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1.
Z Gastroenterol ; 62(7): 1032-1041, 2024 Jul.
Artículo en Alemán | MEDLINE | ID: mdl-38976982

RESUMEN

INTRODUCTION: Clostridioides difficile infection (CDI), as a nosocomial disease, is associated with high morbidity and mortality. Even though the incidence of CDI has been declining in Germany in recent years, the individual infection may pose a medical challenge despite therapeutic advances. The aim here is to clarify which gaps practitioners consider to be particularly serious in care and in the existing evidence base. METHODS: In a moderated workshop of German CDI experts the topics considered as relevant were identified. A survey already conducted in five other countries (Australia, France, Great Britain, Canada, and Italy) was adapted and processed by 27 practitioners. During the evaluation, the topics perceived as particularly important were identified, the statements of the specialist groups were compared and changes in opinion were considered. RESULTS: 27 fully completed questionnaires were evaluated. The need for improvement was primarily seen in the prevention of CDI recurrences (74.1%) and the treatment of recurrences (55.6%). Evidence deficits were noted in the treatment of recurrences (55.6%) and identification of risk factors for recurrences (48.1%). Improving care via fecal microbiota transfer (FMT) was named by 70.4%. For guidelines, more clarity (48.1%) and more regular updates (40.7%) were desired. For patients, better education on appropriate antibiotic use (52.0%) and choice of FMT were desired (48.1%). SUMMARY: The German expert view and the international assessment is similar, when asked about the need for improvement in care and evidence gaps in the treatment of patients with CDI: The focus is on prevention and therapy of recurrent CDI. The problem of access to FMT is a German peculiarity that seems to need improvement.


Asunto(s)
Infecciones por Clostridium , Humanos , Infecciones por Clostridium/terapia , Infecciones por Clostridium/epidemiología , Alemania , Mejoramiento de la Calidad , Internacionalidad , Testimonio de Experto , Trasplante de Microbiota Fecal , Medicina Basada en la Evidencia , Evaluación de Necesidades , Infección Hospitalaria/prevención & control , Infección Hospitalaria/epidemiología , Infección Hospitalaria/terapia , Guías de Práctica Clínica como Asunto
3.
J Infect ; 89(2): 106220, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38960103

RESUMEN

OBJECTIVES: Efficacy and safety of letermovir as prophylaxis for clinically significant cytomegalovirus infections (csCVMi) was evaluated in randomised controlled trials while most of the real-world studies are single-centre experiences. METHODS: We performed a retrospective, multi-centre case-control study at six German university hospitals to evaluate clinical experiences in patients receiving CMV prophylaxis with letermovir (n = 200) compared to controls without CMV prophylaxis (n = 200) during a 48-week follow-up period after allogeneic hematopoietic cell transplantation (aHCT). RESULTS: The incidence of csCMVi after aHCT was significantly reduced in the letermovir (34%, n = 68) compared to the control group (56%, n = 112; p < 0.001). Letermovir as CMV prophylaxis (OR 0.362) was found to be the only independent variable associated with the prevention of csCMVi. Patients receiving letermovir showed significantly better survival compared to the control group (HR = 1.735, 95% CI: 1.111-2.712; p = 0.014). Of all csCMVi, 46% (n = 31) occurred after discontinuation of letermovir prophylaxis. Severe neutropenia (<500 neutrophils/µL) on the day of the stem cell infusion was the only independent variable for an increased risk of csCMVi after the end of letermovir prophylaxis. CONCLUSIONS: Our study highlights the preventive effects of letermovir on csCMVi after aHCT. A substantial proportion of patients developed a csCMVi after discontinuation of letermovir. In particular, patients with severe neutropenia require specific attention after drug discontinuation.


