TY - JOUR A1 - Boch, Tobias A1 - Spiess, Birgit A1 - Heinz, Werner A1 - Cornely, Oliver A. A1 - Schwerdtfeger, Rainer A1 - Hahn, Joachim A1 - Krause, Stefan W. A1 - Duerken, Matthias A1 - Bertz, Hartmut A1 - Reuter, Stefan A1 - Kiehl, Michael A1 - Claus, Bernd A1 - Deckert, Peter Markus A1 - Hofmann, Wolf‐Karsten A1 - Buchheidt, Dieter A1 - Reinwald, Mark T1 - Aspergillus specific nested PCR from the site of infection is superior to testing concurrent blood samples in immunocompromised patients with suspected invasive aspergillosis JF - Mycoses N2 - Invasive aspergillosis (IA) is a severe complication in immunocompromised patients. Early diagnosis is crucial to decrease its high mortality, yet the diagnostic gold standard (histopathology and culture) is time‐consuming and cannot offer early confirmation of IA. Detection of IA by polymerase chain reaction (PCR) shows promising potential. Various studies have analysed its diagnostic performance in different clinical settings, especially addressing optimal specimen selection. However, direct comparison of different types of specimens in individual patients though essential, is rarely reported. We systematically assessed the diagnostic performance of an Aspergillus‐specific nested PCR by investigating specimens from the site of infection and comparing it with concurrent blood samples in individual patients (pts) with IA. In a retrospective multicenter analysis PCR was performed on clinical specimens (n = 138) of immunocompromised high‐risk pts (n = 133) from the site of infection together with concurrent blood samples. 38 pts were classified as proven/probable, 67 as possible and 28 as no IA according to 2008 European Organization for Research and Treatment of Cancer/Mycoses Study Group consensus definitions. A considerably superior performance of PCR from the site of infection was observed particularly in pts during antifungal prophylaxis (AFP)/antifungal therapy (AFT). Besides a specificity of 85%, sensitivity varied markedly in BAL (64%), CSF (100%), tissue samples (67%) as opposed to concurrent blood samples (8%). Our results further emphasise the need for investigating clinical samples from the site of infection in case of suspected IA to further establish or rule out the diagnosis. KW - antifungal KW - aspergillosis KW - BAL KW - blood KW - cerebrospinal fluid KW - comparison KW - PCR KW - Aspergillus Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-214065 VL - 62 IS - 11 SP - 1035 EP - 1042 ER - TY - JOUR A1 - Marischen, Lothar A1 - Englert, Anne A1 - Schmitt, Anna-Lena A1 - Einsele, Hermann A1 - Loeffler, Juergen T1 - Human NK cells adapt their immune response towards increasing multiplicities of infection of Aspergillus fumigatus JF - BMC Immunology N2 - Background: The saprophytic fungus Aspergillus fumigatus reproduces by generation of conidia, which are spread by airflow throughout nature. Since humans are inhaling certain amounts of spores every day, the (innate) immune system is constantly challenged. Even though macrophages and neutrophils carry the main burden, also NK cells are regarded to contribute to the antifungal immune response. While NK cells reveal a low frequency, expression and release of immunomodulatory molecules seem to be a natural way of their involvement. Results: In this study we show, that NK cells secrete chemokines such as CCL3/MIP-1α, CCL4/MIP-1β and CCL5/RANTES early on after stimulation with Aspergillus fumigatus and, in addition, adjust the concentration of chemokines released to the multiplicity of infection of Aspergillus fumigatus. Conclusions: These results further corroborate the relevance of NK cells within the antifungal immune response, which is regarded to be more and more important in the development and outcome of invasive aspergillosis in immunocompromised patients after hematopoietic stem cell transplantation. Additionally, the correlation between the multiplicity of infection and the expression and release of chemokines shown here may be useful in further studies for the quantification and/or surveillance of the NK cell involvement in antifungal immune responses. KW - Aspergillus fumigatus KW - aspergillosis KW - NK cells KW - chemokines KW - CCL4 KW - multiplicity of infection KW - MIP-1β Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-176331 VL - 19 IS - 39 ER - TY - JOUR A1 - Mousset, Sabine A1 - Buchheidt, Dieter A1 - Heinz, Werner A1 - Ruhnke, Markus A1 - Cornely, Oliver A. A1 - Egerer, Gerlinde A1 - Krüger, William A1 - Link, Hartmut A1 - Neumann, Silke A1 - Ostermann, Helmut A1 - Panse, Jens A1 - Penack, Olaf A1 - Rieger, Christina A1 - Schmidt-Hieber, Martin A1 - Silling, Gerda A1 - Südhoff, Thomas A1 - Ullmann, Andrew J. A1 - Wolf, Hans-Heinrich A1 - Maschmeyer, Georg A1 - Böhme, Angelika T1 - Treatment of invasive fungal infections in cancer patients—updated recommendations of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Oncology (DGHO) JF - Annals of Hematology N2 - Invasive fungal infections are a main cause of morbidity and mortality in cancer patients undergoing intensive chemotherapy regimens. Early antifungal treatment is mandatory to improve survival. Today, a number of effective and better-tolerated but more expensive antifungal agents compared to the former gold standard amphotericin B deoxycholate are available. Clinical decision-making must consider results from numerous studies and published guidelines, as well as licensing status and cost pressure. New developments in antifungal prophylaxis improving survival rates result in a continuous need for actualization. The treatment options for invasive Candida infections include fluconazole, voriconazole, and amphotericin B and its lipid formulations, as well as echinocandins. Voriconazole, amphotericin B, amphotericin B lipid formulations, caspofungin, itraconazole, and posaconazole are available for the treatment of invasive aspergillosis. Additional procedures, such as surgical interventions, immunoregulatory therapy, and granulocyte transfusions, have to be considered. The Infectious Diseases Working Party of the German Society of Hematology and Oncology here presents its 2008 recommendations discussing the dos and do-nots, as well as the problems and possible solutions, of evidence criteria selection. KW - cancer KW - invasive fungal infections KW - antifungals KW - mycoses KW - hematologic malignancies KW - aspergillosis KW - antifungal agents KW - invasive candidiasis Y1 - 2014 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-121340 VL - 96 ER - TY - JOUR A1 - Amich, Jorge A1 - Krappmann, Sven T1 - Deciphering metabolic traits of the fungal pathogen Aspergillus fumigatus: redundancy vs. essentiality JF - Frontiers in Microbiology N2 - Incidence rates of infections caused by environmental opportunistic fungi have risen over recent decades. Aspergillus species have emerged as serious threat for the immunecompromised, and detailed knowledge about virulence-determining traits is crucial for drug target identification. As a prime saprobe, A. fumigatus has evolved to efficiently adapt to various stresses and to sustain nutritional supply by osmotrophy, which is characterized by extracellular substrate digestion followed by efficient uptake of breakdown products that are then fed into the fungal primary metabolism. These intrinsic metabolic features are believed to be related with its virulence ability. The plethora of genes that encode underlying effectors has hampered their in-depth analysis with respect to pathogenesis. Recent developments in Aspergillus molecular biology allow conditional gene expression or comprehensive targeting of gene families to cope with redundancy. Furthermore, identification of essential genes that are intrinsically connected to virulence opens accurate perspectives for novel targets in antifungal therapy. KW - Aspergillus fumigatus KW - aspergillosis KW - virulence KW - conditional promoter replacement KW - nutrients KW - gene family targeting Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-123669 VL - 3 ER -