Institut für Hygiene und Mikrobiologie
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Sonstige beteiligte Institutionen
- Department of Hematology and Oncology, Sana Hospital Hof, Hof, Germany (1)
- Department of Laboratory Medicine and Medicine Huddinge, Karolinska Institutet and University Hospital, Stockholm, Sweden (1)
- Department of Medicine A, University Hospital of Münster, Münster, Germany (1)
- Instituto de Higiene, Universidad de la República, Montevideo, Uruguay (1)
- Instituto de Hygiene Montevideo, Uruguay (1)
- Krankenhaushygiene und Antimicrobial Stewardship (1)
- Krankenhaushygiene und Antimicrobial Stewardship (Universitätsklinikum) (1)
- Leibniz-Institut für Naturstoff-Forschung und Infektionsbiologie Hans-Knöll-Institut (1)
- Nationales Referenzzentrum für Invasive Pilzinfektionen (NRZMyk) (1)
- Nationales Referenzzentrum für invasive Pilzinfektionen (1)
EU-Project number / Contract (GA) number
- 2016 FGR 0053 (1)
- 278864 (1)
Echinococcosis is an important zoonosis. The causative agent of Alveolar Echinococcosis (AE) is Echinococcus multilocularis. The treatment of human AE is limited to surgery and chemotherapy with albendazole (ABZ). However, ABZ works only parasitostatically and it needs to be taken for long periods, although it causes adverse side effects. Thus, development of new, parasiticidal drug with selective toxicity is required. Because undifferentiated stem cells of E. multilocularis play key role in its longevity and regenerative capacity, targeting stem cells is especially important.
In vitro screening of protein kinases inhibitors demonstrated that human PIM kinases inhibitors have detrimental effects on E. multilocularis. Through yeast two hybrid assay, the interaction of parasite PIM kinase (EmPIM) and its CDC25 (EmCDC25) was indicated. Through in situ hybridization, expression of EmPIM in the stem cells was observed. Therefore, EmPim is likely to be a positive regulator of cell cycle progression, the same as human Pim1. In addition, 20 compounds against EmPIM were selected through in silico screening and synthesized. One of them has a detrimental effect on E.multilocularis comparable to human pan-PIM inhibitors, but has much weaker toxicity on human cell lines.
Furthermore, triclabendazole (TCBZ) and its metabolite TCBZSX, which are approved for another flatworm disease, Fascioliasis were tried on E. multilocularis. With two stem cell markers, damage to stem cells by TCBZSX was shown. In addition, primary cells from treated vesicles never regenerated and the damage to stem cells proved to be irreversible.
Our in silico screening method used in EmPIM research has potential to identify compounds which overcome the side effect problem in ABZ-based chemotherapy. On the other hand, it is expected that my research of TCBZ can lead to development of a practical parasiticidal chemotherapy by combining TCBZ, which damages stem cells, and ABZ, which damages differentiated cells.
High seroprevalence of SARS-CoV-2 in Mwanza, northwestern Tanzania: a population-based survey
(2022)
The transmission of the SARS-CoV-2 virus, which causes COVID-19, has been documented worldwide. However, the evidence of the extent to which transmission has occurred in different countries is still to be established. Understanding the magnitude and distribution of SARS-CoV-2 through seroprevalence studies is important in designing control and preventive strategies in communities. This study investigated the seropositivity of the SARS-CoV-2 virus antibodies in the communities of three different districts in the Mwanza region, Tanzania. A household cross-sectional survey was conducted in September 2021 using the modified African Centre for Disease and Prevention (ACDC) survey protocol. A blood sample was obtained from one member of each of the selected households who consented to take part in the survey. Immunochromatographic rapid test kits were used to detect IgM and IgG SARS-CoV-2 antibodies, followed by descriptive data analysis. Overall, 805 participants were enrolled in the study with a median age of 35 (interquartile range (IQR):27–47) years. The overall SARS-CoV-2 seropositivity was 50.4% (95%CI: 46.9–53.8%). The IgG and IgM seropositivity of the SARS-CoV-2 antibodies was 49.3% and 7.2%, respectively, with 6.1% being both IgG and IgM seropositive. A history of runny nose (aOR: 1.84, 95%CI: 1.03–3.5, p = 0.036), loss of taste (aOR: 1.84, 95%CI: 1.12–4.48, p = 0.023), and living in Ukerewe (aOR: 3.55, 95%CI: 1.68–7.47, p = 0.001) and Magu (aOR: 2.89, 95%CI: 1.34–6.25, p= 0.007) were all independently associated with SARS-CoV-2 IgM seropositivity. Out of the studied factors, living in the Ukerewe district was independently associated with IgG seropositivity (aOR 1.29, CI 1.08–1.54, p = 0.004). Twenty months after the first case of COVID-19 in Tanzania, about half of the studied population in Mwanza was seropositive for SARS-CoV-2.