Asunto(s)
Acetatos , Antivirales , Infecciones por Citomegalovirus , Trasplante de Células Madre Hematopoyéticas , Quinazolinas , Humanos , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Masculino , Infecciones por Citomegalovirus/prevención & control , Femenino , Persona de Mediana Edad , Quinazolinas/uso terapéutico , Estudios Retrospectivos , Antivirales/uso terapéutico , Adulto , Acetatos/uso terapéutico , Acetatos/administración & dosificación , Estudios de Casos y Controles , Anciano , Trasplante Homólogo/efectos adversos , Adulto Joven , Citomegalovirus , Adolescente , Alemania/epidemiología , Incidencia
4.
Sci Rep ; 14(1): 13607, 2024 06 13.
Artículo en Inglés | MEDLINE | ID: mdl-38871878

RESUMEN

Fair allocation of funding in multi-centre clinical studies is challenging. Models commonly used in Germany - the case fees ("fixed-rate model", FRM) and up-front staffing and consumables ("up-front allocation model", UFAM) lack transparency and fail to suitably accommodate variations in centre performance. We developed a performance-based reimbursement model (PBRM) with automated calculation of conducted activities and applied it to the cohorts of the National Pandemic Cohort Network (NAPKON) within the Network of University Medicine (NUM). The study protocol activities, which were derived from data management systems, underwent validation through standardized quality checks by multiple stakeholders. The PBRM output (first funding period) was compared among centres and cohorts, and the cost-efficiency of the models was evaluated. Cases per centre varied from one to 164. The mean case reimbursement differed among the cohorts (1173.21€ [95% CI 645.68-1700.73] to 3863.43€ [95% CI 1468.89-6257.96]) and centres and mostly fell short of the expected amount. Model comparisons revealed higher cost-efficiency of the PBRM compared to FRM and UFAM, especially for low recruitment outliers. In conclusion, we have developed a reimbursement model that is transparent, accurate, and flexible. In multi-centre collaborations where heterogeneity between centres is expected, a PBRM could be used as a model to address performance discrepancies.Trial registration: https://clinicaltrials.gov/ct2/show/NCT04768998 ; https://clinicaltrials.gov/ct2/show/NCT04747366 ; https://clinicaltrials.gov/ct2/show/NCT04679584 .


Asunto(s)
Análisis Costo-Beneficio , Humanos , Alemania , Mecanismo de Reembolso , Estudios de Cohortes , COVID-19/epidemiología , COVID-19/economía
5.
Sci Rep ; 14(1): 13295, 2024 06 10.
Artículo en Inglés | MEDLINE | ID: mdl-38858499

RESUMEN

Non-tuberculous mycobacterial pulmonary disease (NTM-PD) is considered a growing health concern. The majority of NTM-PD cases in Europe are caused by slow-growing mycobacteria (SGM). However, distinct radiological features of different SGM remain largely uninvestigated. We applied a previously described radiological score to a patient cohort consisting of individuals with isolation of different SGM. Correlations between clinical data, species and computed tomography (CT) features were examined by logistic and linear regression analyses, as well as over the course of time. Overall, 135 pulmonary CT scans from 84 patients were included. The isolated NTM-species were mainly Mycobacterium avium complex (MAC, n = 49), as well as 35 patients with non-MAC-species. Patients with isolation of M. intracellulare had more extensive CT findings compared to all other SGM species (coefficient 3.53, 95% Cl - 0.37 to 7.52, p = 0.075) while patients meeting the ATS criteria and not undergoing therapy exhibited an increase in CT scores over time. This study provides insights into differential radiological features of slow-growing NTM. While M. intracellulare exhibited a tendency towards higher overall CT scores, the radiological features were similar across different SGM. The applied CT score might be a useful instrument for monitoring patients and could help to guide antimycobacterial therapy.


Asunto(s)
Infecciones por Mycobacterium no Tuberculosas , Micobacterias no Tuberculosas , Tomografía Computarizada por Rayos X , Humanos , Masculino , Femenino , Infecciones por Mycobacterium no Tuberculosas/diagnóstico por imagen , Infecciones por Mycobacterium no Tuberculosas/microbiología , Tomografía Computarizada por Rayos X/métodos , Anciano , Persona de Mediana Edad , Micobacterias no Tuberculosas/aislamiento & purificación , Micobacterias no Tuberculosas/crecimiento & desarrollo , Complejo Mycobacterium avium/aislamiento & purificación , Pulmón/microbiología , Pulmón/diagnóstico por imagen , Estudios Retrospectivos , Adulto , Infección por Mycobacterium avium-intracellulare/diagnóstico por imagen , Infección por Mycobacterium avium-intracellulare/microbiología
6.
J Neuroimmune Pharmacol ; 19(1): 26, 2024 May 31.
Artículo en Inglés | MEDLINE | ID: mdl-38819756

