Browsing by Author "Prattes, Juergen"
Now showing 1 - 13 of 13
Results Per Page
Sort Options
Item Open Access Blood Aspergillus PCR: The Good, the Bad, and the Ugly.(Journal of fungi (Basel, Switzerland), 2020-01) Egger, Matthias; Jenks, Jeffrey D; Hoenigl, Martin; Prattes, JuergenInvasive Aspergillosis (IA) is one of the most common invasive fungal diseases and is accompanied by high morbidity and mortality. In order to maximize patient outcomes and survival, early and rapid diagnosis has been shown to be pivotal. Hence, diagnostic tools aiding and improving the diagnostic process are ambitiously searched for. In this context, polymerase chain reaction (PCR) may represent a potential candidate. Its additional value and benefits in diagnosis have been demonstrated and are scientifically established. Nevertheless, standardized and widespread usage is sparse because several factors influence diagnostic quality and need to be considered in order to optimize diagnostic performance and outcome. In the following review, the current role of PCR in the diagnosis of IA is explored, with special focus on the strengths and limitations of PCR in different settings.Item Open Access Global guideline for the diagnosis and management of rare mould infections: an initiative of the European Confederation of Medical Mycology in cooperation with the International Society for Human and Animal Mycology and the American Society for Microbiology.(The Lancet. Infectious diseases, 2021-08) Hoenigl, Martin; Salmanton-García, Jon; Walsh, Thomas J; Nucci, Marcio; Neoh, Chin Fen; Jenks, Jeffrey D; Lackner, Michaela; Sprute, Rosanne; Al-Hatmi, Abdullah MS; Bassetti, Matteo; Carlesse, Fabianne; Freiberger, Tomas; Koehler, Philipp; Lehrnbecher, Thomas; Kumar, Anil; Prattes, Juergen; Richardson, Malcolm; Revankar, Sanjay; Slavin, Monica A; Stemler, Jannik; Spiess, Birgit; Taj-Aldeen, Saad J; Warris, Adilia; Woo, Patrick CY; Young, Jo-Anne H; Albus, Kerstin; Arenz, Dorothee; Arsic-Arsenijevic, Valentina; Bouchara, Jean-Philippe; Chinniah, Terrence Rohan; Chowdhary, Anuradha; de Hoog, G Sybren; Dimopoulos, George; Duarte, Rafael F; Hamal, Petr; Meis, Jacques F; Mfinanga, Sayoki; Queiroz-Telles, Flavio; Patterson, Thomas F; Rahav, Galia; Rogers, Thomas R; Rotstein, Coleman; Wahyuningsih, Retno; Seidel, Danila; Cornely, Oliver AWith increasing numbers of patients needing intensive care or who are immunosuppressed, infections caused by moulds other than Aspergillus spp or Mucorales are increasing. Although antifungal prophylaxis has shown effectiveness in preventing many invasive fungal infections, selective pressure has caused an increase of breakthrough infections caused by Fusarium, Lomentospora, and Scedosporium species, as well as by dematiaceous moulds, Rasamsonia, Schizophyllum, Scopulariopsis, Paecilomyces, Penicillium, Talaromyces and Purpureocillium species. Guidance on the complex multidisciplinary management of infections caused by these pathogens has the potential to improve prognosis. Management routes depend on the availability of diagnostic and therapeutic options. The present recommendations are part of the One World-One Guideline initiative to incorporate regional differences in the epidemiology and management of rare mould infections. Experts from 24 countries contributed their knowledge and analysed published evidence on the diagnosis and treatment of rare mould infections. This consensus document intends to provide practical guidance in clinical decision making by engaging physicians and scientists involved in various aspects of clinical management. Moreover, we identify areas of uncertainty and constraints in optimising this management.Item Open Access 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, MartinInfections 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.Item Open Access Novel antifungals and treatment approaches to tackle resistance and improve outcomes of invasive fungal disease(Clinical Microbiology Reviews) Hoenigl, Martin; Arastehfar, Amir; Arendrup, Maiken Cavling; Brüggemann, Roger; Carvalho, Agostinho; Chiller, Tom; Chen, Sharon; Egger, Matthias; Feys, Simon; Gangneux, Jean-Pierre; Gold, Jeremy AW; Groll, Andreas H; Heylen, Jannes; Jenks, Jeffrey D; Krause, Robert; Lagrou, Katrien; Lamoth, Frédéric; Prattes, Juergen; Sedik, Sarah; Wauters, Joost; Wiederhold, Nathan