11 results on '"Vonk, Alieke G"'
Search Results
2. The diagnosis and treatment of invasive aspergillosis in Dutch haematology units facing a rapidly increasing prevalence of azole-resistance. A nationwide survey and rationale for the DB-MSG 002 study protocol.
- Author
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Schauwvlieghe AFAD, de Jonge N, van Dijk K, Verweij PE, Brüggemann RJ, Biemond BJ, Bart A, von dem Borne PA, Verbon A, van der Beek MT, Demandt AMP, Oudhuis GJ, Cornelissen JJ, van der Velden WJFM, Span LFR, Kampinga GA, Bruns AH, Vonk AG, Haas PA, Doorduijn JK, and Rijnders BJA
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- Academic Medical Centers, Antifungal Agents pharmacology, Aspergillus fumigatus drug effects, Azoles pharmacology, Chemoprevention methods, Humans, Invasive Pulmonary Aspergillosis prevention & control, Netherlands, Prevalence, Surveys and Questionnaires, Antifungal Agents administration & dosage, Azoles administration & dosage, Disease Management, Drug Resistance, Fungal, Hematologic Neoplasms complications, Invasive Pulmonary Aspergillosis diagnosis, Invasive Pulmonary Aspergillosis drug therapy
- Abstract
Patients with haematological malignancies are at risk for invasive fungal diseases (IFD). A survey was conducted in all Dutch academic haematology centres on their current diagnostic, prophylactic and therapeutic approach towards IFD in the context of azole-resistance. In all 8 centres, a haematologist and microbiologist filled in the questionnaire that focused on different subgroups of haematology patients. Fungal prophylaxis during neutropaenia was directed against Candida and consisted of fluconazole and/or amphotericin B suspension. Mould-active prophylaxis was given to acute myeloid leukaemia patients during chemotherapy in 2 of 8 centres. All centres used azole prophylaxis in a subset of patients with graft-versus-host disease. A uniform approach towards the diagnosis and treatment of IFD and in particular azole-resistant Aspergillus fumigatus was lacking. In 2017, all centres agreed to implement a uniform diagnostic and treatment algorithm regarding invasive aspergillosis with a central role for comprehensive diagnostics and PCR-based detection of azole-resistance. This study (DB-MSG 002) will re-evaluate this algorithm when 280 patients have been treated. A heterogeneous approach towards antifungal prophylaxis, diagnosis and treatment was apparent in the Netherlands. Facing triazole-resistance, consensus was reached on the implementation of a uniform diagnostic approach in all 8 centres., (© 2018 The Authors. Mycoses Published by Blackwell Verlag GmbH.)
- Published
- 2018
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3. Echinocandin to fluconazole step-down therapy in critically ill patients with invasive, susceptible Candida albicans infections.
- Author
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van der Geest PJ, Rijnders BJ, Vonk AG, and Groeneveld AB
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- Administration, Intravenous, Adult, Aged, Anidulafungin, Antifungal Agents administration & dosage, Antifungal Agents classification, Caspofungin, Critical Illness, Echinocandins administration & dosage, Female, Fluconazole administration & dosage, Humans, Intensive Care Units, Lipopeptides administration & dosage, Lipopeptides therapeutic use, Male, Micafungin, Middle Aged, Multivariate Analysis, Retrospective Studies, Antifungal Agents therapeutic use, Candidiasis, Invasive drug therapy, Echinocandins therapeutic use, Fluconazole therapeutic use
- Abstract
Invasive Candida spp. infections are increasingly diagnosed in critically ill patients. For initial treatment, an echinocandin is recommended with a possible step-down to fluconazole when the patients' condition is improving and the isolate appears susceptible, but there are no data to support such policy. We studied the safety and efficacy of step-down therapy in critically ill patients with culture proven deep seated or bloodstream infections by C. albicans susceptible to fluconazole. All patients admitted into the intensive care unit from January 2010 to December 2014, who had a culture proven invasive C. albicans infection and received initial treatment with an echinocandin for at least 4 days were included. Data on patient characteristics, treatment and vital outcomes were assessed. Of the 56 patients, 32 received step-down fluconazole therapy, at median day 5, whereas the echinocandin was continued in the other 24. No differences where seen in baseline characteristics or risk factors for invasive C. albicans infection between the two groups. Response rates were similar and no difference where seen in 28-day or 90-day mortality between the groups. Step-down therapy to fluconazole may be safe and effective in critically ill patients with invasive infections by C. albicans, susceptible to fluconazole, who have clinically improved as early as 4 days after start of treatment with an echinocandin., (© 2015 Blackwell Verlag GmbH.)