RESUMEN

BACKGROUND: The composition of gut microbiota plays a pivotal role in priming the immune system and thus impacts autoimmune diseases. Data on the effects of gut bacteria eradication via systemic antibiotics on immune neuropathies are currently lacking. This study therefore assessed the effects of antibiotics-induced gut microbiota alterations on the severity of experimental autoimmune neuritis (EAN), a rat model of Guillain-Barré Syndrome (GBS). Myelin P0 peptide 180-199 (P0 180-199)-induced EAN severity was compared between adult Lewis rats (12 weeks old) that received drinking water with or without antibiotics (colistin, metronidazole, vancomycin) and healthy rats, beginning antibiotics treatment immediately after immunization (day 0), and continuing treatment for 14 consecutive days. Neuropathy severity was assessed via a modified clinical score, and then related to gut microbiota alterations observed after fecal 16S rRNA gene sequencing at baseline and after EAN induction. Effectors of gut mucosal and endoneurial immunity were assessed via immunostaining. EAN rats showed increased gut mucosal permeability alongside increased mucosal CD8+ T cells compared to healthy controls. Antibiotics treatment alleviated clinical EAN severity and reduced endoneurial T cell infiltration, decreased gut mucosal CD8+ T cells and increased gut bacteria that may be associated with anti-inflammatory mechanisms, like Lactobacillus or Parasutterella. Our findings point out a relation between gut mucosal immunity and the pathogenesis of EAN, and indicate that antibiotics-induced intestinal immunomodulation might be a therapeutic approach to alleviate autoimmunity in immune neuropathies. Further studies are warranted to evaluate the clinical transferability of these findings to patients with GBS.


Asunto(s)
Antibacterianos , Microbioma Gastrointestinal , Inmunomodulación , Neuritis Autoinmune Experimental , Ratas Endogámicas Lew , Animales , Neuritis Autoinmune Experimental/inmunología , Neuritis Autoinmune Experimental/tratamiento farmacológico , Ratas , Microbioma Gastrointestinal/efectos de los fármacos , Antibacterianos/farmacología , Inmunomodulación/efectos de los fármacos , Masculino
7.
Infection ; 2024 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-38700656

RESUMEN

PURPOSE: The influence of new SARS-CoV-2 variants on the post-COVID-19 condition (PCC) remains unanswered. Therefore, we examined the prevalence and predictors of PCC-related symptoms in patients infected with the SARS-CoV-2 variants delta or omicron. METHODS: We compared prevalences and risk factors of acute and PCC-related symptoms three months after primary infection (3MFU) between delta- and omicron-infected patients from the Cross-Sectoral Platform of the German National Pandemic Cohort Network. Health-related quality of life (HrQoL) was determined by the EQ-5D-5L index score and trend groups were calculated to describe changes of HrQoL between different time points. RESULTS: We considered 758 patients for our analysis (delta: n = 341; omicron: n = 417). Compared with omicron patients, delta patients had a similar prevalence of PCC at the 3MFU (p = 0.354), whereby fatigue occurred most frequently (n = 256, 34%). HrQoL was comparable between the groups with the lowest EQ-5D-5L index score (0.75, 95% CI 0.73-0.78) at disease onset. While most patients (69%, n = 348) never showed a declined HrQoL, it deteriorated substantially in 37 patients (7%) from the acute phase to the 3MFU of which 27 were infected with omicron. CONCLUSION: With quality-controlled data from a multicenter cohort, we showed that PCC is an equally common challenge for patients infected with the SARS-CoV-2 variants delta and omicron at least for the German population. Developing the EQ-5D-5L index score trend groups showed that over two thirds of patients did not experience any restrictions in their HrQoL due to or after the SARS-CoV-2 infection at the 3MFU. CLINICAL TRAIL REGISTRATION: The cohort is registered at ClinicalTrials.gov since February 24, 2021 (Identifier: NCT04768998).

