Martina Tošková
Masaryk University
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Featured researches published by Martina Tošková.
Journal of Medical Microbiology | 2010
Zdenek Racil; Iva Kocmanová; Martina Lengerová; Barbora Weinbergerová; Lucie Burešová; Martina Tošková; Jana Winterová; Shira Timilsina; Isa Rodriguez; Jiri Mayer
We have evaluated the contribution of the 1,3-beta-d-glucan (BG) assay for the screening of invasive fungal infections (IFIs) in patients with haematological malignancies. Serum samples from patients at risk of IFI were collected twice a week and retrospectively tested using the BG assay. BG screening was performed on 1143 samples from 91 patients during 104 anticancer treatment cycles. Proven and probable cases of IFI occurred in 9 (8.7 %) treatment cycles. Depending on the criterion of positivity used (1x >60 pg ml(-1), 1x >80 pg ml(-1), 2x >60 pg ml(-1) or 2x >80 pg ml(-1)) the sensitivity and specificity were 89, 89, 67 and 44 %, and 20, 48, 33 and 56 %, respectively. Although the test was marked as positive in 82, 68, 54 and 45 % of all the treatment cycles, in the majority of cases, these positivities were probably false. The major limit of the BG test was an extremely low positive predictive value (10 to 12 %). We have analysed mucositis, candida colonization, bacteraemia, use of antimicrobials, erythrocyte and thrombocyte filtered blood products, collecting tubes or sampling via venous catheters. Even though no factor is a major source of BG, it could at least partially influence BG assay performance. Thus, BG detection has a limited usefulness as a screening method for IFIs in patients with haematological malignancies.
Mycoses | 2012
Zdenek Racil; Jana Winterová; Michal Kouba; Pavel Zak; Ludmila Malásková; Lucie Burešová; Martina Tošková; Martina Lengerová; Iva Kocmanová; Barbora Weinbergerová; Shira Timilsina; Monika Rolencová; Petr Cetkovsky; Jiri Mayer
The objective of this retrospective study was to evaluate results from voriconazole therapeutic drug monitoring (TDM) in haematological patients in routine clinical practice. Between 2005 and 2010, 1228 blood samples were obtained from 264 haematological patients (median 3 samples/patient; range 1–27) receiving voriconazole for targeted/preemptive treatment of invasive aspergillosis (IA) (46.3% of samples), empirical therapy (12.9%) or prophylaxis (40.8%). A high‐pressure liquid chromatography assay was used to analyse voriconazole concentrations. Clinical and laboratory data were analysed retrospectively. The median of the detected voriconazole plasma concentration was 1.00 μg ml−1 (range <0.20–13.47 μg ml−1). Significant inter‐ and intra‐patients variability of measured concentrations (81.9% and 50.5%) were identified. With the exception of omeprazole administration, there was no relevant relationship between measured voriconazole concentrations and drug dose, route administration, age, gender, CYP2C19*2 genotype, gastrointestinal tract abnormality, administration via nasogastric tube, serum creatinine, and liver enzymes. However, per patient analysis identified significant role of individual voriconazole dose and drug form change on measured plasma concentration. Measured voriconazole concentrations did not correlate with the treatment outcome of patients with IA. We only identified a limited number of adverse events related to voriconazole therapy; however, the median plasma concentration was not different from concentrations measured in samples without reported toxicity. Our retrospective study has suggested that routine monitoring of voriconazole plasma concentrations has probably only a limited role in daily haematological practice.
Journal of Clinical Microbiology | 2010
Kristyna Hrncirova; Martina Lengerová; Iva Kocmanová; Zdenek Racil; Pavlína Volfová; Dita Paloušová; Mojmír Moulis; Barbora Weinbergerová; Jana Winterová; Martina Tošková; Šárka Pospíšilová; Jiri Mayer
ABSTRACT We present a method for rapid and simple detection of clinically relevant mucormycetes of the Mucorales order in cultures and clinical samples. This seminested real-time PCR uses mucormycete-specific primers and is followed by species identification using high-resolution melt (HRM) analysis. The method is highly suitable for routine clinical diagnostics.