Candida auris was first described as a yeast pathogen in 2009. Since then, the species has emerged worldwide. In contrast to most other Candida spp., C. auris frequently exhibits multi-drug resistance and is readily transmitted in hospital settings. While most detections so far are from colonised patients, C. auris does cause superficial and life-threatening invasive infections. During management of the first documented C. auris transmission in a German hospital, experts from the National Reference Centers for Invasive Fungal Infections (NRZMyk) and the National Reference Center for Surveillance of Nosocomial Infections screened available literature and integrated available knowledge on infection prevention and C. auris epidemiology and biology to enable optimal containment. Relevant recommendations developed during this process are summarised in this guidance document, intended to assist in management of C. auris transmission and potential outbreak situations. Rapid and effective measures to contain C. auris spread require a multi-disciplinary approach that includes clinical specialists of the affected unit, nursing staff, hospital hygiene, diagnostic microbiology, cleaning staff, hospital management and experts in diagnostic mycology / fungal infections. Action should be initiated in a step-wise process and relevant interventions differ between management of singular C. auris colonised / infected patients and detection of potential C. auris transmission or nosocomial outbreaks.
Diagnosis and therapy of Mycobacterium marinum: a single-center 21-year retrospective analysis
(2022)
Background and Objectives
In Europe, infections with Mycobacterium (M.) marinum are rare. We conducted a retrospective single-center study to assess the clinical spectrum of M. marinum infection and its diagnosis, treatment and outcome under real-world conditions.
Patients and Methods
Eighteen patients presenting with M. marinum infections between 1998 and 2018 were identified in the data warehouse of the University Hospital Würzburg and considered for detailed analysis.
Results
Twelve patients reported aquatic exposure. In 16/18 cases the upper extremities were affected. No invasive infections were detected. Mean time to diagnosis was 15 weeks. Histology revealed granulomatous inflammation in 14 patients while mycobacterial cultures were positive for M. marinum in 16 cases. Most patients received antibiotic monotherapy (14/18) while combination therapy was administered in four cases. Treatment (with a median duration of 10 weeks) was successful in 13 patients. Five patients were lost to follow-up.
Conclusions
Our retrospective analysis of M. marinum infections at a German tertiary referral center revealed a considerable diagnostic delay and the relevance of microbiological culture, PCR and histology for diagnosis. Monotherapy with clarithromycin (rather than doxycycline) appeared as a reasonable treatment option while immunosuppressed or -compromised patients and those with extended disease received combination therapy.
Purpose
Fungal biomarkers support early diagnosis of invasive fungal infections. In this study, we evaluated the impact of a recent update to the manufacturer‐recommended cut‐off for beta‐1,3‐D‐glucan (BDG) testing (Fujifilm Wako BDG assay) on sensitivity and specificity for the detection of candidemia. Additionally, we compared the performance with tests for Candida antigen (Ag by Serion ELISA antigen Candida, Virion\Serion) and anti‐mannan antibodies (Ab by Hemkit Candida IHA, Ravo Diagnostika).
Methods
Sera of 82 patients with candidemia, which were sampled with a maximum distance of ±14 days from the date of sampling of the corresponding positive blood cultures, were retrospectively analysed for BDG, Ag and Ab. Results of BDG testing were compared with results from sera of 129 patients with candidemia from a different hospital.
Results
Sensitivity of BDG testing (47%) was higher than for Ag (17%) or Ab (20%). By combining Ag and Ab testing, sensitivity was raised to 32%. Lowering the cut‐off of BDG from 11 pg/ml to the newly recommended cut‐off of 7 pg/ml resulted in a significant increase in sensitivity (47% vs 58%, p = .01 and 63% vs 71% p < .01). At both centres, the increase was significant in NAC but not in C. albicans candidemia. No significant effects on specificity were observed.
Conclusion
BDG testing outperformed Ag and Ab testing and its combination. Lowering the BDG cut‐off had no significant impact on specificity. The increase in sensitivity can be mainly attributed to a gain in sensitivity for non‐albicans Candida species bloodstream infections.