8.
Sci Rep ; 14(1): 12365, 2024 05 29.
Artículo en Inglés | MEDLINE | ID: mdl-38811590

RESUMEN

SARS-CoV-2 is the causative agent of COVID-19. Timely and accurate diagnostic testing is vital to contain the spread of infection, reduce delays in treatment and care, and inform patient management. Optimal specimen type (e.g. nasal swabs or saliva), timing of sampling, viral marker assayed (RNA or antigen), and correlation with viral infectivity and COVID-19 symptoms severity remain incompletely defined. We conducted a field study to evaluate SARS-CoV-2 viral marker kinetics starting from very early times after infection. We measured RNA and antigen levels in nasal swabs and saliva, virus outgrowth in cell culture from nasal swabs, and antibody levels in blood in a cohort of 30 households. Nine household contacts (HHC) became infected with SARS-CoV-2 during the study. Viral RNA was detected in saliva specimens approximately 1-2 days before nasal swabs in six HHC. Detection of RNA was more sensitive than of antigen, but antigen detection was better correlated with culture positivity, a proxy for contagiousness. Anti-nucleocapsid antibodies peaked one to three weeks post-infection. Viral RNA and antigen levels were higher in specimens yielding replication competent virus in cell culture. This study provides important data that can inform how to optimally interpret SARS-CoV-2 diagnostic test results.


Asunto(s)
Anticuerpos Antivirales , Biomarcadores , COVID-19 , Composición Familiar , ARN Viral , SARS-CoV-2 , Saliva , Humanos , COVID-19/diagnóstico , COVID-19/transmisión , COVID-19/virología , SARS-CoV-2/aislamiento & purificación , SARS-CoV-2/inmunología , Saliva/virología , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , Femenino , Antígenos Virales/análisis , Antígenos Virales/inmunología , Cinética , Masculino , Adulto , Persona de Mediana Edad
9.
J Infect Public Health ; 17(4): 642-649, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38458134

RESUMEN

BACKGROUND: Vulnerability to infectious diseases in refugees is dependent on country of origin, flight routes, and conditions. Information on specific medical needs of different groups of refugees is lacking. We assessed the prevalence of infectious diseases, immunity to vaccine-preventable diseases, and chronic medical conditions in children, adolescents, and adult refugees from Ukraine who arrived in Germany in 2022. METHODS: Using different media, we recruited Ukrainian refugees at 13 sites between 9-12/2022. An antigen test for acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection, serologies for a range of vaccine-preventable diseases, as well as interferon gamma release assays (IGRAs) for tuberculosis (TB), and SARS-CoV-2 were performed. We assessed personal and family history of chronic medical conditions, infectious diseases, vaccination status, and conditions during migration. RESULTS: Overall, 1793 refugees (1401 adults and 392 children/adolescents) were included. Most participants were females (n = 1307; 72·3%) and from Eastern or Southern Ukraine. TB IGRA was positive in 13% (n = 184) of the adults and in 2% (n = 7) of the children. Serology-based immunological response was insufficient in approximately 21% (360/1793) of the participants for measles, 32% (572/1793) for diphtheria, and 74% (1289/1793) for hepatitis B. CONCLUSIONS: We show evidence of low serological response to vaccine-preventable infections and increased LTBI prevalence in Ukrainian refugees. These findings should be integrated into guidelines for screening and treatment of infectious diseases in migrants and refugees in Germany and Europe. Furthermore, low immunity for vaccine-preventable diseases in Ukrainians independent of their refugee status, calls for tailor-made communication efforts.


Asunto(s)
Enfermedades Transmisibles , Pueblos de Europa Oriental , Refugiados , Tuberculosis , Enfermedades Prevenibles por Vacunación , Adolescente , Adulto , Niño , Femenino , Humanos , Masculino , Enfermedades Transmisibles/epidemiología , Estudios Transversales , Alemania/epidemiología , Prevalencia , Tuberculosis/epidemiología , Tuberculosis/prevención & control , Universidades
10.
JAC Antimicrob Resist ; 6(2): dlae039, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38486662