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- 2016
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4. Validation of a new Aspergillus real-time PCR assay for direct detection of Aspergillus and azole resistance of Aspergillus fumigatus on bronchoalveolar lavage fluid.
- Author
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Chong GL, van de Sande WW, Dingemans GJ, Gaajetaan GR, Vonk AG, Hayette MP, van Tegelen DW, Simons GF, and Rijnders BJ
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- Aspergillus drug effects, Cytochrome P-450 Enzyme System genetics, Female, Fungal Proteins genetics, Humans, Invasive Pulmonary Aspergillosis diagnosis, Invasive Pulmonary Aspergillosis microbiology, Male, Molecular Diagnostic Techniques methods, Mutant Proteins genetics, Mutation, Missense, Predictive Value of Tests, Retrospective Studies, Sensitivity and Specificity, Antifungal Agents pharmacology, Aspergillus isolation & purification, Azoles pharmacology, Bronchoalveolar Lavage Fluid microbiology, Microbiological Techniques methods, Multiplex Polymerase Chain Reaction methods, Real-Time Polymerase Chain Reaction methods
- Abstract
Azole resistance in Aspergillus fumigatus is increasingly reported. Here, we describe the validation of the AsperGenius, a new multiplex real-time PCR assay consisting of two multiplex real-time PCRs, one that identifies the clinically relevant Aspergillus species, and one that detects the TR34, L98H, T289A, and Y121F mutations in CYP51A and differentiates susceptible from resistant A. fumigatus strains. The diagnostic performance of the AsperGenius assay was tested on 37 bronchoalveolar lavage (BAL) fluid samples from hematology patients and 40 BAL fluid samples from intensive care unit (ICU) patients using a BAL fluid galactomannan level of ≥1.0 or positive culture as the gold standard for detecting the presence of Aspergillus. In the hematology and ICU groups combined, there were 22 BAL fluid samples from patients with invasive aspergillosis (IA) (2 proven, 9 probable, and 11 nonclassifiable). Nineteen of the 22 BAL fluid samples were positive, according to the gold standard. The optimal cycle threshold value for the presence of Aspergillus was <36. Sixteen of the 19 BAL fluid samples had a positive PCR (2 Aspergillus species and 14 A. fumigatus samples). This resulted in a sensitivity, specificity, and positive and negative predictive values of 88.9%, 89.3%, 72.7%, and 96.2%, respectively, for the hematology group and 80.0%, 93.3%, 80.0%, and 93.3%, respectively, in the ICU group. The CYP51A real-time PCR confirmed 12 wild-type and 2 resistant strains (1 TR34-L98H and 1 TR46-Y121F-T289A mutant). Voriconazole therapy failed for both patients. The AsperGenius multiplex real-time PCR assay allows for sensitive and fast detection of Aspergillus species directly from BAL fluid samples. More importantly, this assay detects and differentiates wild-type from resistant strains, even if BAL fluid cultures remain negative., (Copyright © 2015, American Society for Microbiology. All Rights Reserved.)
- Published
- 2015
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5. Voriconazole or amphotericin B as primary therapy yields distinct early serum galactomannan trends related to outcomes in invasive aspergillosis.
