COVID-19 severity and thrombo-inflammatory response linked to ethnicity

Although there is strong evidence that SARS-CoV-2 infection is associated with adverse outcomes in certain ethnic groups, the association of disease severity and risk factors such as comorbidities and biomarkers with racial disparities remains undefined. This retrospective study between March 2020 and February 2021 explores COVID-19 risk factors as predictors for patients’ disease progression through country comparison. Disease severity predictors in Germany and Japan were cardiovascular-associated comorbidities, dementia, and age. We adjusted age, sex, body mass index, and history of cardiovascular disease comorbidity in the country cohorts using a propensity score matching (PSM) technique to reduce the influence of differences in sample size and the surprisingly young, lean Japanese cohort. Analysis of the 170 PSM pairs confirmed that 65.29% of German and 85.29% of Japanese patients were in the uncomplicated phase. More German than Japanese patients were admitted in the complicated and critical phase. Ethnic differences were identified in patients without cardiovascular comorbidities. Japanese patients in the uncomplicated phase presented a suppressed inflammatory response and coagulopathy with hypocoagulation. In contrast, German patients exhibited a hyperactive inflammatory response and coagulopathy with hypercoagulation. These differences were less pronounced in patients in the complicated phase or with cardiovascular diseases. Coagulation/fibrinolysis-associated biomarkers rather than inflammatory-related biomarkers predicted disease severity in patients with cardiovascular comorbidities: platelet counts were associated with severe illness in German patients. In contrast, high D-dimer and fibrinogen levels predicted disease severity in Japanese patients. Our comparative study indicates that ethnicity influences COVID-19-associated biomarker expression linked to the inflammatory and coagulation (thrombo-inflammatory) response. Future studies will be necessary to determine whether these differences contributed to the less severe disease progression observed in Japanese COVID-19 patients compared with those in Germany

Infectiology - Pioneer of Digital Medicine

Was ist neu? Von der personalisierten zur digitalen Medizin uber Impfungen und gezielte Erregerdiagnostik und -therapie ist die Infektionsmedizin Vorreiterin der personalisierten Medizin. Datenprozesse im Rahmen neuer Infektionsepidemien sind Musterbeispiele der Moglichkeiten der digitalen Medizin. Klinische Entscheidungshilfen Die oft gut definierten Krankheitsbilder der Infektiologie und das hohe Niveau der verfugbaren Leitlinien sind ideale Voraussetzungen fur computerunterstutzte Behandlungsentscheidungen. Datengetriebene Infektionsforschung Durch die Verbindung von Daten aus elektronischen Patientenakten mit den umfassenden Datensatzen neuer Technologien aus der sogenannten Omics-Forschung konnen neue Zusammenhange erkannt und Prognosen verbessert werden. Elektronische Gesundheitsakte Die elektronische Gesundheitsakte eroffnet gro ss es Potenzial im Sinne einer zielgerichteten Behandlung, insbesondere bei infektiologischen Notfallen. Telemedizin In Deutschland fehlen Infektiologen, ein Strukturwandel kann nur schrittweise vollzogen werden. Telemedizinische Konsultationen konnen helfen, infektiologische Expertise in unzureichend versorgte Regionen zu bringen. Mobile Health Die fast vollstandige Verbreitung mobiler Digitalgerate schafft neue Moglichkeiten fur die Gestaltung der Arzt-Patient-Kommunikation sowie der heimatnahen Nachsorge. Mobile Versorgung chronischer Infektionen Beim Langzeitmanagement chronischer Erkrankungen sowie bei der Versorgung in Regionen mit schwacher Infrastruktur entstehen Moglichkeiten einer verbesserten medizinischen Behandlung. Balance der Interessen Die Digitale Medizin birgt Risiken durch die Schaffung gro ss er Datensatze mit potenziell stigmatisierenden Patienteninformationen. Softwaresysteme, die Entscheidungen von klinischer Relevanz beeinflussen, bedurfen sorgfaltiger Prufung und Transparenz. Abstract Digital Medicine has become an integral part of clinical infectious diseases. For chronic infections such as HIV and Hepatitis C, treatment with software tools for resistance phenotyping has become standard of care. Computer-assisted decision aids as well as electronic health records are currently being implemented on a regional basis in Germany. They assist physicians in avoiding treatment errors and selecting antibiotics rationally. Mobile devices allow documentation of the course of chronic infections and improve communication between patient and physician. This offers new opportunities in areas with underdeveloped health infrastructure. In the future, it will become possible to integrate complex datasets, such as genome and microbiome, into clinical treatment decisions. This would adjust treatment individually based on host immune response, metabolism, and microbiota colonization

