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  • 1
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    A first update on mapping the human genetic architecture of COVID-19
    Springer Science and Business Media LLC ; 2022
    In:  Nature Vol. 608, No. 7921 ( 2022-08-04), p. E1-E10
    Details
    In: Nature, Springer Science and Business Media LLC, Vol. 608, No. 7921 ( 2022-08-04), p. E1-E10
    Materialart: Online-Ressource
    ISSN: 0028-0836 , 1476-4687
    URL: Article
    DOI: 10.1038/s41586-022-04826-7
    RVK:
    TA 1000
    RVK:
    UA 1000
    RVK:
    WA 15000
    Sprache: Englisch
    Verlag: Springer Science and Business Media LLC
    Publikationsdatum: 2022
    ZDB Id: 120714-3
    ZDB Id: 1413423-8
    SSG: 11
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 2
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    Trends of the Epidemiology of Candidemia in Switzerland: A 15-Year FUNGINOS Survey
    Oxford University Press (OUP) ; 2021
    In:  Open Forum Infectious Diseases Vol. 8, No. 10 ( 2021-10-01)
    Details
    In: Open Forum Infectious Diseases, Oxford University Press (OUP), Vol. 8, No. 10 ( 2021-10-01)
    Kurzfassung: The increasing incidence of candidemia and emergence of drug-resistant Candida species are major concerns worldwide. Long-term surveillance studies are needed. Methods The Fungal Infection Network of Switzerland (FUNGINOS) conducted a 15-year (2004–2018), nationwide, epidemiological study of candidemia. Hospital-based incidence of candidemia, Candida species distribution, antifungal susceptibility, and consumption were stratified in 3 periods (2004–2008, 2009–2013, 2014–2018). Population-based incidence over the period 2009–2018 derived from the Swiss Antibiotic Resistance Surveillance System (ANRESIS). Results A total of 2273 Candida blood isolates were studied. Population and hospital-based annual incidence of candidemia increased from 2.96 to 4.20/100 000 inhabitants (P = .022) and 0.86 to 0.99/10 000 patient-days (P = .124), respectively. The proportion of Candida albicans decreased significantly from 60% to 53% (P = .0023), whereas Candida glabrata increased from 18% to 27% (P & lt; .0001). Other non-albicans Candida species remained stable. Candida glabrata bloodstream infections occurred predominantly in the age group 18–40 and above 65 years. A higher proportional increase of C glabrata was recorded in wards (18% to 29%, P & lt; .0001) versus intensive care units (19% to 24%, P = .22). According to Clinical and Laboratory Standards Institute, nonsusceptibility to fluconazole in C albicans was observed in 1% of isolates, and anidulafungin and micafungin nonsusceptibility was observed in 2% of C albicans and C glabrata. Fluconazole consumption, the most frequently used antifungal, remained stable, whereas use of mold-active triazoles and echinocandins increased significantly in the last decade (P & lt; .0001). Conclusions Over the 15-year period, the incidence of candidemia increased. A species shift toward C glabrata was recently observed, concurring with increased consumption of mold-active triazoles.
    Materialart: Online-Ressource
    ISSN: 2328-8957
    URL: Article
    DOI: 10.1093/ofid/ofab471
    Sprache: Englisch
    Verlag: Oxford University Press (OUP)
    Publikationsdatum: 2021
    ZDB Id: 2757767-3
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 3
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    Mapping the human genetic architecture of COVID-19
    Springer Science and Business Media LLC ; 2021
    In:  Nature Vol. 600, No. 7889 ( 2021-12-16), p. 472-477
    Details
    In: Nature, Springer Science and Business Media LLC, Vol. 600, No. 7889 ( 2021-12-16), p. 472-477
    Kurzfassung: The genetic make-up of an individual contributes to the susceptibility and response to viral infection. Although environmental, clinical and social factors have a role in the chance of exposure to SARS-CoV-2 and the severity of COVID-19 1,2 , host genetics may also be important. Identifying host-specific genetic factors may reveal biological mechanisms of therapeutic relevance and clarify causal relationships of modifiable environmental risk factors for SARS-CoV-2 infection and outcomes. We formed a global network of researchers to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity. Here we describe the results of three genome-wide association meta-analyses that consist of up to 49,562 patients with COVID-19 from 46 studies across 19 countries. We report 13 genome-wide significant loci that are associated with SARS-CoV-2 infection or severe manifestations of COVID-19. Several of these loci correspond to previously documented associations to lung or autoimmune and inflammatory diseases 3–7 . They also represent potentially actionable mechanisms in response to infection. Mendelian randomization analyses support a causal role for smoking and body-mass index for severe COVID-19 although not for type II diabetes. The identification of novel host genetic factors associated with COVID-19 was made possible by the community of human genetics researchers coming together to prioritize the sharing of data, results, resources and analytical frameworks. This working model of international collaboration underscores what is possible for future genetic discoveries in emerging pandemics, or indeed for any complex human disease.
    Materialart: Online-Ressource
    ISSN: 0028-0836 , 1476-4687
    URL: Article
    DOI: 10.1038/s41586-021-03767-x
    RVK:
    TA 1000
    RVK:
    UA 1000
    RVK:
    WA 15000
    Sprache: Englisch
    Verlag: Springer Science and Business Media LLC
    Publikationsdatum: 2021
    ZDB Id: 120714-3
    ZDB Id: 1413423-8
    SSG: 11
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 4
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    Clinical Considerations of Isavuconazole Administration in High-Risk Hematological Patients: A Single-Center 5-Year Experience
    Springer Science and Business Media LLC ; 2021
    In:  Mycopathologia Vol. 186, No. 6 ( 2021-12), p. 775-788
    Details
    In: Mycopathologia, Springer Science and Business Media LLC, Vol. 186, No. 6 ( 2021-12), p. 775-788
    Kurzfassung: There are limited real-life data on isavuconazole prophylaxis and treatment of invasive mold infections (IMI) in hematological patients and allogeneic hematopoietic cell transplant (HCT) recipients. Objectives Primary objective was to describe the indications of real-life isavuconazole administration at a university hospital. Secondary objectives included the description of liver function tests and QTc interval between baseline and end of treatment (EOT), clinical outcomes and breakthrough IMI by the EOT. Patients/Methods This was a 5-year single-center retrospective study of all adult patients with acute myeloid leukemia and/or allogeneic HCT recipients who received isavuconazole as prophylaxis and/or treatment between June 1, 2016, and July 31, 2020. Results Among 30 identified patients, the indications for isavuconazole administration were adverse events associated with prior antifungal treatment ( N : 18, 60%: hepatotoxicity, renal insufficiency, long QTc interval, neurotoxicity, and potential drug–drug interactions in 6, 4, 3, 1 and 4 patients, respectively), clinical efficacy ( N : 5, 16.6%), and other reasons ( N : 10, 33.3%; 5/10 patients treated with isavuconazole to facilitate hospital discharge with orally administered appropriate treatment). Alanine aminotransferase significantly decreased from baseline (mean: 129 IU/L, range: 73, 202) to a mean of 48 IU/L (range: 20, 80) by day 14 ( P -value: 0.02), 23.5 IU/L (range: 20, 27) by day 28 ( P -value: 0.03) and 16.5 IU/L (range: 16, 17) by day 42 ( P -value: 0.009). The QTc interval decreased from baseline (mean: 456.8 ms, range: 390, 533) to EOT (mean: 433.8 ms, range: 400, 472; P -value: 0.03). The mean isavuconazole plasma concentration was 2.9 mg/L (range: 0.9, 6.7). There was no breakthrough IMI observed. Conclusion Isavuconazole is a safe and reliable antifungal agent in complex hematological patients, with relatively low hepatotoxicity and QTc interval shortening properties.