P; Thompson, George RSUMMARY Fungal infections are on the rise, driven by a growing population at risk and climate change. Currently available antifungals include only five classes, and their utility and efficacy in antifungal treatment are limited by one or more of innate or acquired resistance in some fungi, poor penetration into “sequestered” sites, and agent-specific side effect which require frequent patient reassessment and monitoring. Agents with novel mechanisms, favorable pharmacokinetic (PK) profiles including good oral bioavailability, and fungicidal mechanism(s) are urgently needed. Here, we provide a comprehensive review of novel antifungal agents, with both improved known mechanisms of actions and new antifungal classes, currently in clinical development for treating invasive yeast, mold (filamentous fungi), Pneumocystis jirovecii infections, and dimorphic fungi (endemic mycoses). We further focus on inhaled antifungals and the role of immunotherapy in tackling fungal infections, and the specific PK/pharmacodynamic profiles, tissue distributions as well as drug-drug interactions of novel antifungals. Finally, we review antifungal resistance mechanisms, the role of use of antifungal pesticides in agriculture as drivers of drug resistance, and detail detection methods for antifungal resistance.Item Open Access 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, MartinBackground
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.Item Open Access 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, MartinItem Open Access Risk factors and outcome of pulmonary aspergillosis in critically ill coronavirus disease 2019 patients-a multinational observational study by the European Confederation of Medical Mycology.(Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases, 2022-04) Prattes, Juergen; Wauters, Joost; Giacobbe, Daniele Roberto; Salmanton-García, Jon; Maertens, Johan; Bourgeois, Marc; Reynders, Marijke; Rutsaert, Lynn; Van Regenmortel, Niels; Lormans, Piet; Feys, Simon; Reisinger, Alexander Christian; Cornely, Oliver A; Lahmer, Tobias; Valerio, Maricela; Delhaes, Laurence; Jabeen, Kauser; Steinmann, Joerg; Chamula, Mathilde; Bassetti, Matteo; Hatzl, Stefan; Rautemaa-Richardson, Riina; Koehler, Philipp; Lagrou, Katrien; Hoenigl, Martin; ECMM-CAPA Study GroupObjectives
Coronavirus disease 2019 (COVID-19) -associated pulmonary aspergillosis (CAPA) has emerged as a complication in critically ill COVID-19 patients. The objectives of this multinational study were to determine the prevalence of CAPA in patients with COVID-19 in intensive care units (ICU) and to investigate risk factors for CAPA as well as outcome.Methods
The European Confederation of Medical Mycology (ECMM) conducted a multinational study including 20 centres from nine countries to assess epidemiology, risk factors and outcome of CAPA. CAPA was defined according to the 2020 ECMM/ISHAM consensus definitions.Results
A total of 592 patients were included in this study, including 11 (1.9%) patients with histologically proven CAPA, 80 (13.5%) with probable CAPA, 18 (3%) with possible CAPA and 483 (81.6%) without CAPA. CAPA was diagnosed a median of 8 days (range 0-31 days) after ICU admission predominantly in older patients (adjusted hazard ratio (aHR) 1.04 per year; 95% CI 1.02-1.06) with any form of invasive respiratory support (HR 3.4; 95% CI 1.84-6.25) and receiving tocilizumab (HR 2.45; 95% CI 1.41-4.25). Median prevalence of CAPA per centre was 10.7% (range 1.7%-26.8%). CAPA was associated with significantly lower 90-day ICU survival rate (29% in patients with CAPA versus 57% in patients without CAPA; Mantel-Byar p < 0.001) and remained an independent negative prognostic variable after adjusting for other predictors of survival (HR 2.14; 95% CI 1.59-2.87, p ≤ 0.001).Conclusion
Prevalence of CAPA varied between centres. CAPA was significantly more prevalent among older patients, patients receiving invasive ventilation and patients receiving tocilizumab, and was an independent strong predictor of ICU mortality.Item Open Access Serum Lateral Flow assay with digital reader for the diagnosis of invasive pulmonary aspergillosis: A two-centre mixed cohort study.(Mycoses, 2021-10) Hoenigl, Martin; Egger, Matthias; Boyer, Johannes; Schulz, Eduard; Prattes, Juergen; Jenks, Jeffrey DBackground
