Browsing by Author "Buchheidt, Dieter"

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    Immune Parameters for Diagnosis and Treatment Monitoring in Invasive Mold Infection.
    (Journal of fungi (Basel, Switzerland), 2019-12) Jenks, Jeffrey D; Rawlings, Stephen A; Garcia-Vidal, Carol; Koehler, Philipp; Mercier, Toine; Prattes, Juergen; Lass-Flörl, Cornelia; Martin-Gomez, M Teresa; Buchheidt, Dieter; Pagano, Livio; Gangneux, Jean-Pierre; van de Veerdonk, Frank L; Netea, Mihai G; Carvalho, Agostinho; Hoenigl, Martin
    Infections caused by invasive molds, including Aspergillus spp., can be difficult to diagnose and remain associated with high morbidity and mortality. Thus, early diagnosis and targeted systemic antifungal treatment remains the most important predictive factor for a successful outcome in immunocompromised individuals with invasive mold infections. Diagnosis remains difficult due to low sensitivities of diagnostic tests including culture and other mycological tests for mold pathogens, particularly in patients on mold-active antifungal prophylaxis. As a result, antifungal treatment is rarely targeted and reliable markers for treatment monitoring and outcome prediction are missing. Thus, there is a need for improved markers to diagnose invasive mold infections, monitor response to treatment, and assist in determining when antifungal therapy should be escalated, switched, or can be stopped. This review focuses on the role of immunologic markers and specifically cytokines in diagnosis and treatment monitoring of invasive mold infections.
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    (New) Methods for Detection of Aspergillus fumigatus Resistance in Clinical Samples.
    (Current fungal infection reports, 2019-09) Jenks, Jeffrey D; Spiess, Birgit; Buchheidt, Dieter; Hoenigl, Martin

    Purpose of review

    The incidence of invasive aspergillosis has increased substantially over the past few decades, accompanied by a change in susceptibility patterns of Aspergillus fumigatus with increasing resistance observed against triazole antifungals, including voriconazole and isavuconazole, the most commonly used antifungal agents for the disease. Culture-based methods for determining triazole resistance are still the gold standard but are time consuming and lack sensitivity. We sought to provide an update on non-culture-based methods for detecting resistance patterns to Aspergillus.

    Recent findings

    New molecular-based approaches for detecting triazole resistance to Aspergillus, real-time polymerase chain reaction (PCR) to detect mutations to the Cyp51A protein, have been developed which are able to detect most triazole-resistant A. fumigatus strains in patients with invasive aspergillosis.

    Summary

    Over the last few years, a number of non-culture-based methods for molecular detection of Aspergillus triazole resistance have been developed that may overcome some of the limitations of culture. These molecular methods are therefore of high epidemiological and clinical relevance, mainly in immunocompromised patients with hematological malignancies, where culture has particularly limited sensitivity. These assays are now able to detect most triazole-resistant Aspergillus fumigatus strains. Given that resistance rates vary, clinical utility for these assays still depends on regional resistance patterns.
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    Performance of the Bronchoalveolar Lavage Fluid Aspergillus Galactomannan Lateral Flow Assay With Cube Reader for Diagnosis of Invasive Pulmonary Aspergillosis: A Multicenter Cohort Study.
    (Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2021-10) Jenks, Jeffrey D; Prattes, Juergen; Frank, Johanna; Spiess, Birgit; Mehta, Sanjay R; Boch, Tobias; Buchheidt, Dieter; Hoenigl, Martin

    Background

    The Aspergillus Galactomannan Lateral Flow Assay (LFA) is a rapid test for the diagnosis of invasive aspergillosis (IA) that has been almost exclusively evaluated in patients with hematologic malignancies. An automated digital cube reader that allows for quantification of results has recently been added to the test kits.

    Methods

    We performed a retrospective multicenter study on bronchoalveolar lavage fluid (BALF) samples obtained from 296 patients with various underlying diseases (65% without underlying hematological malignancy) who had BALF galactomannan (GM) ordered between 2013 and 2019 at the University of California, San Diego, the Medical University of Graz, Austria, and the Mannheim University Hospital, Germany.

    Results

    Cases were classified as proven (n = 2), probable (n = 56), putative (n = 30), possible (n = 45), and no IA (n = 162). The LFA showed an area under the curve (AUC) of 0.865 (95% confidence interval [CI] .815-.916) for differentiating proven/probable or putative IA versus no IA, with a sensitivity of 74% and a specificity of 83% at an optical density index cutoff of 1.5. After exclusion of GM as mycological criterion for case classification, diagnostic performance of the LFA was highly similar to GM testing (AUC 0.892 vs 0.893, respectively). LFA performance was consistent across different patient cohorts and centers.

    Conclusions

    In this multicenter study the LFA assay from BALF demonstrated good diagnostic performance for IA that was consistent across patient cohorts and locations. The LFA may serve a role as a rapid test that may replace conventional GM testing in settings where GM results are not rapidly available.
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    Reply to Mikulska et al.
    (Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2021-10) Jenks, Jeffrey D; Prattes, Juergen; Buchheidt, Dieter; Hoenigl, Martin
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    Spotlight on isavuconazole in the treatment of invasive aspergillosis and mucormycosis: design, development, and place in therapy.
    (Drug design, development and therapy, 2018-01) Jenks, Jeffrey D; Salzer, Helmut Jf; Prattes, Juergen; Krause, Robert; Buchheidt, Dieter; Hoenigl, Martin
    In recent decades, important advances have been made in the diagnosis and treatment of invasive aspergillosis (IA) and mucormycosis. One of these advances has been the introduction of isavuconazole, a second-generation broad spectrum triazole with a favorable pharmacokinetic and safety profile and few drug-drug interactions. Phase III trials in patients with IA and mucormycosis demonstrated that isavuconazole has similar efficacy to voriconazole for the treatment of IA (SECURE trial) and liposomal amphotericin B for the treatment of mucormycosis (VITAL trial with subsequent case-control analysis) and a favorable safety profile with significantly fewer ocular, hepatobiliary, and skin and soft tissue adverse events compared to voriconazole. As a result, recent IA guidelines recommend isavuconazole (together with voriconazole) as gold standard treatment for IA in patients with underlying hematological malignancies. In contrast to liposomal amphotericin B, isavuconazole can be safely administered in patients with reduced renal function and is frequently used for the treatment of mucormycosis in patients with reduced renal function. Updated guidelines on mucormycosis are needed to reflect the current evidence and give guidance on the use of isavuconazole for mucormycosis. Studies are needed to evaluate the role of isavuconazole for 1) anti-mold prophylaxis in high-risk patients, 2) salvage treatment for IA and mucormycosis, and 3) treatment for other mold infections such as Scedosporium apiospermum.