Utility of Itraconazole in Combination with Liposomal Amphotericin B in Rhizopus oryzae Associated Mucormycosis-An Exploratory Study.
Amphotericin B
Antifungals
COVID-19
Diabetes
Itraconazole
Mucormycosis
Pandemic
Rhino-orbito-cerebral mucormycosis
Journal
Mycopathologia
ISSN: 1573-0832
Titre abrégé: Mycopathologia
Pays: Netherlands
ID NLM: 7505689
Informations de publication
Date de publication:
12 Jun 2024
12 Jun 2024
Historique:
received:
03
03
2024
accepted:
07
05
2024
medline:
12
6
2024
pubmed:
12
6
2024
entrez:
12
6
2024
Statut:
epublish
Résumé
During the COVID-19 pandemic-associated mucor epidemic, acute antifungal drug shortage necessitated the exploration of other antifungals based on culture sensitivity. Itraconazole is a cheap, safe, and effective antifungal in sensitive cases. We enrolled itraconazole-sensitive COVID-19-associated mucormycosis during the mucormycosis pandemic. After the intensive phase course of liposomal amphotericin B, Itraconazole was offered in susceptible cases during the maintenance phase along with standard of care. These patients were clinically and radiologically followed for 6 months. We enrolled 14 patients (Male: Female-11:3) of Rhino-orbito-cerebral mucormycosis (ROCM) which included 12 diabetics. All patients had facial swelling, orbital swelling, visual impairment, and headache. MRI showed involvement of bilateral sinus (10/14), orbital extension (13/14), cavernous sinus (5/14), cerebral part of the internal carotid artery (3/14), and brain infarcts (4/14). All 14 patients showed sensitivity to Itraconazole with 12 having minimum inhibitory concentration (MIC) ≤ 1 μg/ml and 2 having MIC ≤ 2 μg/ml. Follow-up at 6 months showed clinical improvement in the majority (11/14) and radiological improvement in six out of seven scanned patients. Our study shows the potential therapeutic role of oral Itraconazole in ROCM.
Sections du résumé
BACKGROUND
BACKGROUND
During the COVID-19 pandemic-associated mucor epidemic, acute antifungal drug shortage necessitated the exploration of other antifungals based on culture sensitivity. Itraconazole is a cheap, safe, and effective antifungal in sensitive cases.
METHODOLOGY
METHODS
We enrolled itraconazole-sensitive COVID-19-associated mucormycosis during the mucormycosis pandemic. After the intensive phase course of liposomal amphotericin B, Itraconazole was offered in susceptible cases during the maintenance phase along with standard of care. These patients were clinically and radiologically followed for 6 months.
RESULTS
RESULTS
We enrolled 14 patients (Male: Female-11:3) of Rhino-orbito-cerebral mucormycosis (ROCM) which included 12 diabetics. All patients had facial swelling, orbital swelling, visual impairment, and headache. MRI showed involvement of bilateral sinus (10/14), orbital extension (13/14), cavernous sinus (5/14), cerebral part of the internal carotid artery (3/14), and brain infarcts (4/14). All 14 patients showed sensitivity to Itraconazole with 12 having minimum inhibitory concentration (MIC) ≤ 1 μg/ml and 2 having MIC ≤ 2 μg/ml. Follow-up at 6 months showed clinical improvement in the majority (11/14) and radiological improvement in six out of seven scanned patients.
CONCLUSION
CONCLUSIONS
Our study shows the potential therapeutic role of oral Itraconazole in ROCM.
Identifiants
pubmed: 38865003
doi: 10.1007/s11046-024-00859-w
pii: 10.1007/s11046-024-00859-w
doi:
Substances chimiques
Itraconazole
304NUG5GF4
Amphotericin B
7XU7A7DROE
Antifungal Agents
0
liposomal amphotericin B
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
54Informations de copyright
© 2024. The Author(s), under exclusive licence to Springer Nature B.V.
Références
Malhotra HS, Gupta P, Mehrotra D, Dandu H, Kohli N, Verma V, Kaur A, Kumar N, Prabhu V, Singh MK, Jaiswal R. COVID-19 associated mucormycosis: staging and management recommendations (Report of a multi-disciplinary expert committee). J Oral Biol Craniofac Res. 2021;11(4):569–80. https://doi.org/10.1016/j.jobcr.2021.08.001 .
doi: 10.1016/j.jobcr.2021.08.001
pubmed: 34395187
pmcid: 8354814
Brunet K, Rammaert B. Mucormycosis treatment: recommendations, latest advances, and perspectives. J de mycologie med. 2020;30(3):101007. https://doi.org/10.1016/j.mycmed.2020.101007 .
doi: 10.1016/j.mycmed.2020.101007
Zhang T, Shen Y, Feng S. Clinical research advances of isavuconazole in the treatment of invasive fungal diseases. Front Cell Infect Microbiol. 2022;1(12):1049959. https://doi.org/10.3389/fcimb.2022.1049959 .
doi: 10.3389/fcimb.2022.1049959
Shirley M, Scott LJ. Isavuconazole: a review in invasive aspergillosis and mucormycosis. Drugs. 2016;76:1647–57. https://doi.org/10.1007/s40265-016-0652-6 .
doi: 10.1007/s40265-016-0652-6
pubmed: 27766566
Chaudhari HS, Palkar OS, