Amphotericin-B plus caspofungin combination therapy
Some mouse models and small clinical studies have described improved outcomes with amphotericin-B and caspofungin (an echinocandin antifungal), particularly in patients with diabetes with rhino-orbital cerebral disease.[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
However, larger retrospective studies, particularly patients with haematological malignancy and transplant recipients with pulmonary mucormycosis, did not show improved outcomes.[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
Further research is needed to clarify the role of this combination.[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
Localised administration of amphotericin-B
Case reports have described endobronchial instillation of amphotericin-B for the treatment of pulmonary mucormycosis.[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
Use of oral amphotericin-B suspension (which acts locally in the gastrointestinal tract) as part of combination therapy has also been described in one case report in the treatment of localised gastrointestinal infection.[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
Amphotericin-B beads have been used successfully in one case report of rhizopus osteomyelitis.[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
More research is needed on these novel ways of administering amphotericin-B.
Hyperbaric oxygen therapy
Hyperbaric oxygen therapy has been beneficial in certain case reports, but data are not adequate in the absence of control groups for comparison.[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