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

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  • معلومة اضافية
    • Contributors:
      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; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Necker - Enfants Malades 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; Institut Pasteur Paris (IP)-Centre National de la Recherche Scientifique (CNRS); Les Hôpitaux Universitaires de Strasbourg (HUS); Space Science Institute Boulder (SSI); Service greffe de moelle osseuse; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal Paris; Centre d'infectiologie Necker-Pasteur CHU Necker; Institut Pasteur Paris (IP)-Hôpital Necker - Enfants Malades AP-HP; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP); 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.
    • بيانات النشر:
      HAL CCSD
      Oxford University Press (OUP)
    • الموضوع:
      2015
    • Collection:
      Institut Pasteur: HAL
    • نبذة مختصرة :
      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.
    • Relation:
      info:eu-repo/semantics/altIdentifier/pmid/26316385; hal-02317920; https://normandie-univ.hal.science/hal-02317920; https://normandie-univ.hal.science/hal-02317920/document; https://normandie-univ.hal.science/hal-02317920/file/lanternier2015%20%281%29.pdf; PUBMED: 26316385
    • الرقم المعرف:
      10.1093/jac/dkv236
    • Rights:
      info:eu-repo/semantics/OpenAccess
    • الرقم المعرف:
      edsbas.E93487F