Journal of Clinical Microbiology | 2014
Martina Lengerová; Zdenek Racil; Kristyna Hrncirova; Iva Kocmanová; Pavlína Volfová; Dita Ricna; Petr Bejdák; Mojmír Moulis; Zdenek Pavlovsky; Barbora Weinbergerová; Martina Tošková; Jiri Mayer
ABSTRACT Rapid differential diagnostics of pulmonary infiltrates suspected of invasive fungal disease in an immunocompromised host and early initiation of effective antifungal therapy are crucial for patient outcomes. There are no serological tests available to detect mucormycetes; therefore, PCR-based methods are highly suitable. We validated our previously published PCR followed by high-resolution melt analysis (PCR/HRMA) to detect Rhizopus spp., Rhizomucor pusillus, Lichtheimia corymbifera, and Mucor spp. in bronchoalveolar lavage (BAL) samples from immunocompromised patients who were at risk of invasive fungal disease. All PCR/HRMA-positive samples were retested using novel real-time quantitative PCR (RQ PCR) assays specific to the species identified. In total, between January 2009 and December 2012 we analyzed 99 BAL samples from 86 patients with pulmonary abnormalities using PCR/HRMA. Ninety (91%) BAL samples were negative, and 9 (9%) samples were positive. The sensitivity and specificity of PCR/HRMA were 100% and 93%, respectively. By combining the positive results of PCR/HRMA with positive RQ PCR results, the specificity was raised to 98%. PCR/HRMA, due to its high negative predictive value (99%), represents a fast and reliable tool for routine BAL sample screening for the differential diagnosis of pulmonary infiltrates in immunocompromised patients for the four most clinically important mucormycetes.
Mycoses | 2013
Zdenek Racil; Iva Kocmanová; Martina Tošková; Jana Winterová; Martina Lengerová; Shira Timilsina; Jiri Mayer
There are discrepancies in the retrospective studies published in literature of whether or not bacteraemia could lead to false positivity of 1,3‐β‐D (BG) glucan assay. We performed, for the first time, a prospective study evaluating the role of bacterial bloodstream infection to the reactivity of BG assay. Twenty‐six episodes of bacteraemia that occurred in high‐risk haematological patients were included in our study. Consecutive BG levels >80 pg ml−1 were required for test positivity. Only 2 of 26 patients were BG positive – both with IFDs. Thus, we prospectively did not prove bacteraemia as the source of cross reactivity of BG assay in haematological patients.
Leukemia & Lymphoma | 2013
Ivana Jeziskova; Filip Rázga; Martina Tošková; Dana Dvorakova; Shira Timilsina; Jiri Mayer; Zdenek Racil
Acquired mutations in the IDH1 and IDH2 genes have been detected in various hematological disorders, including acute myeloid leukemia (AML), where the incidence has been reported to be 15% [1 – 6]. Th e IDH1 and IDH2 genes encode enzymes that catalyze oxidative decarboxylation of isocitrate to α -ketoglutarate ( α -KG). Somatic mutations cause their dysfunction and an accumulation of aberrant 2-hydroxygluterate (2-HG) product in cells [5]. Th e decreased supply of α -KG or increased accumulation of 2-HG (i.e. metabolic biomarker of mutant IDH1/2 enzyme activity) is considered to be a possible basis for the oncogenic properties of IDH mutants [7]. Mutations in the IDH2 gene exclusively aff ect hotspot regions c.G419 (p.R140) and/or c.G515 (p.R172), which both localize in exon 4. Th e most frequent mutation in patients with AML reported to date is heterozygous c.G419A (p.R140Q) [8,9]. The use of IDH2 mutations for the monitoring of minimal residual disease (MRD) is under investigation and still remains unclear [8,10,11]. Recently, using conventional sequencing, we have reported that IDH2 mutations are stable and associated with the course of AML [11]. However, the sensitivity of direct sequencing limits its use for MRD monitoring. Thus, we