Prospective pilot study of high-dose (10 mg/kg/day) liposomal amphotericin B (L-AMB) for the initial treatment of mucormycosis

Autor: Benoit Guery, Pierre BUFFET, Stéphane Bretagne, Frédéric GRENOUILLET, Benjamin Wyplosz, Tristan Ferry, André Paugam, Yvon STERKERS, Sophie Cassaing, Philippe Moreau, Anne-Lise Bienvenu, Raoul Herbrecht, Anne Thiebaut-Bertrand, Mathilde Hunault, Cedric Arvieux, Jean-Pierre Gangneux, Boualem Sendid, Olivia Freynet
Přispěvatelé: Pathogénie des infections systémiques (UMR_S 570), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de Radiologie et imagerie médicale [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut de génétique et microbiologie [Orsay] (IGM), Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), Mycologie moléculaire, Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], Service d’Oncologie et d’Hématologie, Hôpitaux Universitaires de Strasbourg, Strasbourg, France, Space Science Institute [Boulder] (SSI), Service greffe de moelle osseuse, Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre d'infectiologie Necker-Pasteur [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut Pasteur [Paris], This work was supported by a grant from Gilead Sciences, but the sponsor took no part in the scientific evaluation. L-AMB was kindly provided by Gilead Sciences., We thank Assistance Publique-Hôpitaux de Paris, promoter of the study. We thank URC Paris Descartes Necker (Beatrice Barbier) for the implementation, monitoring and data management of the study. We also thank Eric Dannaoui and Michel Huerre for their help in isolate collection and pathological slide reviews and Susan DeWolf for her helpful comments prior to submission. We thank Muriel Vray, Michel Tod, Vincent Jullien, Agnes Lefort and Caroline Charlier-Woerther for their participation in the safety committee., Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Institut Pasteur [Paris] (IP)-CHU Necker - Enfants Malades [AP-HP], Institut Pasteur [Paris]-CHU Necker - Enfants Malades [AP-HP], Imagine - Institut des maladies génétiques (IMAGINE - U1163), Unité de recherche clinique / Centre d'investigation clinique [CHU Necker], Centre National de Référence des Mycoses invasives et antifongiques - Mycologie moléculaire (CNRMA), Hôpital de Hautepierre [Strasbourg], AP-HP - Hôpital Bichat - Claude Bernard [Paris]
Jazyk: angličtina
Rok vydání: 2015
Předmět:
Male
Antifungal Agents
[SDV]Life Sciences [q-bio]
Pilot Projects
MESH: Mucormycosis/surgery
Gastroenterology
chemistry.chemical_compound
Amphotericin B
MESH: Child
Pharmacology (medical)
Prospective Studies
Child
Prospective cohort study
[SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology
MESH: Treatment Outcome
Response rate (survey)
MESH: Aged
MESH: Middle Aged
Incidence (epidemiology)
Middle Aged
MESH: Infant
3. Good health
Treatment Outcome
Infectious Diseases
MESH: Young Adult
Child
Preschool
Female
medicine.drug
Adult
Microbiology (medical)
medicine.medical_specialty
Adolescent
MESH: Amphotericin B/administration & dosage
MESH: Mucormycosis/drug therapy
Young Adult
Internal medicine
medicine
Humans
Mucormycosis
MESH: Debridement
Aged
MESH: Antifungal Agents/administration & dosage
Pharmacology
MESH: Adolescent
Creatinine
MESH: Humans
business.industry
MESH: Child
Preschool
Infant
MESH: Adult
medicine.disease
MESH: Pilot Projects
MESH: Male
MESH: Prospective Studies
Surgery
Clinical trial
Regimen
Debridement
chemistry
business
MESH: Female
Zdroj: Journal of Antimicrobial Chemotherapy
Journal of Antimicrobial Chemotherapy, Oxford University Press (OUP), 2015, 70 (11), pp.3116-3123. ⟨10.1093/jac/dkv236⟩
Journal of Antimicrobial Chemotherapy, 2015, 70 (11), pp.3116-3123. ⟨10.1093/jac/dkv236⟩
ISSN: 0305-7453
1460-2091
DOI: 10.1093/jac/dkv236⟩
Popis: International audience; Background: Mucormycosis incidence is increasing and is associated with a high rate of mortality. Although lipid-based formulations of amphotericin B are the recommended first-line treatment, only one prospective trial in a limited number of patients has been performed to evaluate this regimen. Methods: Patients with proven or probable mucormycosis were included between June 2007 and March 2011. Patients were scheduled to receive 10 mg/kg/day liposomal amphotericin B (L-AMB) monotherapy for 1 month and surgery was performed when appropriate. The primary outcome was response rate at week 4 or at the end of treatment (EOT) if before week 4, evaluated by an independent committee. ClinicalTrials.gov Identifier: NCT00467883. Results: Forty patients were enrolled. Response was analysed in 33 patients at week 4. Most patients had a haem-atological malignancy as their primary underlying disease (53%). Seventy-one percent of patients underwent therapeutic surgery. The response rate at week 4 or at EOT was 36%, with 18% partial responses and 18% complete responses. The response rate at week 12 was 45%, with 13% partial responses and 32% complete responses. Overall mortality was 38% at week 12 and 53% at week 24. Serum creatinine doubled in 16 (40%) patients and returned to normal levels within 12 weeks in 10/16 (63%). Conclusions: High-dose LAMB for mucormycosis, in combination with surgery in 71% of cases, was associated with an overall response rate of 36% at week 4 and 45% at week 12 and creatinine level doubling in 40% of patients (transient in 63%). These results may serve as the basis for future clinical trials.
Databáze: OpenAIRE
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