University of Wuerzburg Medical Center

Würzburg, Germany

University of Wuerzburg Medical Center

Würzburg, Germany
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Lee M.,TU Munich | Eyer F.,TU Munich | Felgenhauer N.,TU Munich | Klinker H.H.F.,University Of Wuerzburg Medical Center | Spinner C.D.,TU Munich
AIDS Research and Therapy | Year: 2015

A 21 year old MSM patient with newly diagnosed HIV infection was hospitalized in our department after ingestion of an overdose of his antiretroviral therapy (ART) comprising dolutegravir (DTG - Tivicay®) and tenofovir disaproxil fumarate/emtricitabine (Truvada®) in suicidal intention. On admission, the patient did not show any clinical signs of intoxication and laboratory findings were unremarkable. After 6 hours of intensive care monitoring, the patient was referred to a psychiatric clinic. 5 days after the day of intoxication, serum creatinine levels increased to high normal values (1.2 mg/dl). However, levels never exceeded the upper threshold. 8 and 12 weeks later, serum creatinine normalized to levels measured prior to the intoxication. No other adverse events occurred, and the patient does not suffer from permanent impairments. © 2015 Lee et al.; licensee BioMed Central.


Niewoehner D.,Minneapolis VA Health Care System | Niewoehner D.,University of Minnesota | Collins G.,University of Minnesota | Nixon D.,Virginia Commonwealth University | And 6 more authors.
HIV Medicine | Year: 2015

Objectives: The aim of the study was to describe the prevalence and correlates of chronic obstructive pulmonary disease (COPD) in a multicentre international cohort of persons living with HIV (PLWH). Methods: We performed a cross-sectional analysis of adult PLWH, naïve to HIV treatment, with baseline CD4 cell count >500 cells/μL enrolled in the Pulmonary Substudy of the Strategic Timing of AntiRetroviral Treatment (START) trial. We collected standardized, quality-controlled spirometry. COPD was defined as forced expiratory volume in 1s:forced vital capacity (FEV1:FVC) ratio less than the lower limit of normal. Results: Among 1026 participants from 80 sites and 20 countries, the median age was 36 [interquartile range (IQR) 30, 44] years, 29% were female, and the median time since HIV diagnosis was 1.2 (IQR 0.4, 3.5) years. Baseline median CD4 cell count was 648 (IQR 583, 767) cells/μL, median viral load was 4.2 (IQR 3.5, 4.7) log10 HIV-1 RNA copies/mL, and 10% had a viral load ≤400 copies/mL despite lack of HIV treatment. Current/former/never smokers comprised 28%/11%/61% of the cohort, respectively. COPD was present in 6.8% of participants, and varied by age, smoking status and region. Forty-eight per cent of those with COPD reported lifelong nonsmoking. In multivariable regression, age and pack-years of smoking had the strongest associations with FEV1:FVC ratio (P<0.0001). There was a significant effect of region on FEV1:FVC ratio (P=0.010). Conclusions: Our data suggest that, among PLWH who were naïve to HIV treatment and had CD4 cell counts >500 cells/μL, smoking and age were important factors related to COPD. Smoking cessation should remain a high global priority for clinical care and research in PLWH. © 2015 British HIV Association.


Heinz W.J.,University of Wuerzburg Medical Center | Einsele H.,University of Wuerzburg Medical Center | Helle-Beyersdorf A.,University of Wuerzburg Medical Center | Zirkel J.,University of Wuerzburg Medical Center | And 4 more authors.
Transplant Infectious Disease | Year: 2013

Introduction: Posaconazole is recommended for prophylaxis of fungal infections and for salvage therapy of invasive aspergillosis after stem cell transplantation. An impact of drug concentration on efficacy has been suggested. Methods: In this study, we investigated serum levels of posaconazole in 262 samples from 64 allogeneic stem cell recipients. Results: A high degree of interindividual variation was observed. Concentrations were significantly higher for male patients compared with female patients (median 570 and 426 ng/mL, respectively), but no differences for age or dosing groups (400 mg twice daily [BID] or 200 mg three times a day) could be detected. The predictive value of the first determined posaconazole concentration in steady state and of a concentration >500 and 700 ng/mL at any time was evaluated, compared with patients with a first level <300 ng/mL (mean 10.3%, median 0%). Conclusion: In patients receiving 400 mg BID, the mean rate of serum levels >500 ng/mL in subsequent determinations was higher, if the first serum concentration during steady state was >300 ng/mL (mean 61.1%, median 60%, P = 0.002) or >500 ng/mL (67.7%, median 75%, P = 0.002). Based on this retrospective analysis, a posaconazole serum concentration >500 ng/mL at any time point might also help to predict sufficient drug concentrations. © 2013 John Wiley & Sons A/S.