Detection of galactomannan (GM) from bronchoalveolar lavage fluid (BALF) or serum is broadly used for diagnosis of invasive aspergillosis (IA), although the sensitivity of GM from serum is lower in non-neutropenic patients. We evaluated the Aspergillus galactomannan Lateral Flow assay (LFA) with digital readout from serum in a mixed cohort of patients.Methods
We performed a retrospective two-centre study evaluating the LFA from serum of patients with clinical suspicion of IA obtained between 2015 and 2021 at the University of California San Diego and the Medical University of Graz. The sensitivity and specificity was calculated for proven/probable aspergillosis versus no aspergillosis. Correlation with same-sample GM was calculated using Spearman correlation analysis and kappa statistics.Results
In total, 122 serum samples from 122 patients were analysed, including proven IA (n = 1), probable IA or coronavirus-associated pulmonary aspergillosis (CAPA) (n = 27), and no IA/CAPA/non-classifiable (n = 94). At a 0.5 ODI cut-off, the sensitivity and specificity of the LFA was 78.6% and 80.5%. Spearman correlation analysis showed a strong correlation between serum LFA ODI and serum GM ODI (ρ 0.459, p < .0001). Kappa was 0.611 when both LFA and GM were used with a 0.5 ODI cut-off, showing substantial agreement (p < .001).Discussion
The LFA with digital read out from serum showed good performance for the diagnosis of probable/proven aspergillosis, with substantial agreement to GM from serum. Like the LFA from BALF, the LFA from serum may serve as a more rapid test compared to conventional GM, particularly in settings where GM is not readily available.Item Open Access Social determinants of health as drivers of fungal disease(eClinicalMedicine, 2023-12-01) Jenks, Jeffrey D; Prattes, Juergen; Wurster, Sebastian; Sprute, Rosanne; Seidel, Danila; Oliverio, Matteo; Egger, Matthias; Del Rio, Carlos; Sati, Hatim; Cornely, Oliver A; Thompson, George R; Kontoyiannis, Dimitrios P; Hoenigl, MartinDisparities in social determinants of health (SDOH) play a significant role in causing health inequities globally. The physical environment, including housing and workplace environment, can increase the prevalence and spread of fungal infections. A number of professions are associated with increased fungal infection risk and are associated with low pay, which may be linked to crowded and sub-optimal living conditions, exposure to fungal organisms, lack of access to quality health care, and risk for fungal infection. Those involved and displaced from areas of armed conflict have an increased risk of invasive fungal infections. Lastly, a number of fungal plant pathogens already threaten food security, which will become more problematic with global climate change. Taken together, disparities in SDOH are associated with increased risk for contracting fungal infections. More emphasis needs to be placed on systematic approaches to better understand the impact and reducing the health inequities associated with these disparities.Item Open Access 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, MartinIn 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.Item Open Access The Aspergillus Lateral Flow Assay for the Diagnosis of Invasive Aspergillosis: an Update.(Current fungal infection reports, 2020-01) Jenks, Jeffrey D; Miceli, Marisa H; Prattes, Juergen; Mercier, Toine; Hoenigl, MartinPurpose of review
To review the data on the Aspergillus lateral flow assay for the diagnosis of invasive Aspergillosis.Recent findings
Aspergillus spp. cause a wide spectrum of disease with invasive aspergillosis (IA) as its most severe manifestation. Early and reliable diagnosis of disease is crucial to decrease associated morbidity and mortality, and enable prompt initiation of treatment for IA. Most recently, non-culture-based tests, such as Aspergillus galactomannan (GM), have been useful in early identification and treatment of patients with IA. However, cost, turnaround time, and variable performance indifferent populations at risk for IA remain significant drawbacks to the use of this test. Several diagnostic tests for IA have been developed, including the sōna Aspergillus GM Lateral flow assay (GM-LFA) rapid test.Summary
