, 18.1%). Empiric treatment consisted of ceftriaxone and gentamicin which was administered to 67.2% (n = 78) and 62.1% (n = 72) of patients, respectively. High rates of antimicrobial resistance could be demonstrated across gram-negative and gram-positive species towards the most common empiric antibiotics. Following the AST results, over 95% (n = 111) of patients required a change of treatment. Our findings demonstrate that current empiric treatment for wound infections is missing its target in hospitalized patients in Kampala. To address the growing problem of AMR in Uganda, there is a pressing need to enhance diagnostic capacity and implement structured antimicrobial stewardship programs.

Individuals at risk for severe COVID-19 in whom ritonavir-containing therapies are contraindicated or may lead to interactions with concomitant medications: a retrospective analysis of German health insurance claims data.

Background: Nirmatrelvir/ritonavir is authorized for the treatment of COVID-19 but has several contraindications and potential drug-drug interactions (pDDIs) due to ritonavir-induced irreversible inhibition of cytochrome P450 3A4. We aimed to assess the prevalence of individuals with one or more risk factors for severe COVID-19 along with contraindications and pDDIs due to ritonavir-containing COVID-19 therapy. Methods: Retrospective observational study of individuals with one or more risk factors according to Robert Koch Institute criteria for severe COVID-19 according to German statutory health insurance (SHI) claims data from the pre-pandemic years 2018-2019 based on the German Analysis Database for Evaluation and Health Services Research. Prevalence was extrapolated to the entire SHI population using age-adjusted and sex-adjusted multiplication factors. Results: Nearly 2.5 million fully insured adults, representing 61 million people in the German SHI population, were included in the analysis. In 2019, prevalence of individuals that would have been at risk of severe COVID-19 was 56.4%. Amongst them, the prevalence of contraindications for treatment with ritonavir-containing COVID-19 therapy was approximately 2% according to presence of somatic comorbidities (severe liver or kidney disease). Prevalence of intake of medicines contraindicated for their potential interactions with ritonavir-containing COVID-19 therapy was 16.5% according to Summary of Product Characteristics and 31.8% according to previously published data. The prevalence of individuals at risk of pDDIs during ritonavir-containing COVID-19 therapy without adjustment of their concomitant therapy was 56.0% and 44.3%, respectively. Prevalence data for 2018 were similar. Conclusion: Administering ritonavir-containing COVID-19 therapy can be challenging as thorough medical record review and close monitoring are required. In some cases, ritonavir-containing treatment may not be appropriate due to contraindications, risk of pDDIs, or both. For those individuals, an alternative ritonavir-free treatment should be considered.

SARS-CoV-2 Vaccine Breakthrough Infections of Omicron and Delta Variants in Healthcare Workers.

Understanding SARS-CoV-2 breakthrough infections in vaccinated healthcare workers is of key importance in mitigating the effects of the COVID-19 pandemic in healthcare facilities. An observational prospective cohort study was conducted in vaccinated employees with acute SARS-CoV-2 infection between October 2021 and February 2022. Serological and molecular testing was performed to determine SARS-CoV-2 viral load, lineage, antibody levels, and neutralizing antibody titers. A total of 571 (9.7%) employees experienced SARS-CoV-2 breakthrough infections during the enrolment period, of which 81 were included. The majority (n = 79, 97.5%) were symptomatic and most (n = 75, 92.6%) showed Ct values < 30 in RT-PCR assays. Twenty-four (30%) remained PCR-positive for > 15 days. Neutralizing antibody titers were strongest for the wildtype, intermediate for Delta, and lowest for Omicron variants. Omicron infections occurred at higher anti-RBD-IgG serum levels (p = 0.00001) and showed a trend for higher viral loads (p = 0.14, median Ct difference 4.3, 95% CI [-2.5-10.5]). For both variants, viral loads were significantly higher in participants with lower anti-RBD-IgG serum levels (p = 0.02). In conclusion, while the clinical course of infection with both the Omicron and Delta variants was predominantly mild to moderate in our study population, waning immune response over time and prolonged viral shedding were observed.

Carbapenemase-producing Gram-negative bacteria in hospital wastewater, wastewater treatment plants and surface waters in a metropolitan area in Germany, 2020.

Carbapenemase-producing bacteria (CPB) such as Klebsiella pneumoniae and Escherichia coli are causing hospital outbreaks worldwide. An important transfer route into the aquatic environment is the urban water cycle. We aimed to determine the presence of CPB in hospital wastewater, wastewater treatment plants (WWTPs) and surface waters in a German metropolitan area and to characterise these bacteria by whole-genome comparisons. During two periods in 2020, 366 samples were collected and cultivated on chromogenic screening media. Bacterial colonies were selected for species identification and PCR-based carbapenemase gene screening. Genomes of all detected CPB were sequenced and analysed for resistance gene content, followed by multilocus sequence typing (MLST) and core genome MLST (cgMLST) for K. pneumoniae and E. coli isolates. Carbapenemase genes were detected in 243 isolates, most of which belonged to genera/species Citrobacter spp. (n = 70), Klebsiella spp. (n = 57), Enterobacter spp. (n = 52) and E. coli (n = 42). Genes encoding KPC-2 carbapenemase were detected in 124 of 243 isolates. K. pneumoniae produced mainly KPC-2 and OXA-232 whereas E. coli harboured various enzymes (KPC-2, VIM-1, OXA-48, NDM-5, KPC-2 + OXA-232, GES-5, GES-5 + VIM-1, IMP-8 + OXA-48). Eight and twelve sequence types (STs) were identified for K. pneumoniae and E. coli, respectively, forming different clusters. The detection of numerous CPB species in hospital wastewater, WWTPs and river water is of concern. Genome data highlight a hospital-specific presence of distinct carbapenemase-producing K. pneumoniae and E. coli strains belonging to "global epidemic clones" in wastewater samples representing local epidemiology. The various detected CPB species including E. coli ST635, which is not known to cause human infections, could serve as reservoirs/vectors for the spread of carbapenemase genes in the environment. Therefore, effective pretreatment of hospital wastewater prior to discharge into the municipal wastewater system may be required, although swimming lakes do not appear to be a relevant risk factor for CPB ingestion and infection.