developed a novel realtime quantitative polymerase chain reaction (RQ-PCR) assay that enables rapid and sensitive quantification of the IDH2 c.G419A (p.R140Q) mutation. Here, we report on the applicability of the newly developed method for MRD monitoring in patients with AML and then compare the results with those obtained from monitoring NPM1 mutations. We investigated 60 unique samples [43 bone marrow (BM) and 17 peripheral blood (PB), Figure 1(A)] at different time points of AML treatment of eight patients with AML harboring the IDH2 mutation c.G419A (p.R140Q) who were previously or currently being treated in our institution from 2008 to 2012. With the exception of a single patient (patient no. 7) who received palliative treatment using low-dose cytosine arabinoside, all patients received curative therapy, including standard induction (45 mg/m 2 daunorubicin for 3 days and 100 – 200 mg/m 2 cytosine arabinoside for 7 days) or a double induction with the same drug combination. Additional treatment consisted of two to three consolidation chemotherapies (mostly highdose 3 g/m 2 cytosine arabinoside BID on days 1, 3 and 5, or 100 – 200 mg/m 2 cytosine arabinoside for 5 days and 9 mg/m 2 mitoxantrone for 2 days). Four patients received hematopoietic stem cell transplant. Within this cohort, 6/8 patients harbored a parallel NPM1 mutation (fi ve patients had mutation A and one had mutation B). Th e patient characteristics are summarized in Figure 1(A). All patients signed an informed consent before the samples were collected, and the study was approved by the Institutional Review Board. PB (patient nos. 1, 4 and 7) and BM (patient nos. 2, 3, 5, 6 and 8) samples were collected in ethylenediaminetetraacetic acid (EDTA) in a total volume of 5 mL each. Samples were collected at the time of diagnosis, monthly during induction and consolidation, every 2 – 3 months during follow-up, and at the time of hematological relapse. Th e number of samples per patient ranged between three and 14 and the median follow-up was 13.0 months (range 4 – 25 months). Th e genomic DNA was extracted according to a previously published protocol [12]. Quantifi cation of the IDH2 c.G419A (p.R140Q) mutation was performed using DNA-based RQ-PCR with a specifi c set of primers and a locked nucleic acids (LNA) probe that was specifi c for the mutant allele. Th e sequences of the oligonucleotides and PCR protocol are shown in Figures 1(B) – 1(D). L eu k L ym ph om a D ow nl oa de d fr om in fo rm ah ea lth ca re .c om b y T he U ni ve rs ity o f M an ch es te r on 1 0/ 29 /1 4
Mycoses | 2013
Martina Tošková; Dita Paloušová; Iva Kocmanová; Zdenek Pavlovsky; Shira Timilsina; Martina Lengerová; Jiri Mayer; Zdenek Racil
Invasive mould diseases (IMD) are serious, life-threatening complications in immunocompromised hosts. Patients with acute myeloid leukaemia (AML) as well as those after allogeneic bone marrow transplantation represent the highest risk group, with an IMD incidence of approximately 10%. Invasive aspergillosis (IA) is the most frequent type and represents 96% of all IMD cases. The incidence of IA in this high-risk group of patients is 10% and the mortality is 30–40%.1 In more than 90% of IA cases, the lungs are affected or the disease is disseminated. Importantly, isolated gastrointestinal involvement is very uncommon.2 Molecular techniques have been used in the diagnosis and identification of mould diseases and new fungal species morphologically similar to Aspergillus fumigatus have been described. The Aspergillus section Fumigati now includes anamorphic Aspergillus species and teleomorphic Neosartorya species. Neosartorya spp. is a filamentous fungus that is commonly found in soil throughout the world. Invasive mould infections caused by Neosartorya spp. have very rarely been described in literature.