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Chai LY, Kullberg BJ, Earnest A, Johnson EM, Teerenstra S, Vonk AG, Schlamm HT, Herbrecht R, Netea MG, and Troke PF
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- Aspergillosis diagnosis, Aspergillosis microbiology, Aspergillosis mortality, Biomarkers blood, Female, Galactose analogs & derivatives, Hematologic Neoplasms diagnosis, Hematologic Neoplasms drug therapy, Hematologic Neoplasms microbiology, Hematologic Neoplasms mortality, Humans, Male, Survival Analysis, Treatment Outcome, Voriconazole, Amphotericin B therapeutic use, Antifungal Agents therapeutic use, Aspergillosis drug therapy, Fungal Polysaccharides blood, Mannans blood, Pyrimidines therapeutic use, Triazoles therapeutic use
- Abstract
An improved number of anti-fungal drugs are currently available for the treatment of invasive aspergillosis (IA). While serial galactomannan index (GMI) measurement can be used to monitor response to treatment, the extent to which different anti-fungal regimens can affect galactomannan levels is unknown. In 147 IA patients receiving either voriconazole (VCZ) or conventional amphotericin B (CAB) in a multicentre clinical trial, we performed post-hoc analyses of GMI trends in relation to outcomes. The generalized estimation equations approach was used to estimate changes in the effect size for GMI over time within patients. Patients who received VCZ primary therapy and had good treatment response 12 weeks later showed earlier decreases in GMI values at Week 1 and Week 2 (p = 0.001 and 0.046 respectively) as compared to patients who only received CAB. At end-of-randomized therapy (EORT), which was a pre-set secondary assessment point for all patients who switched from randomized primary (CAB or VCZ) to an alternative anti-fungal drug, treatment failure was associated with increasing GMI at Weeks 1 and 2 in CAB-primary treated patients (p = 0.022 and 0.046 respectively). These distinct trends highlight the variations in GMI kinetics with the use of different anti-fungal drugs and their implications in relation to IA treatment response.
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- 2014
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6. An elevated pro-inflammatory cytokine response is linked to development of amphotericin B-induced nephrotoxicity.
- Author
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Chai LY, Netea MG, Tai BC, Khin LW, Vonk AG, Teo BW, Schlamm HT, Herbrecht R, Donnelly JP, Troke PF, and Kullberg BJ
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- Adult, Aged, Amphotericin B administration & dosage, Antifungal Agents administration & dosage, Female, Humans, Male, Middle Aged, Serum chemistry, Acute Kidney Injury chemically induced, Acute Kidney Injury immunology, Amphotericin B adverse effects, Antifungal Agents adverse effects, Interleukin-10 blood, Interleukin-6 blood, Interleukin-8 blood
- Abstract
Objectives: The underlying mechanism for amphotericin B-induced acute kidney injury (AKI) remains poorly understood and may be immunologically mediated. We assessed whether the development of nephrotoxicity is linked to a distinct cytokine profile in patients receiving amphotericin B deoxycholate (AmBD)., Patients and Methods: In 58 patients who received AmBD, circulating serum interleukin (IL)-6, IL-8 and IL-10 were measured at baseline, week 1 and week 2 of antifungal treatment and correlated to the development of renal impairment. The Cox proportional hazards model approach was adopted for analysis., Results: The P value was 0.026 for the overall effect of IL-6 on time to development of AKI. An increasing or non-receding IL-6 trend by week 1 of AmBD treatment (followed by a decreasing or non-receding IL-6 trend from week 1 to week 2) correlated with an increased likelihood of nephrotoxicity [hazard ratio (HR) 6.93, P value 0.005 and HR 3.46, P value 0.035, respectively]. Similarly, persistently increasing IL-8 levels were linked to a 3.84-fold increased likelihood of AKI., Conclusions: In patients receiving AmBD, persistence of an elevated pro-inflammatory cytokine milieu is associated with a predisposition to drug-related kidney injury.
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- 2013
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7. Host defence against disseminated Candida albicans infection and implications for antifungal immunotherapy.
- Author
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Vonk AG, Netea MG, van der Meer JW, and Kullberg BJ
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- Adjuvants, Immunologic economics, Animals, Candidiasis immunology, Candidiasis prevention & control, Complement System Proteins immunology, Dendritic Cells immunology, Drug Therapy, Combination, Fluconazole therapeutic use, Fungal Vaccines administration & dosage, Granulocyte Colony-Stimulating Factor therapeutic use, Humans, Immunity, Cellular drug effects, Immunity, Innate drug effects, Interferon-gamma therapeutic use, Killer Cells, Natural immunology, Phagocytes immunology, Randomized Controlled Trials as Topic economics, Receptors, Pattern Recognition immunology, Recombinant Proteins, Th1 Cells immunology, Th2 Cells immunology, Adjuvants, Immunologic therapeutic use, Antifungal Agents therapeutic use, Candida albicans immunology, Candidiasis drug therapy
- Abstract
The different manifestations of Candida albicans infection are dictated by an underlying defect in the immune response of the host. Protective immunity to disseminated candidiasis, the manifestation of C. albicans infection discussed in this review, has traditionally been ascribed to innate immunity with emphasis on the role of granulocytes. Lately, however, immunological studies have learned that host defence against disseminated candidiasis is based on a complex interplay between innate and cell-mediated immunity. Despite the availability of new antifungal agents, mortality associated with disseminated C. albicans infection remains high. Immunotherapy that augments host defence is an important strategic option in the battle against disseminated candidiasis. Here, the authors review the chronological events in the pathogenesis of disseminated candidiasis that aid in predicting the impact of existing immunotherapy and the development of future immunomodulating strategies.