[Clostridioides difficile - New Insights and Therapy Recommendations]. / Clostridioides difficile ­ Neue Erkenntnisse und Therapieempfehlungen.

After an increase in Clostridioides difficile infections (CDI) until 2013 due to epidemic ribotypes such as 027 and 078, CDI incidence in Germany is now declining, as confirmed by recent epidemiological data. Despite this success through antimicrobial stewardship and hospital hygiene, the burden of disease remains high, especially in older patients (>65 years) with comorbidities. The main risk factor for CDI is the use of broad-spectrum antibiotics, which disrupt the gut microbiota, allowing C. difficile colonization. Coinfection with other intestinal pathogens such as enterococci can further increase the virulence of C. difficile. The updated 2021 ESCMID guidelines recommend fidaxomicin instead of vancomycin as the antibiotic of choice for the treatment of CDI because of its lower recurrence rate. Vancomycin remains a good alternative; however, metronidazole should only be used if neither antibiotic is available. In the future, ridinilazole may be available as another therapeutic option that has a narrow spectrum of activity and low intestinal absorption. For the treatment of recurrent CDI, the new guidelines also include the use of the monoclonal antibody bezlotoxumab. In addition, a new oral microbiome therapy, SER-109 (capsules containing purified Firmicutes spores), which showed promising results in a phase 3 study, may provide an easy-to-administer alternative to fecal microbiota transplantation. Hopes for a well-performing toxoid vaccine for primary and secondary prevention of CDI have unfortunately not been fulfilled in the CLOVER trial.

Chylothorax due to hepatic alveolar echinococcosis with infiltration of diaphragm and left pleura: a case report.

BACKGROUND: Alveolar echinococcosis (AE) is an endemic parasitic zoonosis in Germany. In most cases, the liver is the primary organ affected. CASE PRESENTATION: A 59-year old female patient presented with increasing exertional dyspnea and unintentional weight loss. A computed tomography (CT) scan showed a left-sided chylous pleural effusion and multiple intrahepatic masses with infiltration of the diaphragm and the pleura. The findings were initially misinterpreted as hepatocellular carcinoma (HCC) with infiltrating growth. Liver biopsy of one of the masses showed no evidence of malignancy, but an amorphous necrosis of unclear origin. HCC was further ruled out by magnetic resonance imaging (MRI). However, MRI findings were highly suspicious for hepatothoracic dissemination and complications due to AE. Typical histologic findings in a repeated and more specific examination of the liver tissue and a positive serology for echinococcosis confirmed the diagnosis of AE. As the hepatic and pulmonary manifestations were considered inoperable in a curative matter, an anti-parasitic treatment with albendazole was initiated. A video-assisted thoracoscopic surgery (VATS) with removal of the chylous effusion as well as a talc pleurodesis was performed to relieve the patient from dyspnea. Two months later, the patient was asymptomatic and a positron emission tomography (PET)-CT-scan with [18 F] fluoro-2-deoxy-d-glucose (FDG) showed a remarkable diminution of the hepatic manifestation. CONCLUSIONS: This case demonstrates a rare presentation of alveolar echinococcosis with a focus on pulmonary symptoms, emphasizing the importance of evaluation for pulmonary involvement in patients with AE and respiratory symptoms.

Epidemiology of Clostridioides difficile Infections in Germany, 2010-2019: A Review from Four Public Databases.

INTRODUCTION: Clostridioides difficile infection (CDI) is a recognized global threat especially for vulnerable populations. It is of particular concern to healthcare providers as it is found in both hospital and community settings, with severe courses, frequent recurrence, high mortality and substantial financial impact on the healthcare system. The CDI burden in Germany has been described and compared by analysing data from four different public databases. METHODS: Data on hospital burden of CDI have been extracted, compared, and discussed from four public databases for the years 2010-2019. Hospital days due to CDI were compared to established vaccine preventable diseases, such as influenza and herpes zoster, and also to CDI hospitalisations in the United States (US). RESULTS: All four databases reported comparable incidences and trends. Beginning in 2010, population-based hospitalised CDI incidence increased to a peak of > 137/100,000 in 2013. Then, incidence declined to 81/100,000 in 2019. Hospitalised patients with CDI were predominantly > 50 years of age. The population-based incidence of severe CDI was between 1.4 and 8.4/100,000 per year. Recurrence rates were between 5.9 to 6.5%. More than 1,000 CDI deaths occurred each year, with a peak of 2,666 deaths in 2015. Cumulative CDI patient days (PD) were between 204,596 and 355,466 each year, which exceeded cumulated PD for influenza and herpes zoster in most years, though year-to-year differences were observed. Finally, hospitalized CDI incidence was higher in Germany than in the US, where the disease is well recognized as a public health threat. CONCLUSIONS: All four public sources documented a decline in CDI cases since 2013, but the disease burden remains substantial and warrants continued attention as a severe public health challenge.