Bei dem 2009 erstbeschriebenen Hefepilz C. auris handelt es sich um einen Keim, welcher aufgrund von nosokomialen Ausbrüchen und hohen Antimykotikaresistenzen Aufmerksamkeit erregte. Ziel dieser Arbeit war es in Deutschland gesammelte Isolate bezüglich vorhandener Resistenzen und Mutationen in Resistenzregionen zu testen und das epidemiologische Geschehen hierzulande mit dem globalen Auftreten des Keims zu vergleichen. Bezüglich der durchgeführten Resistenztestungen wiesen die CLSI-konformen Testarten (YO-Platten und E-Test-Verfahren) meist vergleichbare Ergebnisse auf. Für das EUCAST-konforme Mikrodilutionstestverfahren kann aufgrund eines stark ausgeprägten paradoxen Wachstumseffekts nur Anidulafungin, nicht jedoch Caspofungin, zur Testung empfohlen werden. Insgesamt erwiesen sich 25 % der Isolate als Caspofungin-resistent. Zwei Isolate zeigten eine Resistenz gegenüber allen getesteten Echinocandinen (16,7 %). Die höchsten Resistenzraten wurden gegenüber Fluconazol (92 %) beobachtet. Zwei der Isolate zeigten sich gegenüber Voriconazol resistent (16,7 %). Für Amphotericin B konnte eine Resistenzrate von 33,3 % festgestellt werden. Für die Wirkstoffe Posaconazol und Itraconazol erwiesen sich alle untersuchten Isolate als sensitiv. Dies konnte auch mit Ausnahme eines Isolates für 5-Flucytosin beobachtet werden. Die durch eine Sanger-Sequenzierung erhaltenen Sequenzen der Gene FKS1 und ERG11 wurden auf Mutationen untersucht, welche zu Aminosäuresubstitutionen im Gesamtprotein führten. Hierbei ergaben sich für zwei Isolate (16,7 %) Mutationen im FKS1-Hot Spot 1 (Typ S639F und S639Y). Beide Isolate zeigten sich in den AFST Echinocandin-resistent. Bei allen untersuchten Isolaten lagen Mutationen im ERG11 Gen vor. So fand sich in 8 Fällen eine Mutation des Typen Y132F (66,7 %), in 3 Fällen der Typ K143R (25 %) und in einem Fall der Typ F126L (8,3 %). Im Rahmen eines anderen Projekts wurde mit den hier gewonnenen PCR-Produkten ein WGS durchgeführt, um die Isolate durch SNPs-Vergleich mit Referenzstämmen phylogenetischen Clades zuzuordnen. Dabei konnten 91,7 % der Isolate dem südasiatischen Clade I und ein Isolat dem südafrikanischen Clade III zugeordnet werden. Aufgrund der geringen epidemiologischen Fallzahlen in Deutschland scheint gegenwärtig keine Bedrohung von C. auris auszugehen. Berichte aus anderen Ländern konnten allerdings eine rasche, ausbruchartige Zunahme von C. auris Fällen nachweisen. So kann nur angeraten werden das infektiologische Geschehen in Deutschland weiterhin zu beobachten.
The Indigenous tribe called the Wiwa lives retracted in the Sierra Nevada de Santa Marta, Colombia. Little is known about their health status and whether the health care system in place covers their needs. In 2017 and 2018, a permanent physician was in charge for the Wiwa. Diseases and complaints were registered, ranked, and classified with the ICD-10 coding. Datasets from the Indigenous health care provider Dusakawi, collected from local health points and health brigades travelling sporadically into the fields for short visits, were compared. Furthermore, a list of provided medication was evaluated regarding the recorded needs. The most common complaints found were respiratory, infectious and parasitic, and digestive diseases. The top ten diagnoses collected in the health points and in the health brigade datasets were similar, although with a different ranking. The available medication showed a basic coverage only, with a critical lack of treatment for many severe, chronic, and life-threatening diseases. Most of the detected diseases in the Indigenous population are avoidable by an improvement in health care access, an expansion of the provided medication, and an increase in knowledge, hygiene, and life standards.
Outpatient antibiotic use is closely related to antimicrobial resistance and in Germany, almost 70% of antibiotic prescriptions in human health are issued by primary care physicians (PCPs). The aim of this study was to explore PCPs, namely General Practitioners' (GPs) and outpatient pediatricians' (PDs) knowledge of guideline recommendations on rational antimicrobial treatment, the determinants of confidence in treatment decisions and the perceived need for training in this topic in a large sample of PCPs from southern Germany. Out of 3753 reachable PCPs, 1311 completed the survey (overall response rate = 34.9%). Knowledge of guideline recommendations and perceived confidence in making treatment decisions were high in both GPs and PDs. The two highest rated influencing factors on prescribing decisions were reported to be guideline recommendations and own clinical experiences, hence patients' demands and expectations were judged as not influencing treatment decisions. The majority of physicians declared to have attended at least one specific training course on antibiotic use, yet almost all the participating PCPs declared to need more training on this topic. More studies are needed to explore how consultation-related and context-specific factors could influence antibiotic prescriptions in general and pediatric primary care in Germany beyond knowledge. Moreover, efforts should be undertaken to explore the training needs of PCPs in Germany, as this would serve the development of evidence-based educational interventions targeted to the improvement of antibiotic prescribing decisions rather than being focused solely on knowledge of guidelines.
Fungal eye infections can lead to loss of vision and blindness. The disease is most prevalent in the tropics, although case numbers in moderate climates are increasing as well. This study aimed to determine the dominating filamentous fungi causing eye infections in Germany and their antifungal susceptibility profiles in order to improve treatment, including cases with unidentified pathogenic fungi. As such, we studied all filamentous fungi isolated from the eye or associated materials that were sent to the NRZMyk between 2014 and 2020. All strains were molecularly identified and antifungal susceptibility testing according to the EUCAST protocol was performed for common species. In total, 242 strains of 66 species were received. Fusarium was the dominating genus, followed by Aspergillus, Purpureocillium, Alternaria, and Scedosporium. The most prevalent species in eye samples were Fusarium petroliphilum, F. keratoplasticum, and F. solani of the Fusarium solani species complex. The spectrum of species comprises less susceptible taxa for amphotericin B, natamycin, and azoles, including voriconazole. Natamycin is effective for most species but not for Aspergillus flavus or Purpureocillium spp. Some strains of F. solani show MICs higher than 16 mg/L. Our data underline the importance of species identification for correct treatment.