The Role of Microbiota in Preventing Multidrug-Resistant Bacterial Infections

Background: The introduction of industrially produced antibiotics was a milestone in the history of medicine. Now, almost a century later, the adverse consequences of these highly effective drugs have become evident in the form of antibiotic-resistant infections, which are on the rise around the world. The search for solutions to this problem has involved both the introduction of newer types of antibiotics and, increasingly, the development of alternative strategies to prevent infections due to multidrug-resistant bacteria. In this article, we review the pathophysiological connection between the use of antibiotics and the occurrence of such infections. We also discuss some alternative strategies that are currently under development. Methods: This review is based on pertinent articles that appeared from January 2000 to April 2019 and were retrieved by a selective search in the PubMed database employing the search term (microbiota OR microbiome) AND infection. Further suggestions by our author team regarding relevant literature were considered as well. Results: The spectrum of preventive strategies encompasses measures for the protection of the intestinal microbiota (antimicrobial stewardship, neutralization of antibiotic residues in the bowel, use of phages and species-specific antibiotics) as well as measures for its reconstitution (prebiotics, probiotics, and fecal microbiota transfer). Conclusion: In view of the major problem that multidrug-resistant bacteria pose for the world's population and the resources now being spent on the search for a solution, derived both from public funding and from the pharmaceutical industry, we hope to see new, clinically useful approaches being developed and implemented in the near future

Epidemiology of Surgical Site Infections With Staphylococcus aureus in Europe: Protocol for a Retrospective, Multicenter Study

Background: Surgical site infections (SSIs) are among the most common hospital acquired infections. While the incidence of SSI in certain indicator procedures is the subject of ongoing surveillance efforts in hospitals and health care systems around the world, SSI rates vary markedly within surgical categories and are poorly represented by routinely monitored indicator procedures (eg, mastectomy or hernia surgery). Therefore, relying on indicator procedures to estimate the burden of SSI is imprecise and introduces bias as hospitals may take special precautions to achieve lower SSI rates. The most common cause of SSI is Staphylococcus aureus (S. aureus), as recently confirmed by a Europe-wide point-prevalence study conducted by the European Centre for Disease Prevention and Control (ECDC). Objective: The primary objective of this study is to determine the overall and procedure-specific incidence of S. aureus SSI in Europe. Secondary objectives are the overall and procedure-specific outcomes as well as the economic burden of S. aureus SSI in Europe. Explorative objectives are to characterize the composition of the surgical patient population and to estimate the number of patients at risk for S. aureus SSI. Methods: A retrospective, multinational, multicenter cohort study (Staphylococcus aureus Surgical Site Infection Multinational Epidemiology in Europe [SALT] study) with a nested case-control part will be conducted. The study will include all surgical procedures at a participating center in order to prevent selection bias and strengthen the understanding of SSI risk by determining the incidence for all common surgical procedures. Data will be assessed in the cohort population, including 150,000 adult patients who underwent any surgical procedure in 2016, and the case-control population. We will match patients establishing S. aureus SSI 1:1 with controls from the same center. Data on demographics, surgery, and microbiology will be exported from electronic files. More detailed data will be captured from the case-control population. The SALT study will include 13 major or academic surgical centers in Europe, comprising 3 in France, 4 in Germany, 2 in Italy, 3 in Spain, and 1 in the United Kingdom. Sites were selected using a feasibility questionnaire. Results: The SALT study is currently recruiting patients. The aim is to complete recruitment in February 2018 and to close the database in September 2018. The final results are expected by the end of 2018. Conclusions: Results of the SALT study will help to better understand the precise risk of certain procedures. They will also provide insight into the overall and procedure-specific incidence and outcome as well as the economic burden of S. aureus SSI in Europe. Findings of the study may help guide the design of clinical trials for S. aureus vaccines

Management of infections in patients with cancer Responsible use of anti-infectives