RESUMEN

Background: Antimicrobial stewardship (AMS) programmes are established across the world to treat infections efficiently, prioritize patient safety, and reduce the emergence of antimicrobial resistance. One of the core elements of AMS programmes is guidance to support and direct physicians in making efficient, safe and optimal decisions when prescribing antibiotics. To optimize and tailor AMS, we need a better understanding of prescribing physicians' experience with AMS guidance. Objectives: To explore the prescribing physicians' user experience, needs and targeted improvements of AMS guidance in hospital settings. Methods: Semi-structured interviews were conducted with 36 prescribing physicians/AMS guidance users from hospital settings in Canada, Germany, Israel, Latvia, Norway and Sweden as a part of the international PILGRIM trial. A socioecological model was applied as an overarching conceptual framework for the study. Results: Research participants were seeking more AMS guidance than is currently available to them. The most important aspects and targets for improvement of AMS guidance were: (i) quality of guidelines; (ii) availability of infectious diseases specialists; and (iii) suitability of AMS guidance to department context. Conclusions: Achieving prudent antibiotic use not only depends on individual and collective levels of commitment to follow AMS guidance but also on the quality, availability and suitability of the guidance itself. More substantial commitment from stakeholders is needed to allocate the required resources for delivering high-quality, available and relevant AMS guidance to make sure that the prescribers' AMS needs are met.

11.
Front Med (Lausanne) ; 11: 1332716, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38510457

RESUMEN

Objectives: To investigate, whether inflammatory rheumatic diseases (IRD) inpatients are at higher risk to develop a severe course of SARS-CoV-2 infections compared to the general population, data from the German COVID-19 registry for IRD patients and data from the Lean European Survey on SARS-CoV-2 (LEOSS) infected patients covering inpatients from the general population with SARS-CoV-2 infections were compared. Methods: 4310 (LEOSS registry) and 1139 cases (IRD registry) were collected in general. Data were matched for age and gender. From both registries, 732 matched inpatients (LEOSS registry: n = 366 and IRD registry: n = 366) were included for analyses in total. Results: Regarding the COVID-19 associated lethality, no significant difference between both registries was observed. Age > 65°years, chronic obstructive pulmonary disease, diabetes mellitus, rheumatoid arthritis, spondyloarthritis and the use of rituximab were associated with more severe courses of COVID-19. Female gender and the use of tumor necrosis factor-alpha inhibitors (TNF-I) were associated with a better outcome of COVID-19. Conclusion: Inflammatory rheumatic diseases (IRD) patients have the same risk factors for severe COVID-19 regarding comorbidities compared to the general population without any immune-mediated disease or immunomodulation. The use of rituximab was associated with an increased risk for severe COVID-19. On the other hand, the use of TNF-I was associated with less severe COVID-19 compared to the general population, which might indicate a protective effect of TNF-I against severe COVID-19 disease.

12.
Int J Infect Dis ; 143: 107017, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38521450

RESUMEN

Yellow fever (YF) is a potentially lethal viral hemorrhagic fever that can be prevented with the 17D live attenuated YF vaccine. However, this vaccination can cause severe adverse reactions including vaccine-associated YF. Here, we describe the case of a 32-year-old female who was permanently immunosuppressed with an anti-CD20 antibody due to multiple sclerosis. Following YF vaccination, the patient developed a variety of symptoms such as febrile temperatures, muscle and joint pain, headaches, and dysuria. A vaccine-associated YF with viremia was diagnosed. To avoid a potentially severe course of the disease, sofosbuvir was used as antiviral treatment followed by the resolution of symptoms and serological response. As travelers with chronic diseases and immunosuppression will increasingly engage in long distance travel, this case demonstrates the importance of assessing patient history prior to the administration of live vaccines and points towards a possible therapeutic approach in those suffering from vaccine-associated YF.


Asunto(s)
Antivirales , Huésped Inmunocomprometido , Sofosbuvir , Vacuna contra la Fiebre Amarilla , Fiebre Amarilla , Adulto , Femenino , Humanos , Antivirales/uso terapéutico , Antivirales/efectos adversos , Rituximab/efectos adversos , Rituximab/uso terapéutico , Sofosbuvir/uso terapéutico , Sofosbuvir/efectos adversos , Fiebre Amarilla/inmunología , Vacuna contra la Fiebre Amarilla/efectos adversos , Vacuna contra la Fiebre Amarilla/inmunología , Antígenos CD20/inmunología , Antígenos CD20/uso terapéutico , Esclerosis Múltiple/inmunología , Esclerosis Múltiple/terapia
13.
Dtsch Med Wochenschr ; 149(9): 533-536, 2024 Apr.
Artículo en Alemán | MEDLINE | ID: mdl-38499041

RESUMEN

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.


