Aerosolized Liposomal Amphotericin B for the Prevention of Invasive Pulmonary Aspergillosis during Prolonged Neutropenia: A Randomized, Placebo‐Controlled Trial

Rijnders, Bart J. A.; Cornelissen, Jan J.; Slobbe, Lennert; Becker, Martin; Doorduijn, Jeanette K.; Hop, Wim C. J.; Ruijgrok, Elisabeth J.; Lüwenberg, Bob; Vulto, Arnold G.; Lugtenburg, Pieternella J.; Marie, S. de

doi:10.1086/586739

Cited by 254 publications

(194 citation statements)

References 19 publications

Supporting

Mentioning

184

Contrasting

Unclassified

Order By: Relevance

“…In a more recent randomized controlled trial, 25 mg once daily of liposomal amphotericin B administered for 2 days weekly until neutrophil recovery was randomly compared with placebo in 271 patients during 407 episodes of prolonged neutropenia. 10 Invasive pulmonary aspergillosis was diagnosed more frequently in the placebo arm (P ¼ 0.005 at the intent-to-treat analysis, OR 0.26).…”

Section: Discussionmentioning

confidence: 98%

“…Recent studies suggest that aerosolized lipidic formulations of amphotericin B could be effective in preventing airways IFIs in lung 7 and HSCT 8,9 and during prolonged neutropenia. 10 In lung transplant recipient, 50 mg of lipid complex amphotericin B was compared with 25 mg once daily of deoxycholate-amphotericin B inhalations: 7 in each arm full-dose treatment was delivered for 1 week followed by one inhalation weekly for 7 weeks. Both arms appeared to be associated with a low prevalence of fungal pneumonia in the early post transplant phase, but lipid complex formulation was associated with less adverse events.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Addition of aerosolized deoxycholate amphotericin B to systemic prophylaxis to prevent airways invasive fungal infections in allogeneic hematopoietic SCT: a single-center retrospective study

Morello

Pagani

Cóser

et al. 2010

Bone Marrow Transplant

View full text Add to dashboard Cite

Invasive fungal infections (IFIs) still pose major challenges in allogeneic hematopoietic SCT (HSCT), and effective antifungal prophylaxis remains a matter of debate. The aim of this retrospective study was to evaluate the toxicity and the impact of aerosolized deoxycholate amphotericin B (aero-d-AmB) on respiratory tract IFIs (airways IFIs) in a homogeneous cohort of allogeneic HSCT patients, transplanted at one institution. Since 1999, 102 consecutive patients were transplanted from matched related (N ¼ 71) or unrelated donor (MUD). Aero-d-AmB was administered for a median time of 16 days (range 2-45), in addition to systemic antifungal prophylaxis. Prolonged administration was neither associated with increased severe bacterial infections, nor with severe adverse events. In 16 patients in whom aero-d-AmB was delivered for less than 8 days, due to worsened clinical conditions or poor compliance, proven or probable airways IFIs were diagnosed in three cases (one mucormycosis and one fusariosis and one probable aspergillosis), whereas in 84 patients receiving aero-d-AmB for X8 days, one possible and one probable aspergillosis were diagnosed. A shortened administration (o8 days) of aero-d-AmB was therefore associated with an increased risk of both total airways IFIs (P ¼ 0.027) and proven/probable IFIs (P ¼ 0.012). At multivariate analysis prolonged aero-dAmB administration retained an independent protective effect on airways IFIs (P ¼ 0.026) whereas a MUD transplant was associated with a borderline increase of IFIs risk (P ¼ 0.052). Overall, 95.1% of patients did not experience airways IFIs and no patient died due to IFIs. In this cohort of patients, prolonged aero-d-AmB seems to have a role in preventing respiratory tract IFIs, but a randomized controlled trial is recommended to verify the impact of this prophylaxis in the setting of allogeneic HSCT.

show abstract

Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Addition of aerosolized deoxycholate amphotericin B to systemic prophylaxis to prevent airways invasive fungal infections in allogeneic hematopoietic SCT: a single-center retrospective study