Patients with cancer are at increased risk of infection due to disease-associated or therapy-induced immunosuppression. Taking into account globally increasing antimicrobial resistance rates and negative effects associated with antibiotic treatments, the effective, appropriate and guideline-conform use of anti-infectives must be promoted in this clinical setting. The application of antibacterial prophylaxis should be limited to high-risk patients. Infection diagnostics and therapeutic strategies differ depending on the extent of expected immunosuppression and the patient's individual risk factors

Chlorhexidine-containing dressings in the prevention of central venous catheter-related bloodstream infections: A cost and resource utilization analysis

Background: A recent study reported a reduction in probable/definite central venous catheter (CVC)-related bloodstream infections (CRBSIs) in neutropenic high-risk patients using CVC dressings with a chlorhexidine-containing gel pad. Methods: Based on published data, a health-economic analysis was performed to analyze the economic effect of using CVC dressings with a chlorhexidine-containing gel pad compared to non-chlorhexidine control dressings. A micro-costing approach was used to determine CRBSI-related direct treatment cost factors. Results: Between February 2012 and September 2014, 356 patients (178 patients in both groups) were analyzed. Distribution of probable and definite CRBSI in the chlorhexidine group and control group were 12 (7%) vs 18 (10%) and 9 (5%) vs 21 (12%), respectively (P = .011). Median overall length of stay (25 vs 27.5 days: P=.630) and days on treatment with antibacterials (10 vs 12 days: P = .140) were similar between the chlorhexidine and control groups. The most important cost driver in both groups was treatment on general ward ((sic)4275 [US$5173], interquartile range [IQR]: (sic)592 - (sic)6504 [US$ 716 - US$7871] vs (sic)4560 [US$ 5518], IQR: (sic)1227 - (sic)8567 [US$1485 - US$ 10,367]; P=.120), resulting in median overall direct treatment costs of (sic)13,881 (US$16,798) (IQR: (sic)10,922 - (sic)25,457 (US$ 13,217 - US$30,807) vs (sic)13,929 [US$ 16,856] [IQR: (sic)11,295 - (sic)23,561 (US$13,669 - US$ 28,512); P=.640]). Conclusion: Our study shows similar results in overall direct treatment costs, meaning that higher acquisition costs of chlorhexidine-containing dressings did not translate into higher costs. Expenses were primarily outweighed by a lower rate of probable/definite CRBSI and reduced associated costs. (C) 2018 Association for Professionals in Infection Control and Epidemiology. Inc. Published by Elsevier Inc. All rights reserved

HEnRY: a DZIF LIMS tool for the collection and documentation of biomaterials in multicentre studies

Background Well-characterized biomaterials of high quality have great potential for acceleration and quality improvement in translational biomedical research. To improve accessibility of local sample collections, efforts have been made to create central biomaterial banks and catalogues. Available technical solutions for creating professional local sample catalogues and connecting them to central systems are cost intensive and/or technically complex to implement. Therefore, the Translational Thematic Unit HIV of the German Center for Infection Research (DZIF) developed a Laboratory Information and Management System (LIMS) called HIV Engaged Research Technology (HEnRY) for implementation into the Translational Platform HIV (TP-HIV) at the DZIF and other research networks. Results HEnRY is developed at the University Hospital of Cologne. It is an advanced LIMS to manage processing and storage of samples and aliquots of different sample types. Features include: monitoring of stored samples and associated information data selection via query tools or Structured Query Language (SQL) preparation of summary documents, including scannable search lists centralized management of the practical laboratory part of multicentre studies (e.g. import of drawing schemes and sample processing steps), preparation of aliquot shipments, including associated documents to be added to shipments unique and secure identification of aliquots through use of customizable Quick Response (QR) code labels directly from HEnRY support of aliquot data transmission to central registries. In summary, HEnRY offers all features necessary for a LIMS software. In addition, the structure of HEnRY provides sufficient flexibility to allow the implementation in other research areas. Conclusion HEnRY is a free biobanking tool published under the MIT license. While it was developed to support HIV research in Germany, the feature set and language options, allow much broader applications and make this a powerful free research tool

Clinical Impact of Rapid Species Identification From Positive Blood Cultures With Same-day Phenotypic Antimicrobial Susceptibility Testing on the Management and Outcome of Bloodstream Infections