Asunto(s)
Enfermedades Transmisibles , Médicos , Humanos , Enfermedades Transmisibles/terapia , Alemania , Educación de Postgrado en Medicina , Medicina Interna/educación , Especialización
14.
Biologicals ; 85: 101746, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38309984

RESUMEN

Within the Innovative Health Initiative (IHI) Inno4Vac CHIMICHURRI project, a regulatory workshop was organised on the development and manufacture of challenge agent strains for Controlled Human Infection Model (CHIM) studies. Developers are often uncertain about which GMP requirements or regulatory guidelines apply but should be guided by the 2022 technical white paper "Considerations on the Principles of Development and Manufacturing Qualities of Challenge Agents for Use in Human Infection Models" (published by hVIVO, Wellcome Trust, HIC-Vac consortium members). Where those recommendations cannot be met, regulators advise following the "Principles of GMP" until definitive guidelines are available. Sourcing wild-type virus isolates is a significant challenge for developers. Still, it is preferred over reverse genetics challenge strains for several reasons, including implications and regulations around genetically modified organisms (GMOs). Official informed consent guidelines for collecting isolates are needed, and the characterisation of these isolates still presents risks and uncertainty. Workshop topics included ethics, liability, standardised clinical endpoints, selection criteria, sharing of challenge agents, and addressing population heterogeneity concerning vaccine response and clinical course. The organisers are confident that the workshop discussions will contribute to advancing ethical, safe, and high-quality CHIM studies of influenza, RSV and C. difficile, including adequate regulatory frameworks.


Asunto(s)
Clostridioides difficile , Vacunas contra la Influenza , Gripe Humana , Virus , Humanos , Gripe Humana/prevención & control , Virus/genética
15.
Infection ; 52(3): 1159-1163, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38296936

RESUMEN

PURPOSE: Antistaphylococcal penicillins and cefazolin have been used as first line therapy in Methicillin-susceptible Staphylococcus aureus bloodstream infection. While efficacy of both regimens seems to be similar, the compounds may differ with regard to tolerability. This study aims to describe the clinical use of cefazolin and flucloxacillin, focussing on discontinuation or change of anti-infective agent due to adverse events. METHODS: This observational prospective study was conducted at two German tertiary care centres with an internal recommendation of flucloxacillin for MSSA-BSI in one, and of cefazolin in the other centre. Adverse events were registered weekly under treatment and at a 90-day follow-up. Descriptive analysis was complemented by a propensity score analysis comparing adverse events (stratified rank-based test applied to the sum of Common Terminology Criteria for adverse events ratings per patient). RESULTS: Of 71 patients included, therapy was initiated with flucloxacillin in 56 (79%), and with cefazolin in 15 (21%). The propensity score analysis indicates a statistically significant difference concerning the severity of adverse events between the treatment groups in favour of cefazolin (p = 0.019). Adverse events led to discontinuation of flucloxacillin in 7 individuals (13% of all patients receiving flucloxacillin). Clinical outcome was not different among treatment groups. CONCLUSION: Using cefazolin rather than flucloxacillin as a first line agent for treatment of MSSA-BSI is supported by these clinical data.


Asunto(s)
Antibacterianos , Cefazolina , Floxacilina , Infecciones Estafilocócicas , Staphylococcus aureus , Humanos , Cefazolina/uso terapéutico , Floxacilina/uso terapéutico , Masculino , Femenino , Infecciones Estafilocócicas/tratamiento farmacológico , Infecciones Estafilocócicas/microbiología , Persona de Mediana Edad , Estudios Prospectivos , Antibacterianos/uso terapéutico , Antibacterianos/efectos adversos , Anciano , Staphylococcus aureus/efectos de los fármacos , Bacteriemia/tratamiento farmacológico , Bacteriemia/microbiología , Adulto , Anciano de 80 o más Años , Alemania
16.
Z Gastroenterol ; 62(4): 490-499, 2024 Apr.
Artículo en Alemán | MEDLINE | ID: mdl-37187187