Heinz W.J.,University of Wuerzburg Medical Center | Silling G.,University of Munster | Bohme A.,Onkologikum
Current Medical Research and Opinion | Year: 2011

Objective: Invasive fungal infections (IFIs) are an important cause of morbidity and mortality, particularly in patients with cancer. The triazole voriconazole, given as oral or intravenous formulation, has a high bioavailability and proven efficacy against invasive aspergillosis, candidiasis and other fungi. We aimed to assess the utilisation, efficacy and safety of voriconazole with emphasis on the route of administration under standard clinical conditions. Methods: Prospective, observational study performed by 17 hospitals and office-based physicians in Germany. Results: A total of 264 patients received oral (53) or intravenous (22) voriconazole or both formulations sequentially (25). Of 228 patients with specified fungal diagnosis, 95 (36.0) had aspergillosis, 73 (27.7) candidiasis. Sixty (22.7) received voriconazole for other fungal indications (OFI). In 195 of 226 patients (86.2), treatment was successful (39.8 cured and 46.5 partial response). In terms of primary diagnoses, favourable responses were noted in 90 for pulmonary aspergillosis, 85 for candidiasis and 87 for OFI. Microbiological success was documented in 138 patients, of whom 105 (76.1) had complete eradication of fungi. Response rates by initial route were similar for oral and intravenous administration (86 and 87). Twenty-six of 264 patients died during the study, 53 patients experienced a serious adverse event (five treatment related), and 10 withdrew due to all-causality adverse events (AEs). Tolerability was assessed as very good in 55, and good in 40 of patients. Conclusions: Voriconazole as oral or intravenous formulation was well tolerated and equally effective in critically ill patients with IFIs. This study in daily care confirms the outcomes of controlled clinical trials. © 2011 Informa UK Ltd All rights reserved.


Heinz W.J.,University of Wuerzburg Medical Center | Egerer G.,University of Heidelberg | Lellek H.,University of Hamburg | Boehme A.,Onkologikum Frankfurt am Museumsufer | Greiner J.,University of Ulm
Mycoses | Year: 2013

Invasive aspergillosis is an important cause of morbidity and mortality in haematological patients. Current guidelines recommend voriconazole as first-line therapy. A change in class of antifungal agent is generally recommended for salvage therapy. The focus of this analysis was to assess if posaconazole is suitable for salvage therapy following voriconazole treatment. This was a retrospective investigation on patients with sequential antifungal therapy of posaconazole after voriconazole identified at four German hospitals. Response rates at 30 and 60days following start of posaconazole application and toxicity of azoles by comparing liver enzymes and cholestasis parameters were evaluated. Data were analysed by descriptive statistics. Overall, the success rate was 72.2% [15 of 36 patients showed complete response (41.7%), 11 patients partial response (30.6%) at any time point], eight patients failed treatment and two were not evaluable. Mean laboratory values increased during voriconazole and decreased during posaconazole treatment: aspartate aminotransferase (increase: 31.9Ul-1 vs. decrease: 19.6Ul-1), alanine aminotransferase (32.4Ul-1 vs. 19.8Ul-1), gamma-glutamyl transferase (124.2Ul-1 vs. 152.3Ul-1) and alkaline phosphatase (71.5Ul-1 vs. 40.3Ul-1) respectively. No patient discontinued posaconazole therapy due to an adverse event. In this analysis posaconazole was a safe and effective antifungal salvage therapy in patients with prior administration of another triazole. © 2012 Blackwell Verlag GmbH.


Spinner C.D.,Ludwig Maximilians University of Munich | Wille F.,TU Munich | Schwerdtfeger C.,Ludwig Maximilians University of Munich | Thies P.,Ludwig Maximilians University of Munich | And 5 more authors.
AIDS Research and Therapy | Year: 2015

Background: While HIV, AIDS and atypical Mycobacterium infections are closely linked, the use of Integrase-Inhibitor based cART, notably raltegravir-based regimens is more widespread. RAL should be double-dosed to 800mg semi-daily in situation of rifampicin co-medication, because RAL is more rapidly metabolized due to rifampicin-induced Uridine-5'-diphosph- gluronosyl-transferase (UGT1A1). Recently, it was speculated that chewed RAL might lead to increased absorption, which might compensate the inductive effect of rifampicin-rapid metabolized RAL, as part of cost-saving effects in countries with high-tuberculosis prevalence and less economic power. Methods: We report measurement of raltegravir pharmacokinetics in a 34-year AIDS-patient suffering from disseminated Mycobacterium avium infection with necessity of parenteral rifampicin treatment. RAL levels were measured with HPLC (internal standard: carbamazepine, LLQ 11ng/ml, validation with Valistat 2.0 program (Arvecon, Germany)). For statistical analysis, a two-sided Wilcoxon signed rank test for paired samples was used. Results: High intra-personal variability in raltegravir serum levels was seen. Comparable Cmax concentrations were found for 800mg chewed and swallowed RAL, as well as for 400mg chewed and swallowed RAL. While Cmax seems to be more dependent from overall RAL dosing than from swallowed or chewed tablets, increased AUC12 is clearly linked to higher RAL dosages per administration. Anyway, chewed raltegravir showed a rapid decrease in serum levels. Conclusions: We found no evidence that chewed 400mg semi-daily raltegravir in rifampicin co-medication leads to optimized pharmacokinetics. There is need for more data from randomized trials for further recommendations. © Spinner et al.; licensee BioMed Central.