Molecular Diagnosis & Therapy | 2012
Filip Rázga; Tomáš Jurček; Daniela Zackova; Dana Dvorakova; Martina Tošková; Ivana Jeziskova; Jiri Mayer; Zdenek Racil
Background and ObjectiveThe availability of different tyrosine kinase inhibitors (TKIs) with distinct antileukemic potency enables optimization of current therapeutic regimens; however, some patients lose their therapy response and acquire TKI resistance. In this study, we describe a single-center experience of monitoring BCR-ABL1 kinase domain (KD) mutations and discuss the impact of treatment on mutation selection.MethodsChronic myelogenous leukemia (CML) patients treated with TKIs at the Department of Internal Medicine — Hematology and Oncology, Masaryk University and University Hospital Brno during 2003–2011 were included in this study. A total number of 100 patients who did not achieve an optimal therapy response or who lost their therapy response were screened for the presence of BCR-ABL1 KD mutations, using direct sequencing.ResultsOur data show that pretreatment with non-specific non-TKI drugs prior to TKI therapy does not preferentially select for initial BCR-ABL1 KD mutations, in contrast to first-line imatinib therapy, which shows a clear predominance of T315I or P-loop mutations compared with mutations located in other KD regions. In addition, the median time to detection of P-loop mutations was substantially shorter in patients treated with first-line imatinib than in those pretreated with non-TKI drugs. Furthermore, analysis of CML patients who had recurrent resistance to TKI therapy revealed possible therapy-driven selection of BCR-ABL1 KD mutations. Finally, we confirm the previously described poor prognosis of CML patients with mutations in the BCR-ABL1 KD, since 40.0% of our CML patients who harbored a BCR-ABL1 KD mutation died from CML while receiving TKI treatment. Moreover, among the patients who are still on treatment, 27.8% have already progressed. Our data also confirm the unique position of the T315I mutation with respect to its strong resistance to currently approved TKIs.ConclusionOn the basis of the ‘real-life’ data described in this study, it is possible that the therapy itself results in its failure and selects the most resistant mutations under the selective pressure of the applied therapy regimen in some CML patients who harbor BCR-ABL1 KD mutations.
Leukemia & Lymphoma | 2013
Zdenek Racil; Martina Tošková; Iva Kocmanová; Lucie Burešová; Michal Kouba; Lubos Drgona; Lucia Masárová; Tomáš Guman; Elena Tóthová; Julia Gabzdilova; Kristina Forsterova; Jan Haber; Barbora Ziakova; Eva Bojtárová; Monika Rolencová; Shira Timilsina; Petr Cetkovsky; Jiri Mayer
Abstract The objective of this retrospective, multicenter study was to evaluate the efficacy and safety of micafungin as empirical antifungal therapy during febrile neutropenia (FN) in 73 hematological patients from six centers in two countries. All patients received 100 mg of micafungin/day. The overall favorable response rate (RR) was 64.8% when the resolution of fever during neutropenia was included in the response criteria and 84.5% when excluded. A significantly lower favorable RR in patients with persistent fever and non-specific pulmonary infiltrates compared to patients with persistent fever only (82.8 vs. 52.4%, respectively; p = 0.011) was not found when resolution of fever was not included in the composite endpoint criteria (93.1 vs. 78.6%, respectively; p = 0.180). Breakthrough fungal disease developed in 2.7% of patients. Treatment was discontinued in 16.4% of cases. Only one patient (1.4%) discontinued therapy due to an adverse event. Posaconazole prophylaxis improved favorable RR when defervescence was included as composite endpoint criterion (p = 0.047), but not when it was excluded (p = 0.485). However, neutrophil recovery did not influence favorable RR (p = 0.803 and p = 0.112, respectively). These data suggest that micafungin is safe and effective as an empirical therapy in patients with FN.
European Journal of Clinical Microbiology & Infectious Diseases | 2010
Zdeněk Ráčil; Iva Kocmanová; Barbora Weinbergerová; Martina Tošková; Jana Winterová; Martina Lengerová; Lucie Burešová; Shira Timilsina; Jiří Mayer
We are reporting a study evaluating the crossover of antigens reacting in Platelia Aspergillus (PA) enzyme-linked immunosorbent assay (ELISA) from faeces to vessels during mucositis as a possible cause of false-positivity of this test. In our series of 102 episodes of different grades of mucositis, we found strong reactivity of faeces in the PA ELISA test irrespective of the grade of mucositis, the percentage of oral food intake or the presence of total parenteral nutrition. However, none of the patients included in the study were positive in the serum (when the criterion of two samples with cut-off index of positivity [IP] > 0.5 was used).