RESUMEN

INTRODUCTION: Fecal microbiota transfer (FMT) is a treatment to modulate the gastrointestinal microbiota. Its use in recurrent Clostridioides difficile infection (rCDI) is established throughout Europe and recommended in national and international guidelines. In Germany, the FMT is codeable in the hospital reimbursement system. A comprehensive survey on the frequency of use based on this coding is missing so far. MATERIAL AND METHODOLOGY: Reports of the Institute for Hospital Remuneration (InEK), the Federal Statistical Office (DESTATIS), and hospital quality reports 2015-2021 were examined for FMT coding and evaluated in a structured expert consultation. RESULTS: Between 2015 and 2021, 1,645 FMT procedures were coded by 175 hospitals. From 2016 to 2018, this was a median of 293 (274-313) FMT annually, followed by a steady decline in subsequent years to 119 FMT in 2021. Patients with FMT were 57.7% female, median age 74 years, and FMT was applied colonoscopically in 72.2%. CDI was the primary diagnosis in 86.8% of cases, followed by ulcerative colitis in 7.6%. DISCUSSION: In Germany, FMT is used less frequently than in the European comparison. One application hurdle is the regulatory classification of FMT as a non-approved drug, which leads to significantly higher costs in manufacturing and administration and makes reimbursement difficult. The European Commission recently proposed a regulation to classify FMT as a transplant. This could prospectively change the regulatory situation of FMT in Germany and thus contribute to a nationwide offer of a therapeutic procedure recommended in guidelines.


Asunto(s)
Clostridioides difficile , Infecciones por Clostridium , Microbioma Gastrointestinal , Humanos , Femenino , Anciano , Masculino , Trasplante de Microbiota Fecal/métodos , Infecciones por Clostridium/terapia , Alemania/epidemiología , Resultado del Tratamiento , Recurrencia
17.
Leukemia ; 38(1): 168-180, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-38049509

RESUMEN

Patients with multiple myeloma (MM) routinely receive mRNA-based vaccines to reduce COVID-19-related mortality. However, whether disease- and therapy-related alterations in immune cells and cytokine-responsiveness contribute to the observed heterogeneous vaccination responses is unclear. Thus, we analyzed peripheral blood mononuclear cells from patients with MM during and after SARS-CoV-2 vaccination and breakthrough infection (BTI) using combined whole-transcriptome and surface proteome single-cell profiling with functional serological and T-cell validation in 58 MM patients. Our results demonstrate that vaccine-responders showed a significant overrepresentation of cytotoxic CD4+ T- and mature CD38+ NK-cells expressing FAS+/TIM3+ with a robust cytokine-responsiveness, such as type-I-interferon-, IL-12- and TNF-α-mediated signaling. Patients with MM experiencing BTI developed strong serological and cellular responses and exhibited similar cytokine-responsive immune cell patterns as vaccine-responders. This study can expand our understanding of molecular and cellular patterns associated with immunization responses and may benefit the design of improved vaccination strategies in immunocompromised patients.


Asunto(s)
COVID-19 , Mieloma Múltiple , Humanos , Vacunas contra la COVID-19 , Citocinas , Leucocitos Mononucleares , Mieloma Múltiple/terapia , SARS-CoV-2 , Vacunación
18.
Infection ; 52(2): 461-469, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37889376

