Oliver A Cornely

..Patients with neutropenia resulting from chemotherapy for acute myelogenous leukemia or the myelodysplastic syndrome are at high risk for difficult-to-treat and often fatal invasive fungal infections...

..7% and 80%, respectively. No significant difference in toxicity was observed. Once-daily ceftriaxone plus tobramycin was not inferior to cefotaxime t.i.d. plus tobramycin qd in the empirical treatment of neutropenic fever...

..Whether reactivation of herpes simplex and varizella zoster can be influenced prophylactically has not been studied in randomised trials. In case of fever and detection of cytomegalovirus reactivation preemptive therapy should be given...

..In addition to re-examining the landmark clinical trials of the past, the more recent findings are put into perspective. The past year has been particularly rich in clinical trials...

..A larger phase III trial is warranted to further evaluate the lack of inferiority of the oral monotherapy regimen versus standard intravenous therapy...

..The objective of this review accumulating information on about 10.000 patients is to assess evidence based criteria primarily regarding the efficacy of antifungal prophylaxis in neutropenic cancer patients...

..Liposomal amphotericin B achieves maximum plasma levels at a dosage of 10 mg/kg per day, but clinical efficacy data for higher doses are lacking...

..N. vasinfecta, a plant pathogen, was identified by culture and genetic sequencing. Susceptibility testing revealed in vitro resistance for common antifungals...

..5% vs 17%), while nausea/vomiting was less (12.1% vs 5%). Once-daily ceftriaxone plus gentamicin was not inferior to cefepime t.i.d. plus gentamicin q.d. in the empirical treatment of neutropenic fever...

..Nystatin can be used topically whenever topical amphotericin B is not well tolerated. All currently available prophylactic antimycotics bear the risk of either unsatisfactory effectiveness or severe toxicity...

..Future investigations might aim at identifying drug level thresholds that allow for minimum toxicity and optimum efficacy of antifungal prophylaxis...

..In vitro data showed that intracellular uptake of micafungin by PBMCs depends on the albumin concentration of the surrounding medium, but only at non-physiological protein concentrations...

..Despite antifungal prophylaxis, risk of breakthrough IFD was high in both groups...

..We conducted a trial to analyze the efficacy and safety of voriconazole in the prevention of lung infiltrates during induction chemotherapy for acute myelogenous leukaemia (AML)...

..Data from this survey demonstrate the difficulty of putting drugs to their approved use in IFI...

..This study determines risk factors for recurrent IFI in leukaemia patients...

..The objective of this review of 50 studies accumulating more than 9000 patients is to assess evidence-based criteria with regard to the efficacy of antifungal prophylaxis in neutropenic cancer patients...

..Fluconazole 400 mg/d is recommended in allogeneic stem cell recipients until development of graft versus host disease only (Level A I). Aerosolized liposomal amphotericin B is recommended during prolonged neutropenia (Level B II)...

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..A change in dosing regimen on day 9 did not lead to higher exposures in these "poor absorbers" on day 15. Poor absorption may be enhanced with a high-fat meal, a nutritional supplement, or acidification...

..There is an ongoing discussion on whether these studies may be applied to transplant patients as well...

..Posaconazole reaches high concentrations within human PBMCs and PMNs and is, to a lesser extent, present in RBCs. The high intracellular concentrations might contribute to posaconazole efficacy and distribution...

..8%. The method was established as standard practice for the quantitation of intracellular antifungal concentrations and optimizes TDM by applying a rapid single method for 6 antifungals...

..may be switched to fluconazole. Caspofungin or micafungin might be preferred to anidulafungin in the neutropenic patient. L-AmB is a valuable second line treatment option for both groups of patients...

..As possible invasive mould disease probably reflects an early-stage of disease, a better outcome might be expected when treatment with liposomal amphotericin B is started preemptively...

..Future investigations may elucidate how anidulafungin performs clinically in comparison with the other echinocandins...

..Moxifloxacin prevented bacteraemia and shortened febrile episodes in patients receiving autologous PBSCT. No significant increase of adverse events in the moxifloxacin arm was observed, possibly due to the rather small sample size...

..Further prospective trials are recommended to evaluate comparative outcomes with a primary focus on patients with malignancies and invasive candidiasis...

..Early diagnosis of IFIs is imperative to facilitate treatment success. In all patients at risk for IFIs, blood cultures, galactomannan antigen and diagnostic imaging should be rigorously enforced...

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..Furthermore, for the first time, voriconazole levels in an intracerebral abscess were measured in this patient undergoing voriconazole oral therapy...

..01). CONCLUSIONS: Nosocomial BSI in neutropenic patients is significantly associated with an excess length of hospital stay, extra costs, and excess mortality. Severe sepsis and septic shock are closely correlated with an adverse outcome...

..More controlled and sufficiently scaled trials are imperative in order to establish micafungin as a reliable and safe option in clinical practice...

..In vitro data showed that intracellular uptake of anidulafungin by PBMCs depends on the albumin concentration of the surrounding medium, but only at low, i.e. non-physiological, protein concentrations...

..Symptoms rapidly resolved under posaconazole 200 mg q.i.d. treatment and the patient was able to undergo allogeneic haematopoietic stem cell transplantation on secondary prophylaxis with posaconazole...

..In this review article, we provide an overview of common infectious events associated with alemtuzumab therapy in CLL. We also discuss recommendations for effectively monitoring and managing infections in CLL patients...