Morello

Pagani

Cóser

et al. 2010

Bone Marrow Transplant

View full text Add to dashboard Cite

show abstract

“…All patients received fluconazole at an undisclosed dose and route. 67 Aerosolized liposomal amphotericin B appears to be effective, but does not prevent invasive fungal infections other than pulmonary (Level B II). Adverse events in these trials included coughing, bad taste and nausea.…”

Section: Polyenesmentioning

confidence: 99%

“…Adverse events in these trials included coughing, bad taste and nausea. [65][66][67] Polyenes have been applied intranasally, but there has never been any supporting randomized trial. Table S5) has been evaluated in different dosages ranging from 0.1 mg/kg/d to 1.0 mg/kg/tiw.…”

mentioning

confidence: 99%

Primary prophylaxis of invasive fungal infections in patients with hematologic malignancies. Recommendations of the Infectious Diseases Working Party of the German Society for Haematology and Oncology

Cornely¹,

Böhme²,

Buchheidt³

et al. 2009

Haematologica

156

102

View full text Add to dashboard Cite

© F e r r a t a S t o r t i F o u n d a t i o nO IntroductionThe rising incidence of invasive fungal infections, especially invasive aspergillosis, compromises therapeutic outcomes in hematologic cancer patients and in transplant recipients. [1][2][3][4][5] The utilization of newly introduced antifungal agents clearly improved the tolerability of patients combating severe underlying diseases. 6,7 Despite better outcome in primary treatment of invasive aspergillosis in comparison to conventional amphotericin B, response and survival require further improvement. 8,9 Additionally, early diagnosis of invasive fungal infections is critical.10 But usually diagnosis is delayed and thus hampers further treatment outcome. 11Therefore, the prevention of invasive fungal infections upfront has become the major goal in patient care in high-risk patient populations. Since the first edition of these recommendations regarding antifungal prophylaxis, close to 20 relevant publications have been added to the field, necessitating an updated review of their impact on clinical decision making. 12 On the other hand new meta-analyses on prophylaxis of invasive fungal infections have also been published, but do not differentiate between specific patient populations and risk factors. 13,14 To maintain comparability with the previous recommendation, the EBM criteria proposed by the Infectious Diseases Society of America (IDSA) are again employed throughout this document (Table 1). 15 Several newly introduced antifungal agents have been utilized in prophylaxis for the first time. These and other new studies have been incorporated into this updated guideline of the Infectious Diseases Working Party (AGIHO) of the German Society for Haematology and Oncology. The aim of this review is to provide the treating physician an up-to-date tool for the daily bedside decisions on primary antifungal prophylaxis. Objectives of antifungal prophylaxisIt is evident that the most relevant endpoint of antifungal prophylaxis is the reduction of mortality. However, death attributable to invasive fungal infection is difficult to prove and a reduction in overall mortality as a desirable endpoint of any clinical decision is difficult to achieve in the context of multiple competing illnesses in a severely immunocompromised host. Thus usually the reduction of the incidence rate of breakthrough invasive fungal infection is chosen as the primary endpoint of clinical trials. Improving rates of mucosal or other superficial infection and reducing colonization are no proper endpoints for antifungal prophylaxis with systemically active compounds. Design and MethodsThe guideline was prepared by a group of German clinicians. Systematic literature search comprised Medline, CancerLit, Embase, Cochrane Library and conference proceedings of Advances Against Aspergillosis, ASH, EBMT, ECCMID, ESMO, Focus on Fungal Infections, and ICAAC/IDSA, yielding a total of 86 clinical trials comprising 16,922 patients. Data extracted by OAC and MSi from each clinical study identifie...

show abstract

“…No hay, sin embargo, evaluaciones de anfotericina liposomal como profilaxis en pacientes receptores de TPH. Tampoco se ha evaluado en este grupo el uso de anfotericina liposomal en inhalación, sólo existen datos en un estudio vs placebo, controlado, en pacientes neutropénicos no sometidos a trasplantes, en que se evidenció disminución de la incidencia de aspergilosis pulmonar 67 .…”

Section: Uso En Casos Seleccionados Por Factores De Riesgounclassified

Profilaxis antifúngica en niños y adultos sometidos a trasplante de órganos sólidos y de precursores hematopoyéticos

Rabagliati¹,

Santolaya²

2012

Rev. chil. infectol.

