Risk factors for breakthrough invasive fungal infection during secondary prophylaxis

Cornely, Oliver A.; Böhme, Angelika; Reichert, Dietmar; Reuter, Stefan; Maschmeyer, Georg; Maertens, Johan; Buchheidt, Dieter; Paluszewska, Monika; Arenz, Dorothee; Bethe, Ullrich; Effelsberg, Jenny; Lövenich, Harry; Sieniawski, Michal; Haas, Antje; Einsele, Hermann; Eimermacher, Hartmut; Martino, Rodrigo; Silling, Gerda; Hahn, Moritz; Wacker, Sidonie; Ullmann, Andrew J.; Karthaus, Meinolf

doi:10.1093/jac/dkn027

Cited by 63 publications

(52 citation statements)

References 26 publications

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“…Two patients from the ITC group were excluded because of incomplete data (unknown formulation of ITC and missing leukocyte counts). Some data for 5 patients from the CAS group and 22 patients from the ITC group were part of an earlier publication on risk factors for breakthrough infections [9]. Owing to the sample size, no formal matching of patients was performed.…”

Section: Resultsmentioning

confidence: 99%

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Efficacy of caspofungin and itraconazole as secondary antifungal prophylaxis: analysis of data from a multinational case registry

Vehreschild

Sieniawski

Reuter

et al. 2009

International Journal of Antimicrobial Agents

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Section: Resultsmentioning

confidence: 99%

“…However, these patients are at high risk of recurrent IFD, often with fatal outcome. The reported incidence rates of recurrent IFD range from 16% to 33% [9][10][11], and IFD-related mortality may be as high as 88% [10,12,13].…”

Section: Introductionmentioning

confidence: 99%

Efficacy of caspofungin and itraconazole as secondary antifungal prophylaxis: analysis of data from a multinational case registry

Vehreschild

Sieniawski

Reuter

et al. 2009

International Journal of Antimicrobial Agents

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“…This is in line with earlier studies and reflects the importance of immune reconstitution in preventing the reactivation of IFI. 5,6,16,[22][23][24] The literature also found the following risk factors: hierarchy of diagnosis (proven and probable versus possible), conditioning regimen, duration of neutropenia, GVHD, organ dysfunction and progression of the underlying diseases. However, we failed to confirm the results of these studies.…”

Section: Discussionmentioning

confidence: 99%

Hematopoietic SCT in patients with a history of invasive fungal infection

Zhang

Song

Wang

et al. 2008

Bone Marrow Transplant

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Earlier invasive fungal infections (IFI) put recipients of hematopoietic SCT (HSCT) at a high risk of IFI-related mortality. We retrospectively assessed the feasibility of HSCT for patients with a history of IFI and the efficacy of secondary prophylaxis. From January 2001 to December 2007, 49 patients with a history of IFI underwent HSCT and most of them received broadspectrum antifungal agents as secondary prophylaxis. After a median follow-up of 355 days (15-967), nine patients experienced failure of IFI prophylaxis, including three cases of IFI-related death, leading to a 2-year cumulative incidence of 18.4 and 6.1%, respectively. Four risk factors for the failure of prophylaxis were found, namely time interval from the diagnosis of IFI to transplantation, residual diseases before transplantation, infection with CMV and use of corticosteroid for the treatment of GVHD. A similar outcome can be achieved in recipients of Auto-and Auto-HSCT. Despite a higher risk of post-transplant progression, residual features of IFI did not affect the overall outcome of HSCT. In conclusion, a history of IFI and residual features are not contraindications to HSCT and secondary prophylaxis by broad-spectrum antifungal agents can protect patients from relapse or progression of an earlier infection.

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“…The clinical efficacy of voriconazole against the majority of fungal pathogens [Chabrol et al 2010;Gergis et al 2010;Martin et al 2010;Torres et al 2010;Trifilio et al 2007] makes it potentially very useful for the prevention of IFIs in patients with hematologic malignancies. However, given that, at present, voriconazole is widely recommended as first-line treatment for proven or probable IA [Cordonnier et al 2010;Cornely et al 2008;El-Cheikh et al 2010], this may result in strategic and therapeutic dilemmas if used as prophylaxis and in an increased risk of selection of resistant species.…”

Section: The Rationale For Voriconale As Antifungal Prophylaxismentioning

confidence: 99%

“…There is the possibility of serious adverse events, such as prolonged visual disturbances, QT-interval prolongation and hepatic toxicity, therefore close monitoring of cardiac, visual, and liver function is strongly recommended [Ananda-Rajah et al 2008;Chang et al 2008;Cornely et al 2008;Vande Broek and Schots, 2009]. In addition, there have been a small number of reports of squamous cell carcinoma as well as melanoma during long-term voriconazole treatment [Bruggemann et al 2009;Pascual et al 2008;Rogers et al 2011], potentially associated with the photosensitivity effect of this agent.…”

Section: Monitoring Voriconazole Plasma Levelsmentioning

confidence: 99%

Voriconazole and its clinical potential in the prophylaxis of systemic fungal infection in patients with hematologic malignancies: a perspective review

Zabalza

Gorosquieta

Equiza

et al. 2013

Therapeutic Advances in Hematology

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Invasive fungal infections (IFIs) have become high prevalence in patients with hematologic malignancies. Drug-based strategies for IFIs include various approaches such as prophylactic, empiric, preemptive, and directed treatment. Prophylaxis is an attractive strategy in high-risk patients, given the lack of reliable diagnostics and the high mortality rate associated with IFIs. Prophylaxis includes the use of antifungal drugs in all patients at risk. An ideal antifungal compound for prophylaxis should have a potent and broad activity, be available both orally and intravenously, and have a low toxicity profile. Voriconazole fulfills all these criteria. The clinical efficacy of voriconazole against the majority of fungal pathogens makes it potentially very useful for the prevention of IFIs in patients with hematologic malignancies. Voriconazole appears to be very effective for the primary and secondary prevention of IFIs in these patients and recipients of allogeneic hematopoietic stem-cell transplantation. Randomized controlled trials evaluating voriconazole as primary antifungal prophylaxis in patients with neutropenia treated for a variety of hematologic malignancies have been performed, confirming its value as a prophylactic agent. Voriconazole is generally safe and well tolerated; however, its use is also associated with a number of concerns. In most patients with hematologic malignancies there is the potential for pharmacokinetic drug-drug interactions given that voriconazole is metabolized through the P450 cytochrome system.

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Risk factors for breakthrough invasive fungal infection during secondary prophylaxis

Abstract: Duration of neutropenia, high-dose cytarabine, prior antibiotic therapy and a partial response to the first IFI therapy were risk factors for recurrent IFI and should be considered in AML patients with prior pulmonary IFI undergoing further chemotherapy.

Cited by 63 publications

References 26 publications

Efficacy of caspofungin and itraconazole as secondary antifungal prophylaxis: analysis of data from a multinational case registry

Efficacy of caspofungin and itraconazole as secondary antifungal prophylaxis: analysis of data from a multinational case registry

Hematopoietic SCT in patients with a history of invasive fungal infection

Voriconazole and its clinical potential in the prophylaxis of systemic fungal infection in patients with hematologic malignancies: a perspective review

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