    Materialart: Online-Ressource
    ISSN: 0301-486X , 1573-0832
    URL: Article
    DOI: 10.1007/s11046-021-00583-9
    Sprache: Englisch
    Verlag: Springer Science and Business Media LLC
    Publikationsdatum: 2021
    ZDB Id: 2003647-4
    SSG: 12
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 5
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    Safety and efficacy of intravenously administered cidofovir in adult haematopoietic cell transplant recipients: a retrospective multicentre cohort study
    Oxford University Press (OUP) ; 2021
    In:  Journal of Antimicrobial Chemotherapy Vol. 76, No. 11 ( 2021-10-11), p. 3020-3028
    Details
    In: Journal of Antimicrobial Chemotherapy, Oxford University Press (OUP), Vol. 76, No. 11 ( 2021-10-11), p. 3020-3028
    Kurzfassung: To evaluate the safety and efficacy of cidofovir for the treatment of double-stranded DNA (dsDNA) viral infections following allogeneic haematopoietic cell transplant (HCT). Methods This was a retrospective multicentre cohort study including adult HCT recipients who received ≥1 dose of IV-administered cidofovir for any dsDNA viral infection from 2006 to 2019. The objectives were to describe the rate of and risk factors for nephrotoxicity and virological response by the end of treatment (EOT). Results We included 165 patients from nine centres. Cidofovir was administered at 5 mg/kg/week (N = 115; 69.7%), 1 mg/kg/week (18; 10.9%), 3 mg/kg/week (12; 7.3%) or 1 mg/kg three times/week (11; 6.7%). Cidofovir was administered for adenovirus, cytomegalovirus (CMV) and BK virus infection in 75 (45.5%), 64 (38.8%) and 51 (30.9%) patients, respectively. Among 158 patients with renal function data at baseline and EOT, 40 (25.3%) developed nephrotoxicity. In multivariable analyses, age (OR 1.04; P = 0.05), weight (OR 1.05; P = 0.01), CMV infection (OR 3.6; P = 0.02), liposomal amphotericin B (OR 8.06; P = 0.05) and IV voriconazole/posaconazole (OR 13.0; P = 0.003) were predictors of nephrotoxicity. Creatinine concentration was significantly higher at EOT (1.16 ± 0.95 mg/dL) compared with baseline (0.91 ± 0.39 mg/dL; P  & lt; 0.001), but improved by 2 weeks (0.91 ± 0.84 mg/dL; P = 0.007) and 4 weeks (0.96 ± 0.89 mg/dL; P = 0.03) post-EOT. Median viral load significantly declined for patients with adenovirus DNAaemia by EOT (P  & lt; 0.0001) and for patients with CMV DNAaemia by EOT + 4 weeks (P = 0.003), but not for patients with BK virus DNAaemia. Conclusions One in four HCT recipients treated with IV cidofovir developed largely reversible nephrotoxicity. Careful selection of patients and close follow-up of renal function may minimize toxicity.
    Materialart: Online-Ressource
    ISSN: 0305-7453 , 1460-2091
    URL: Article
    DOI: 10.1093/jac/dkab259
    Sprache: Englisch
    Verlag: Oxford University Press (OUP)
    Publikationsdatum: 2021
    ZDB Id: 1467478-6
    SSG: 15,3
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 6
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    Immune monitoring-guided vs fixed duration of antiviral prophylaxis against cytomegalovirus in solid-organ transplant recipients. A Multicenter, Randomized Clinical Trial
    Oxford University Press (OUP) ; 2023
    In:  Clinical Infectious Diseases ( 2023-09-22)
    Details
    In: Clinical Infectious Diseases, Oxford University Press (OUP), ( 2023-09-22)
    Kurzfassung: The use of assays detecting cytomegalovirus (CMV)-specific T-cell-mediated immunity may individualize the duration of antiviral prophylaxis in transplant recipients. Methods In this open-label randomized trial, adult kidney and liver transplant recipients from six centers in Switzerland were enrolled if they were CMV-seronegative with seropositive donors or CMV-seropositive receiving anti-thymocyte globulins. Patients were randomized to a duration of antiviral prophylaxis based on immune-monitoring (intervention) or a fixed duration (control). Patients in the control group were planned to receive 180 days (CMV-seronegative) or 90 days (CMV-seropositive) of valganciclovir. Patients were assessed monthly with a CMV-specific interferon gamma release assay (T-Track® CMV); prophylaxis in the intervention group was stopped if the assay was positive. The primary outcomes were the proportion of patients with clinically significant CMV infection and reduction in days of prophylaxis. Between-group differences were adjusted for CMV serostatus. Results Overall, 193 patients were randomized (92 in the immune-monitoring and 101 in the control group) of which 185 had evaluation of the primary endpoint (87 and 98 patients, respectively). Clinically significant CMV infection occurred in 26/87 (adjusted percentage, 30.9%) in the immune-monitoring group and in 32/98 (adjusted percentage, 31.1%) in the control group (adjusted risk difference -0.1, 95%CI -13.0%, 12.7%; p = 0.064). The duration of antiviral prophylaxis was shorter in the immune-monitoring group (adjusted difference -26.0 days, 95%-CI -41.1 to -10.8 days, p  & lt; 0.001). Conclusions Immune monitoring resulted in a significant reduction of antiviral prophylaxis, but we were unable to establish noninferiority of this approach on the co-primary endpoint of CMV infection.