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- 2006
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8. Treatment of intra-abdominal abscesses caused by Candida albicans with antifungal agents and recombinant murine granulocyte colony-stimulating factor.
- Author
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Vonk AG, Netea MG, van Krieken JH, Verweij PE, van der Meer JW, and Kullberg BJ
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- Adjuvants, Immunologic pharmacokinetics, Adjuvants, Immunologic therapeutic use, Amphotericin B pharmacokinetics, Amphotericin B therapeutic use, Animals, Antifungal Agents pharmacokinetics, Cytokines biosynthesis, Female, Fluconazole therapeutic use, Granulocyte Colony-Stimulating Factor pharmacokinetics, Lymphocytes drug effects, Lymphocytes immunology, Mice, Mice, Inbred CBA, Microbial Sensitivity Tests, Recombinant Proteins pharmacokinetics, Recombinant Proteins therapeutic use, Spleen cytology, Spleen drug effects, Treatment Outcome, Abdominal Abscess drug therapy, Abdominal Abscess microbiology, Antifungal Agents therapeutic use, Candida albicans drug effects, Granulocyte Colony-Stimulating Factor therapeutic use
- Abstract
The aim of the present study was to assess the influence of immunomodulation of host defense with recombinant murine granulocyte colony-stimulating factor (rmG-CSF) on intra-abdominal abscesses caused by Candida albicans. Mice received prophylaxis or therapy with 1 microg of rmG-CSF/day in the presence or absence of antifungal treatment consisting of amphotericin B (0.75 mg/kg of body weight/day) or fluconazole (50 mg/kg/day). The number of Candida CFU in abscesses was significantly reduced (P<0.05) in mice receiving rmG-CSF prophylaxis (day -1 or day -1 through 2) compared with controls on day 8 of infection. Administration of rmG-CSF therapy alone (for 5 days starting on day 4 of infection) had no influence on the number of Candida CFU in abscesses. Amphotericin B treatment was significantly more effective than fluconazole treatment (3.41 log CFU/abscesses; 95% confidence interval [CI], 3.17 log CFU/abscesses; 3.65 versus 3.90 log CFU/abscesses; 95% CI, 3.66 log CFU/abscesses, 4.16 log CFU/abscesses; P<0.05). Therapeutic administration of rmG-CSF in conjunction with an antifungal agent showed a tendency towards a further reduction of Candida CFU in abscesses than antifungal treatment only. In conclusion, in this experimental model of intra-abdominal Candida abscesses, rmG-CSF administration did not have a detrimental influence on the course of infection. Amphotericin B treatment was most effective, and additional rmG-CSF therapy did not antagonize the effect of antifungal treatment. In contrast, addition of rmG-CSF therapy to antifungal treatment might further enhance the beneficial effect of the antifungal agent.
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- 2003
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9. Periocular tinea caused by zoonotic Trichophyton benhamiae
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Sips, Gregorius J, Lekkerkerk, Wouter S N, Boddé, Elisabeth, Broens, Els M, Vonk, Alieke G, Thio, Hok Bing, Klinische infectiologie en microb. lab., dI&I I&I-4, Klinische infectiologie en microb. lab., dI&I I&I-4, Medical Microbiology & Infectious Diseases, and Dermatology
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medicine.medical_specialty ,Antifungal Agents ,Bacterial Zoonoses ,business.industry ,Arthrodermataceae ,Middle Aged ,Dermatology ,Infectious Diseases ,Tinea ,SDG 3 - Good Health and Well-being ,Taverne ,medicine ,Animals ,Humans ,Female ,business ,Terbinafine ,Trichophyton benhamiae - Published
- 2021
10. Paradoxal Trends in Azole-Resistant Aspergillus fumigatus in a National Multicenter Surveillance Program, the Netherlands, 2013-2018.