The GM-LFA has shown excellent performance for the diagnosis of IA in patients with hematologic malignancy and may be a viable option for settings where ELISA GM testing is not feasible. Further evaluation of the GM-LFA in the non-hematology setting is ongoing, including in solid organ transplant recipients and patients in the intensive care unit.Item Open Access The Antifungal Pipeline: Fosmanogepix, Ibrexafungerp, Olorofim, Opelconazole, and Rezafungin.(Drugs, 2021-10) Hoenigl, Martin; Sprute, Rosanne; Egger, Matthias; Arastehfar, Amir; Cornely, Oliver A; Krause, Robert; Lass-Flörl, Cornelia; Prattes, Juergen; Spec, Andrej; Thompson, George R; Wiederhold, Nathan; Jenks, Jeffrey DThe epidemiology of invasive fungal infections is changing, with new populations at risk and the emergence of resistance caused by the selective pressure from increased usage of antifungal agents in prophylaxis, empiric therapy, and agriculture. Limited antifungal therapeutic options are further challenged by drug-drug interactions, toxicity, and constraints in administration routes. Despite the need for more antifungal drug options, no new classes of antifungal drugs have become available over the last 2 decades, and only one single new agent from a known antifungal class has been approved in the last decade. Nevertheless, there is hope on the horizon, with a number of new antifungal classes in late-stage clinical development. In this review, we describe the mechanisms of drug resistance employed by fungi and extensively discuss the most promising drugs in development, including fosmanogepix (a novel Gwt1 enzyme inhibitor), ibrexafungerp (a first-in-class triterpenoid), olorofim (a novel dihyroorotate dehydrogenase enzyme inhibitor), opelconazole (a novel triazole optimized for inhalation), and rezafungin (an echinocandin designed to be dosed once weekly). We focus on the mechanism of action and pharmacokinetics, as well as the spectrum of activity and stages of clinical development. We also highlight the potential future role of these drugs and unmet needs.Item Open Access Using Interleukin 6 and 8 in Blood and Bronchoalveolar Lavage Fluid to Predict Survival in Hematological Malignancy Patients With Suspected Pulmonary Mold Infection.(Frontiers in immunology, 2019-01) Rawlings, Stephen A; Heldt, Sven; Prattes, Juergen; Eigl, Susanne; Jenks, Jeffrey D; Flick, Holger; Rabensteiner, Jasmin; Prüller, Florian; Wölfler, Albert; Neumeister, Peter; Strohmaier, Heimo; Krause, Robert; Hoenigl, MartinBackground: Molds and other pathogens induce elevated levels of several cytokines, including interleukin (IL)-6 and IL-8. The objective of this study was to investigate the prognostic value of IL-6 and IL-8 as well as fungal biomarkers in blood and bronchoalveolar lavage fluid (BAL) for overall survival in patients with underlying hematological malignancies and suspected mold infection. Methods: This cohort study included 106 prospectively enrolled adult cases undergoing bronchoscopy. Blood samples were collected within 24 h of BAL sampling and, in a subset of 62 patients, serial blood samples were collected up until 4 days after bronchoscopy. IL-6, IL-8, and other cytokines as well as galactomannan (GM) and β-D-glucan (BDG) were assayed in blood and BAL fluid and associations with overall mortality were assessed at the end of the study using receiver operating characteristic (ROC) curve analysis. Results: Both blood IL-8 (AUC 0.731) and blood IL-6 (AUC 0.699) as well as BAL IL-6 (AUC 0.763) and BAL IL-8 (AUC 0.700) levels at the time of bronchoscopy were predictors of 30-day all-cause mortality. Increasing blood IL-6 levels between bronchoscopy and day four after bronchoscopy were significantly associated with higher 90-day mortality, with similar findings for increasing IL-8 levels. In ROC analysis the difference of blood IL-8 levels between 4 days after bronchoscopy and the day of bronchoscopy had an AUC of 0.829 (95%CI 0.71-0.95; p < 0.001) for predicting 90-day mortality. Conclusions: Elevated levels of IL-6 and IL-8 in blood or BAL fluid at the time of bronchoscopy, and rising levels in blood 4 days following bronchoscopy were predictive of mortality in these patients with underlying hematological malignancy who underwent bronchoscopy for suspected mold infection.