Background. Timely availability of microbiological results from positive blood cultures is essential to enable early pathogen-directed therapy. The Accelerate Pheno system (ADX) is a novel technology using fluorescence in situ hybridization for rapid species identification (ID) and morphokinetic bacterial analysis for phenotypic antimicrobial susceptibility testing (AST), with promising results. Yet the impact of this technology on clinical management and patient outcome remains unclear. Methods. We conducted a quasiexperimental before-and-after observational study and analyzed 3 groups with different diagnostic and therapeutic pathways following recent integration of ADX: conventional microbiological diagnostics with and without antimicrobial stewardship program (ASP) intervention, and rapid diagnostics (ADX in addition to conventional standard) with ASP intervention. Primary endpoints were time to adequate, to optimal and to step-down antimicrobial therapy. Secondary endpoints were antimicrobial consumption, in-hospital mortality, length of stay (LOS), and the incidence of Clostridioides difficile infection (CDI). Results. Two hundred four patients (conventional diagnostics, n = 64; conventional diagnostics + ASP, n = 68; rapid diagnostics + ASP; n = 72) were evaluated. The use of ADX significantly decreased time from Gram stain to ID (median, 23 vs 2.2 hours, P <.001) and AST (median, 23 vs 7.4 hours, P <.001), from Gram stain to optimal therapy (median, 11 vs 7 hours, P =.024) and to step-down antimicrobial therapy (median, 27.8 vs 12 hours, P =.019). However, groups did not differ in antimicrobial consumption, duration of antimicrobial therapy, mortality, LOS, or incidence of CDI. Conclusions. Use of ADX significantly reduced time to ID and AST as well as time to optimal antimicrobial therapy but did not affect antimicrobial consumption and clinical outcome

The Role of Previous Therapies and Sites of Metastasis as Influencing Factors on Discordance of ER, PR and HER2 Status Between Primary and Metastasized Breast Cancer

Background/Aim: The aim of the present study was to analyze metastasized breast cancer (BC) patients with regard to the discordance of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2). We especially aimed to analyze the association between the change of tumor biology and previous treatment or metastatic sites. Patients and Methods: Patients with metastasized BC who were treated at the Department of Gynecology/Breast Center of the University Hospital of Cologne were analyzed. Results: Loss of HER2 occurred more frequently in lymph node metastases that were not in the axillary region (p=0.026). Letrozole showed a significant correlation with loss of ER and/or PR (p=0.041). Improved overall survival and post-metastasis survival were noticed with a gain of HER2 (p=0.044 and p=0.009, respectively) and concordant positive ER and PR status (p=0.002 and p=0.001, respectively). Conclusion: The discordance of receptors and the dependence of BC on therapies as well as metastatic sites stresses the necessity of early sample taking to offer patients suitable therapy options

Clinical and pharmacoeconomic evaluation of antifungal prophylaxis with continuous micafungin in patients undergoing allogeneic stem cell transplantation: A six-year cohort analysis

Background Patients undergoing allogeneic stem cell transplantation (aSCT) are at high risk to develop an invasive fungal disease (IFD). Optimisation of antifungal prophylaxis strategies may improve patient outcomes and reduce treatment costs. Objectives To analyse the clinical and economical impact of using continuous micafungin as antifungal prophylaxis. Patients/Methods We performed a single-centre evaluation comparing patients who received either oral posaconazole with micafungin as intravenous bridging as required (POS-MIC) to patients who received only micafungin (MIC) as antifungal prophylaxis after aSCT. Epidemiological, clinical and direct treatment cost data extracted from the Cologne Cohort of Neutropenic Patients (CoCoNut) were analysed. Results Three hundred and thirteen patients (97 and 216 patients in the POS-MIC and MIC groups, respectively) were included into the analysis. In the POS-MIC and MIC groups, median overall length of stay was 42 days (IQR: 35-52 days) vs 40 days (IQR: 35-49 days; p = .296), resulting in median overall costs of euro42,964 (IQR: euro35,040-euro56,348) vs euro43,291 (IQR: euro37,281 vs euro51,848; p = .993), respectively. Probable/proven IFD in the POS-MIC and MIC groups occurred in 5 patients (5%) vs 3 patients (1%; p = .051), respectively. The Kaplan-Meier analysis showed improved outcome of patients in the MIC group at day 100 (p = .037) and day 365 (p < .001) following aSCT. Conclusions Our study results demonstrate improved outcomes in the MIC group compared with the POS-MIC group, which can in part be explained by a tendency towards less probable/proven IFD. Higher drug acquisition costs of micafungin did not translate into higher overall costs