View full text Add to dashboard Cite

Prophylaxis against fungal infections in solid organ and hematopoietic stem cells transplantationInvasive fungal infections are an important cause of morbidity and mortality in SOT and HSCT recipients. The main species involved are Candida spp. and Aspergillus spp, less frequently Cryptococcus spp., causal agents of mucormycosis and Fusarium spp. Usually occur within the first six months post-transplant, but they do it later, especially during episodes of rejection, which maintains the state of immune system involvement. Prophylaxis recommendations are specific to each type of transplant. In liver transplantation use of fluconazole is recommended only in selected cases by high risk factor for invasive fungal infections (A1). If the patient has a high risk of aspergillosis, there are some suggestions for adults population to use amphotericin B-deoxycholate, liposomal amphotericin B or caspofungin (C2) without being validated none of these recommendations in pediatric population. In adult lung transplant patients where the risk of aspergillosis is higher than in other locations, we recommend universal prophylaxis with itraconazole 200 mg/day, nebulised liposomal amphotericin B or voriconazole (C2), no validated recommendations for pediatrics. In HSCT, universal prophylaxis is recommended only in allogeneic and autologous selected cases. The most accepted indication is fluconazole (A1), and posaconazole (A1) or micafungin (A1) in selected cases with high risk of aspergillosis.Key words: Fungus, Candida, Aspergillus, yeasts, moulds, prophylaxis, amphotericin, fl uconazole, voriconaamphotericin, fluconazole, voriconazole, posaconazole, caspofungin, micafungin, transplants, solid organ transplantation, hematopoietic stem cells transplantation.Palabras clave: Hongos, Candida, Aspergillus, levaduras, hongos filamentosos, profilaxis, anfotericina, fluconazol, voriconazol, posaconazol, caspofungina, micafungina, trasplante, trasplante de órganos sólidos, trasplante de precursores hematopoyéticos. IntroducciónL as infecciones fúngicas constituyen una importante causa de morbilidad en los pacientes receptores de trasplantes de órganos sólidos (TOS) y trasplante de precursores hematopoyéticos (TPH) 1 , generando desafíos diagnósticos y terapéuticos, elevación de los costos de manejo y elevada mortalidad 2,3 . En los receptores de trasplantes, la enfermedad fúngica invasora (EFI) es provocada tanto por hongos levaduriformes como filamentosos, destacando Candida spp. y Aspergillus spp. 2-4 , menos frecuentemente Cryptococcus spp., agentes causales de mucormicosis 5,6 y Fusarium spp. 7 , infecciones por hongos endémicos como Histoplasma capsulatum, Coccidioides immitis, Paracoccidioides brasiliensis, y con menor cuantía dematiáceos como Cladosporium, Cladophialophora, Scopulariopsis, Alternaria, Curvularia y Bipolaris spp 8 .Existen diferencias en la frecuencia de EFI entre los distintos tipos de TOS y TPH; no obstante, algunas características son comunes: en ambos grupos la mayoría de las EFI son producidas por Candida spp. o ...

show abstract

Aerosolized Liposomal Amphotericin B for the Prevention of Invasive Pulmonary Aspergillosis during Prolonged Neutropenia: A Randomized, Placebo‐Controlled Trial

Abstract: In high-risk patients, prophylactic inhalation of liposomal amphotericin B significantly reduced the incidence of IPA.

Cited by 254 publications

References 19 publications

Addition of aerosolized deoxycholate amphotericin B to systemic prophylaxis to prevent airways invasive fungal infections in allogeneic hematopoietic SCT: a single-center retrospective study

Addition of aerosolized deoxycholate amphotericin B to systemic prophylaxis to prevent airways invasive fungal infections in allogeneic hematopoietic SCT: a single-center retrospective study

Primary prophylaxis of invasive fungal infections in patients with hematologic malignancies. Recommendations of the Infectious Diseases Working Party of the German Society for Haematology and Oncology

Profilaxis antifúngica en niños y adultos sometidos a trasplante de órganos sólidos y de precursores hematopoyéticos

Contact Info

Product

Resources

About