..Reports of combination therapy or highly effective antifungal treatment (HEAT) in limited patient numbers are promising. New trials of combination therapy are warranted...

..In order to reduce the considerable mortality associated with SAB and to improve short- and long-term outcome, efforts should be made to increase adherence to recommendations...

..This case report describes the successful treatment of CDC during neutropenia using combination antifungal therapy and suggests controlled studies to establish optimal therapeutic strategies...

..We conclude from this large cohort of patients that voriconazole treatment together with neurosurgical management, whenever feasible, is currently the best approach to treat patients with CNS aspergillosis...

..Finally, the reader is provided with a brief overview on promising clinical trial designs and antifungals that might shape the treatment of invasive candidiasis in the years to come...

..To define better the safety profile of micafungin, an analysis of micafungin clinical trial safety data was undertaken...

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..Caspofungin has demonstrated efficacy in invasive candidiasis. However, in a comparative study, most patients (>83%) had candidaemia. Therefore, we performed a study in patients with non-fungaemic invasive candidiasis...

..In the future, the rate of catheter-related infections in neutropenic patients may be reduced by the use of catheters coated with antimicrobial agents...

..Oral bioavailability was especially low in patients with cytostatic therapy and/or bone marrow transplantation. Further studies are needed to establish the therapeutic range of the posaconazole concentrations...

..Corresponding adjustments of the starting dose according to the presence of diarrhea and according to age appear to be justified before TDM results are available...

..To investigate the economic impact of micafungin (MICA) for treatment of invasive candidiasis and candidaemia (systemic Candida infections), a health economic analysis was conducted comparing MICA with liposomal amphotericin B (L-AMB)...

..The combination therapy described here represents a novel approach to the treatment of Fusarium spp. in the immunocompromised host in whom Fusarium spp. are known to cause disseminated infection with high mortality...

..However, the value of prophylaxis has been questioned in centres with a low incidence of invasive fungal diseases (IFDs) and pre-emptive treatment strategies...

..Invasive zygomycosis accounts for a significant proportion of all invasive fungal diseases (IFD), but clinical data on the clinical course and treatment response are limited...

..This treatment strategy may represent an option for patients with poor immunologic responses to antiretroviral therapy despite undetectable viremia...

..If impaired kidney function is overt or expected on the grounds of, for example, uncontrolled diabetes, primary treatment of zygomycosis with posaconazole is an option...

..This case report describes a novel form of aspergillosis and underlines the need for an aggressive diagnostic approach in severely immunocompromised patients...

..Knowledge of the pathogenesis of IFIs and the activity, efficacy, and limitations of available treatment options will allow the selection of an appropriate antifungal agent for individual patients...

..An important aspect of this network is a qualified advanced training for physicians deployed at the CHIR-Net as part of a job rotation...

..Various conditions can cause a myocardial infarction in leukemias. We discuss the clinical management and the possible reasons for a subtotal thrombotic occlusion of the coronary artery...

..Recent developments in the epidemiology, diagnostics and treatment of fungal infections are reviewed and discussed in the context of the current state of art for the management of invasive fungal infections in cancer patients...

..In patients at high risk for IA, positive results for Aspergillus by PCR of blood samples are highly suggestive for IA and contribute to the diagnosis...

..CONCLUSIONS: Caspofungin is as effective as and generally better tolerated than liposomal amphotericin B when given as empirical antifungal therapy in patients with persistent fever and neutropenia...

..This review highlights recent developments in the epidemiology, diagnosis, and treatment in the context of state-of-the-art management of invasive fungal infections in cancer patients...

..One patient (0.4%) died from infection. Empirical first-line therapy with MPM as well as with P/T is safe and effective in febrile episodes emerging after ASCT. Higher response rates to primary treatment can be achieved with MPM...

..Invasive candidosis is increasingly prevalent in seriously ill patients. Our aim was to compare micafungin with liposomal amphotericin B for the treatment of adult patients with candidaemia or invasive candidosis...

..The data presented in this scenario show that use of caspofungin in hematology-oncology departments in Germany results in shorter hospital stays and is at least cost-neutral compared to use of L-AmB...

..The purpose of this article is to review recent studies in patient populations at high risk for invasive fungal infections...

..Currently recruiting multicentre trials on primary prophylaxis of IFI will have to show the preventive effectiveness of antifungals with mould activity and the incidence of zygomycosis under prospectively controlled conditions...

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..Voriconazole prophylaxis may be suitable for prevention of IA as well; however, the results of large clinical trials are still awaited...

..To assess the costs and cost-effectiveness of voriconazole in comparison to conventional amphotericin B (CAB) for the treatment of invasive aspergillosis in Germany...

..Antifungal therapy is often required for long periods. Safety data from the clinical development program of the triazole antifungal agent, posaconazole, were analyzed...

..This review highlights the new treatment options for the salvage setting in the context of the state-of-the-art management of IFI in cancer patients...

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..The response rate is significantly lower in documented infections than in fever of unknown origin (FUO). Evidence-based recommendations for diagnosis and treatment procedures are presented, reflecting study results and expert opinions...

..Immunocompromised hosts with cancer will benefit from consistent immunization practices. Further clinical trials are urgently warranted...

..In particular, leukopenia, female gender, prolonged duration of cannulation, antibiotics, and choice of insertion site could not be shown to be risk factors...

..With the advent of new antifungals the efficacy and safety of antifungal treatment have been improved substantially. This review summarises the new treatment options in candidaemia...