Terapia combinada de anfotericina B associada a caspofungina
Alguns modelos com camundongos e pequenos estudos clínicos têm descrito melhores desfechos com a anfotericina B e a caspofungina (um antifúngico da equinocandina), sobretudo em pacientes com diabetes com doença rino-órbito-cerebral.[65]Reed C, Bryant R, Ibrahim AS, et al. Combination polyene-caspofungin treatment of rhino-orbital-cerebral mucormycosis. Clin Infect Dis. 2008 Aug 1;47(3):364-71.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2793535
http://www.ncbi.nlm.nih.gov/pubmed/18558882?tool=bestpractice.com
[66]Spellberg B, Walsh TJ, Kontoyiannis DP, et al. Recent advances in the management of mucormycosis: from bench to bedside. Clin Infect Dis. 2009 Jun 15;48(12):1743-51.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2809216
http://www.ncbi.nlm.nih.gov/pubmed/19435437?tool=bestpractice.com
No entanto, estudos retrospectivos maiores, sobretudo em pacientes com neoplasia hematológica e receptores de transplantes com mucormicose pulmonar, não mostraram melhores desfechos.[67]Abidi MZ, Sohail MR, Cummins N, et al. Stability in the cumulative incidence, severity and mortality of 101 cases of invasive mucormycosis in high-risk patients from 1995 to 2011: a comparison of eras immediately before and after the availability of voriconazole and echinocandin-amphotericin combination therapies. Mycoses. 2014 Nov;57(11):687-98.
https://pmc.ncbi.nlm.nih.gov/articles/PMC4192082
http://www.ncbi.nlm.nih.gov/pubmed/25040241?tool=bestpractice.com
[68]Kyvernitakis A, Torres HA, Jiang Y, et al. Initial use of combination treatment does not impact survival of 106 patients with haematologic malignancies and mucormycosis: a propensity score analysis. Clin Microbiol Infect. 2016 Sep;22(9):811.e1-8.
https://www.clinicalmicrobiologyandinfection.com/article/S1198-743X(16)30047-7/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/27085727?tool=bestpractice.com
[69]Glampedakis E, Roth R, Masouridi-Levrat S, et al. Real-life considerations on antifungal treatment combinations for the management of invasive mold infections after allogeneic cell transplantation. J Fungi (Basel). 2021 Sep 28;7(10):811.
https://pmc.ncbi.nlm.nih.gov/articles/PMC8540382
http://www.ncbi.nlm.nih.gov/pubmed/34682233?tool=bestpractice.com
Mais pesquisas são necessárias para esclarecer o papel dessa combinação.[70]Meena DS, Kumar D, Bohra GK. Combination therapy in mucormycosis: current evidence from the world literature, a mini review. J Mycol Med. 2023 Mar;33(1):101332.
https://pmc.ncbi.nlm.nih.gov/articles/PMC9472709
http://www.ncbi.nlm.nih.gov/pubmed/36270213?tool=bestpractice.com
Administração localizada de anfotericina B
Relatos de caso descreveram a instilação endobrônquica de anfotericina B para o tratamento de mucormicose pulmonar.[71]Nattusamy L, Kalai U, Hadda V, et al. Bronchoscopic instillation of liposomal amphotericin B in management of nonresponding endobronchial mucormycosis. Lung India. 2017 Mar-Apr;34(2):208-9.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5351373
http://www.ncbi.nlm.nih.gov/pubmed/28360479?tool=bestpractice.com
[72]Alfageme I, Reina A, Gallego J, et al. Endobronchial instillations of amphotericin B: complementary treatment for pulmonary mucormycosis. J Bronchology Interv Pulmonol. 2009 Jul;16(3):214-5.
http://www.ncbi.nlm.nih.gov/pubmed/23168558?tool=bestpractice.com
O uso da suspensão oral de anfotericina B (que atua localmente no trato gastrintestinal) como parte da terapia combinada foi também descrito em um relato de caso no tratamento da infecção gastrointestinal localizada.[73]Anderson A, McManus D, Perreault S, et al. Combination liposomal amphotericin B, posaconazole and oral amphotericin B for treatment of gastrointestinal Mucorales in an immunocompromised patient. Med Mycol Case Rep. 2017 May 24;17:11-3.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5447657
http://www.ncbi.nlm.nih.gov/pubmed/28580237?tool=bestpractice.com
Pérolas de anfotericina B foram utilizadas com sucesso em um relato de caso de osteomielite por rhizopus.[74]Vashi N, Avedian R, Brown J, et al. Successful surgical and medical treatment of rhizopus osteomyelitis following hematopoietic cell transplantation. Orthopedics. 2012 Oct;35(10):e1556-61.
http://www.ncbi.nlm.nih.gov/pubmed/23027498?tool=bestpractice.com
É necessária mais pesquisa sobre estas novas formas de administrar anfotericina B.
Oxigenoterapia hiperbárica
Oxigenoterapia hiperbárica tem sido benéfica em certos relatos de caso, mas os dados não são adequados na ausência de grupos-controle para comparação.[12]Cornely OA, Alastruey-Izquierdo A, Arenz D, et al. Global guideline for the diagnosis and management of mucormycosis: an initiative of the European Confederation of Medical Mycology in cooperation with the Mycoses Study Group Education and Research Consortium. Lancet Infect Dis. 2019 Dec;19(12):e405-21.
https://pmc.ncbi.nlm.nih.gov/articles/PMC8559573
http://www.ncbi.nlm.nih.gov/pubmed/31699664?tool=bestpractice.com
[75]John BV, Chamilos G, Kontoyiannis DP. Hyperbaric oxygen as an adjunctive treatment for zygomycosis. Clin Microbiol Infect. 2005 Jul;11(7):515-7.
http://onlinelibrary.wiley.com/doi/10.1111/j.1469-0691.2005.01170.x/full
http://www.ncbi.nlm.nih.gov/pubmed/15966968?tool=bestpractice.com