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Lestrade, Pieter P. A., Buil, Jochem B., van der Beek, Martha T., Kuijper, Ed J., van Dijk, Karin, Kampinga, Greetje A., Rijnders, Bart J. A., Vonk, Alieke G., de Greeff, Sabine C., Schoffelen, Annelot F., van Dissel, Jaap, Meis, Jacques F., Melchers, Willem J. G., and Verweij, Paul E.
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ANTIFUNGAL agents ,PROTEINS ,RESEARCH ,HETEROCYCLIC compounds ,RESEARCH methodology ,MEDICAL cooperation ,EVALUATION research ,COMPARATIVE studies ,DRUG resistance in microorganisms ,ASPERGILLUS ,MICROBIAL sensitivity tests ,PHARMACODYNAMICS - Abstract
We investigated the prevalence of azole resistance of Aspergillus fumigatus isolates in the Netherlands by screening clinical A. fumigatus isolates for azole resistance during 2013-2018. We analyzed azole-resistant isolates phenotypically by in vitro susceptibility testing and for the presence of resistance mutations in the Cyp51A gene. Over the 6-year period, 508 (11%) of 4,496 culture-positive patients harbored an azole-resistant isolate. Resistance frequency increased from 7.6% (95% CI 5.9%-9.8%) in 2013 (58/760 patients) to 14.7% (95% CI 12.3%-17.4%) in 2018 (112/764 patients) (p = 0.0001). TR34/L98H (69%) and TR46/Y121F/T289A (17%) accounted for 86% of Cyp51A mutations. However, the mean voriconazole MIC of TR34/L98H isolates decreased from 8 mg/L (2013) to 2 mg/L (2018), and the voriconazole-resistance frequency was 34% lower in 2018 than in 2013 (p = 0.0001). Our survey showed changing azole phenotypes in TR34/L98H isolates, which hampers the use of current PCR-based resistance tests. [ABSTRACT FROM AUTHOR]
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- 2020
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11. Early Proinflammatory Cytokines and C-Reactive Protein Trends as Predictors of Outcome in Invasive Aspergillosis.
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Chai, Louis Y. A., Netea, Mihai G., Teerenstra, Steven, Earnest, Arul, Vonk, Alieke G., Schlamm, Haran T., Herbrecht, Raoul, Troke, Peter F., and Kullberg, Bart-Jan
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C-reactive protein ,CYTOKINES ,ASPERGILLOSIS ,IMMUNE response ,INTERLEUKINS ,ANTIFUNGAL agents - Abstract
Background. Monitoring treatment response in invasive aspergillosis is challenging, because an immunocompromised host may not exhibit reliable symptoms and clinical signs. Cytokines play a pivotal role in mediating host immune response to infection; therefore, the profiling of biomarkers may be an appropriate surrogate for disease status. Methods. We studied, in a cohort of 119 patients with invasive aspergillosis who were recruited in a multicenter clinical trial, serum interleukin (IL)-6, IL-8, IL-10, interferon-g, and C-reactive protein (CRP) trends over the first 4 weeks of therapy and correlated these trends to clinical outcome parameters. Results. Circulating IL-6 and CRP levels were high at initiation of therapy and generally showed a downward trend with antifungal treatment. However, subjects with adverse outcomes exhibited a distinct lack of decline in IL-6 and CRP levels at week 1, compared with responders (Pp.02, for both IL-6 and CRP). Nonresponders also had significantly elevated IL-8 levels (P=.001). Conclusions. High initial IL-8 and persistently elevated IL-6, IL-8, and CRP levels after initiation of treatment may be early predictors of adverse outcome in invasive aspergillosis. Cytokine and CRP profiles could be used for early identification of patients with a poor response to antifungal treatment who may benefit from more-aggressive antimicrobial regimens. [ABSTRACT FROM AUTHOR]
- Published
- 2010
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