    Materialart: Online-Ressource
    ISSN: 1058-4838 , 1537-6591
    URL: Article
    DOI: 10.1093/cid/ciad575
    RVK:
    XA 10000
    Sprache: Englisch
    Verlag: Oxford University Press (OUP)
    Publikationsdatum: 2023
    ZDB Id: 2002229-3
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  • 7
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    Atypical pulmonary phaeohyphomycosis due to Aureobasidium spp. – case report and brief literature review
    SMW Supporting Association ; 2022
    In:  Swiss Medical Weekly Vol. 152, No. 4950 ( 2022-12-06), p. 40011-
    Details
    In: Swiss Medical Weekly, SMW Supporting Association, Vol. 152, No. 4950 ( 2022-12-06), p. 40011-
    Kurzfassung: We report on a case of probable invasive Auerobasidium spp. pulmonary infection in a patient with myelodysplastic syndrome. The patient was successfully treated with liposomal amphotericin B monotherapy, with transition to orally administered isavuconazole. This case shows an atypical initial radiological presentation with diffuse ground-glass opacities, as previously demonstrated in cases of Aureobasidium spp. hypersensitivity pneumonitis. Moreover this case further highlights the difficulties associated with the diagnosis and complexity in the management of Aureobasidium spp. infections.
    Materialart: Online-Ressource
    ISSN: 1424-3997
    URL: Article
    DOI: 10.57187/smw.2022.40011
    Sprache: Unbekannt
    Verlag: SMW Supporting Association
    Publikationsdatum: 2022
    ZDB Id: 2031164-3
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 8
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    Letermovir Primary Prophylaxis in High-Risk Hematopoietic Cell Transplant Recipients: A Matched Cohort Study
    MDPI AG ; 2021
    In:  Vaccines Vol. 9, No. 4 ( 2021-04-12), p. 372-
    Details
    In: Vaccines, MDPI AG, Vol. 9, No. 4 ( 2021-04-12), p. 372-
    Kurzfassung: Background: Real-life data on the administration of letermovir as cytomegalovirus (CMV) primary prophylaxis after allogeneic hematopoietic cell transplantation (HCT) remain limited. Methods: We conducted a retrospective single-center matched cohort study, comparing consecutive high-risk allogeneic HCT recipients (cases) receiving primary prophylaxis with letermovir and untreated matched historical controls, during a study period of 180 days. The primary outcome was the incidence of clinically significant (cs) CMV infection. Secondary outcomes included duration and costs of CMV-antiviral treatments, hospital resource utilization, hematology and laboratory parameters. Results: Letermovir prophylaxis decreased csCMV infection incidence from 82.7% (controls) to 34.5% (cases; p-value 〈 0.0001). Controls were more likely to have 〉 1 episode of csCMV infection (59.6%) compared to cases (11.5%; p-value 〈 0.0001). Letermovir was associated with: shorter overall CMV-associated treatment duration (49 days vs. 77.8 days; p-value: 0.02) and a trend for lower costs of CMV-associated treatments ($4096 vs. $9736; p-value: 0.07) and reduced length of stay (44.8 days vs. 59.8 days; p-value: 0.16). Letermovir administration was associated with significantly shorter duration (27.3 days vs. 57.1 days; p-value: 0.008) and lower costs ($1089 vs. $2281; p-value: 0.008) of valganciclovir treatment. Compared to controls, higher platelet counts were observed in cases (138 G/L vs. 92 G/L; p-value: 0.03) and renal function was improved (94 mL/min/1.73 m2 vs. 74 mL/min/1.73 m2; p-value: 0.006). Conclusions: Primary anti-CMV letermovir prophylaxis decreased the incidence of csCMV infection and the administration of CMV-associated treatments and costs, particularly those associated with valganciclovir. An effect of letermovir on platelet reconstitution and renal function of csCMV post-HCT was observed and needs further investigation.