RESUMEN

INTRODUCTION: Falciparum malaria remains one of the deadliest infectious diseases worldwide. In Germany, it is mainly an imported infection among travellers. Rates of coinfection are often unknown, and a clinical rationale for the beneficial use of calculated antibiotic therapy in patients with malaria and suspected coinfection is lacking. METHODS: We conducted an analysis of all in-patients treated with falciparum malaria at a German infectious diseases centre in vicinity to one of Europe's major airports for 2010-2019. Logistic regression and time-to-event analysis were used to evaluate predictors for bacterial coinfection, the use of antibacterial substances, as well as their influence on clinical course. RESULTS: In total, 264 patients were included. Of those, 64% received an additional antibacterial therapy (n = 169). Twenty-nine patients (11.0%) were found to have suffered from a relevant bacterial coinfection, while only a small fraction had relevant bacteremia (n = 3, 1.4%). However, patients with severe malaria did not suffer from coinfections more frequently (p = 0.283). CRP levels were not a reliable predictor for a bacterial coinfection (OR 0.99, 95% CI 0.94-1.06, p = 0.850), while another clinical focus of infection was positively associated (OR 3.86, 95% CI 1.45-11.55, p = 0.010). CONCLUSION: Although bacterial coinfections were rare in patients with malaria at our centre, the risk does not seem negligible. These data point rather towards individual risk assessment in respective patients than to general empiric antibiotic use.


Asunto(s)
Antimaláricos , Coinfección , Enfermedades Transmisibles , Malaria Falciparum , Malaria , Humanos , Coinfección/tratamiento farmacológico , Coinfección/epidemiología , Malaria Falciparum/tratamiento farmacológico , Malaria Falciparum/epidemiología , Antibacterianos/uso terapéutico , Viaje , Enfermedades Transmisibles/tratamiento farmacológico , Antimaláricos/uso terapéutico
19.
AIDS Res Hum Retroviruses ; 40(4): 198-203, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37756364

RESUMEN

Incidence of anal carcinoma (AC) in people living with HIV (PLWH) is increased compared to the general population. Adverse effects of chemoradiotherapy (CRT) on the immune system are associated with a significant detrimental prognosis on overall survival in patients receiving CRT for solid tumors. The aim of this study was to evaluate immunological factors, in particular the differences in recovery of CD4+ and CD8+ cell counts before and after CRT for AC in PLWH. Retrospective single-center chart review extraction to analyze immunological data collected from PLWH with AC; descriptive statistics were used. Thirty-six PLWH with histologically proven AC were included in the analysis. Absolute CD4 cell count 60 months after CRT was 67.2% of the value at the beginning of CRT, whereas the CD8 cell count reached 82.3%. These differences were statistically significant (p = .048), whereas CD4/CD8-ratio remained stable. The findings of the presented study regarding CD4+ and CD8+ cell recovery after CRT are congruent with results from prior studies in non-HIV infected patients. Although not reaching the level of prior CRT T cell numbers, the ability to generate CD8+ cells seems to be better recovered, while CD4+ regeneration is more impaired. These observations are best explained by faster recovery of CD8+ cells via thymic-independent pathways, which are not available for regeneration of CD4+ cells. Further studies with larger numbers of patients are required to analyze the specific CD4+ and CD8+ cell subsets.


Asunto(s)
Neoplasias del Ano , Infecciones por VIH , Humanos , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Estudios Retrospectivos , Linfocitos T CD8-positivos , Linfocitos T CD4-Positivos , Quimioradioterapia , Neoplasias del Ano/terapia , Recuento de Linfocito CD4
20.
PLoS One ; 18(11): e0287725, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37971979

RESUMEN

The SARS-CoV-2 pandemic has affected nations globally leading to illness, death, and economic downturn. Why disease severity, ranging from no symptoms to the requirement for extracorporeal membrane oxygenation, varies between patients is still incompletely understood. Consequently, we aimed at understanding the impact of genetic factors on disease severity in infection with SARS-CoV-2. Here, we provide data on demographics, ABO blood group, human leukocyte antigen (HLA) type, as well as next-generation sequencing data of genes in the natural killer cell receptor family, the renin-angiotensin-aldosterone and kallikrein-kinin systems and others in 159 patients with SARS-CoV-2 infection, stratified into seven categories of disease severity. We provide single-nucleotide polymorphism (SNP) data on the patients and a protein structural analysis as a case study on a SNP in the SIGLEC7 gene, which was significantly associated with the clinical score. Our data represent a resource for correlation analyses involving genetic factors and disease severity and may help predict outcomes in infections with future SARS-CoV-2 variants and aid vaccine adaptation.


Asunto(s)
COVID-19 , Humanos , COVID-19/genética , SARS-CoV-2/genética , Polimorfismo de Nucleótido Simple , Angiotensinas
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