Heinz W.J.,University of Wuerzburg Medical Center | Zirkel J.,University of Wuerzburg Medical Center | Kuhn A.,University of Wuerzburg Medical Center | Schirmer D.,University of Wuerzburg Medical Center | And 3 more authors.
Antimicrobial Agents and Chemotherapy | Year: 2011

For posaconazole, drug monitoring is suggested, but the relevance of timing for the determination of posaconazole concentration (PC) remains unclear. We investigated the variation of PC before and 4 and 8 h after the administration of 400 mg of posaconazole. Mean concentrations were 645, 678, and 616 ng/ml. The differences between trough and maximum concentrations were below 20% in 17 and below 30% in 20 of 25 patients. Hence, untimed posaconazole plasma concentrations give reliable information for most patients. Copyright © 2011, American Society for Microbiology. All Rights Reserved.


Springer J.,University of Wuerzburg Medical Center | Springer J.,Public Health Wales Microbiology | Morton O.,St James's Hospital | Morton O.,University of Western Sydney | And 10 more authors.
Journal of Clinical Microbiology | Year: 2013

Samples from patients at high risk for invasive aspergillosis (IA) were prospectively collected and analyzed for the presence of molecular markers of fungal infection. Serum specimens were screened for galactomannan and Aspergillus DNA, and wholeblood specimens were screened only for Aspergillus DNA. Fungal infections were categorized according to the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group, National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) criteria. Forty-seven cases (proven and probable IA) and 31 controls (no evidence of IA) were selected retrospectively for this case-control study, comprising 803 samples, in order to determine the performance of whole-blood PCR, serum PCR, and serum galactomannan testing. Although no single assay was able to detect every case of IA, a combination of different assays provided the best performance. There was no significant difference between the use of whole-blood and serum specimens for PCR-based diagnosis of IA, but there was a trend for whole blood to be more sensitive (85% versus 79%) and to yield an earlier positive result (36 days versus 15 days) than for serum. However, DNA extraction from serum specimens is easier and faster than that from whole-blood specimens, and it allows the same specimen to be used for both galactomannan and PCR assays. In conclusion, the appropriate sample type for DNA extraction should be determined by the local requirements and the technical platforms available at each individual center. A combination of biomarker tests offered the best diagnostic utility for detecting IA. Copyright © 2013, American Society for Microbiology.


Rogers T.R.,St James's Hospital | Morton C.O.,St James's Hospital | Morton C.O.,University of Western Sydney | Springer J.,University of Wuerzburg Medical Center | And 6 more authors.
British Journal of Haematology | Year: 2013

Invasive aspergillosis (IA) is a leading complication of intensive treatment for haematological malignancies. Earlier diagnosis should facilitate effective antifungal therapy and prevent progression to invasive disease, which is often lethal. Polymerase chain reaction (PCR) assays, targeting the 28S and ITS ribosomal gene regions respectively, were evaluated for early detection of Aspergillus DNA and for diagnostic utility in patients receiving treatment in two busy haematopoietic stem cell transplant centres. Patients undergoing intensive chemotherapy, autologous or allogeneic transplant were eligible for inclusion in the study. EDTA blood and serum samples for circulating Aspergillus biomarkers, including galactomannan (GM), were collected twice-weekly on a prospective basis from all study patients who were categorized according to international consensus criteria for defining invasive fungal disease (IFD). Of 278 patients recruited there were 44 probable IA cases and only one proven case. Moderate sensitivity and specificity, poor positive predictive value (50-80%), but good negative predictive value (>80-90%) were common to both PCR assays. Overall biomarker performance could be improved by combining positive results of either PCR assay with GM taken within a 12-d period. The addition of PCR to GM monitoring in high-risk patients with haematological malignancies provides greater diagnostic accuracy in invasive aspergillosis. © 2013 John Wiley & Sons Ltd.


PubMed | TU Munich and University Of Wuerzburg Medical Center
Type: | Journal: AIDS research and therapy | Year: 2015

A 21year old MSM patient with newly diagnosed HIV infection was hospitalized in our department after ingestion of an overdose of his antiretroviral therapy (ART) comprising dolutegravir (DTG - Tivicay) and tenofovir disaproxil fumarate/emtricitabine (Truvada) in suicidal intention. On admission, the patient did not show any clinical signs of intoxication and laboratory findings were unremarkable. After 6hours of intensive care monitoring, the patient was referred to a psychiatric clinic. 5days after the day of intoxication, serum creatinine levels increased to high normal values (1.2mg/dl). However, levels never exceeded the upper threshold. 8 and 12weeks later, serum creatinine normalized to levels measured prior to the intoxication. No other adverse events occurred, and the patient does not suffer from permanent impairments.

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