    Materialart: Online-Ressource
    ISSN: 2076-393X
    URL: Article
    DOI: 10.3390/vaccines9040372
    Sprache: Englisch
    Verlag: MDPI AG
    Publikationsdatum: 2021
    ZDB Id: 2703319-3
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 9
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    Real-World Experience of Voriconazole Prophylaxis in Allogeneic Hematopoietic Cell Transplant Recipients: A Single-Center Study
    Oxford University Press (OUP) ; 2017
    In:  Open Forum Infectious Diseases Vol. 4, No. suppl_1 ( 2017-10-01), p. S76-S77
    Details
    In: Open Forum Infectious Diseases, Oxford University Press (OUP), Vol. 4, No. suppl_1 ( 2017-10-01), p. S76-S77
    Kurzfassung: High rates of discontinuation of voriconazole (VCZ) antifungal prophylaxis (AFP) due to toxicities have been reported from single centers in allogeneic hematopoietic (allo-HCT) recipients. We sought to describe (i) adherence to AFP guidelines and (ii) reasons for premature VCZ discontinuation (D/C). Methods Retrospective review of 215 adult allo-HCT recipients from September 1, 2014–December 31, 2015 at our center. Per standards of care (SOC), patients received micafungin from Day 2 post-allo-HCT, then switched to VCZ by D7 unless contraindicated, and remained on AFP until cessation of immunosuppression or D100 for high-risk patients. AFP modification, D/C and treatment emergent adverse events (TEAE) regardless of causality were captured through D100. Standard definitions were used for invasive fungal infections (IFI). Results Of 215 patients, 42 had contraindications to VCZ at baseline. Of 173 patients included in the analysis, 65 (37.6%) received ex vivo T-cell depleted (TCD) peripheral blood (PB), 15% cord and 47.4% conventional PB or marrow allografts. All TCD recipients received myeloablative conditioning (MA) and all cord recipients received reduced intensity conditioning (RIC). For conventional transplant, 65.9 and 26.8% of the patients received RIC and MA, respectively. One hundred and sixty-eight (97%) patients had normal liver function tests (LFT) at VCZ initiation. One hundred and twenty-nine (74.6%) patients started VCZ by D7 and 95% started by D15. Median duration of VCZ AFP was 68D (IQR 22–91). Abnormal LFTs was the most frequently encountered TEAE (42/58, 72%), followed by neurologic/visual TEAE (11/58, 19%) leading to VCZ D/C. Median time to VCZ D/C due to neurologic/visual TEAE (4D, IQR 4–9) was significantly shorter than abnormal LFTs (25D, IQR 16–42) (P & lt; 0.05). Eight (5%) breakthrough proven/probable IFIs were observed by D180, without significant difference based on transplant types or AFP duration. Duration and reasons for VCZ D/C were shown in Table 1 by HCT type. Conclusion 75% of the patients started VCZ per SOC and 95% by D15. Most TEAE leading to VCZ D/C were abnormal LFTs in all HCT types, and most commonly in cord HCT. 3) Neurologic/visual TEAE were similar across types. Rates of IFI were 3–4% in CONV and TCD and 12% in UCB. Disclosures Y. T. Huang, Merck & Co.: Grant Investigator, Research grant. M. A. Perales, Merck: Consultant, Grant Investigator and Investigator, Consulting fee and Research grant. Astella: Consultant, Grant Investigator and Investigator, Consulting fee and Research grant. G. Papanicolaou, Astellas Pharma: Consultant and Grant Investigator, Consulting fee, Research grant and Research support. Merck & Co: DSC member and Investigator, Consulting fee, Research grant and Research support
    Materialart: Online-Ressource
    ISSN: 2328-8957
    URL: Article
    DOI: 10.1093/ofid/ofx163.014
    Sprache: Englisch
    Verlag: Oxford University Press (OUP)
    Publikationsdatum: 2017
    ZDB Id: 2757767-3
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  • 10
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    Safety and Efficacy of Intermittent Intravenous Administration of High-Dose Micafungin
    Oxford University Press (OUP) ; 2015
    In:  Open Forum Infectious Diseases Vol. 2, No. suppl_1 ( 2015-12-09)
    Details
    In: Open Forum Infectious Diseases, Oxford University Press (OUP), Vol. 2, No. suppl_1 ( 2015-12-09)
    Materialart: Online-Ressource
    ISSN: 2328-8957
    URL: Article
    DOI: 10.1093/ofid/ofv131.140
    Sprache: Englisch
    Verlag: Oxford University Press (OUP)
    Publikationsdatum: 2015
    ZDB Id: 2757767-3
    Standort Signatur Einschränkungen Verfügbarkeit
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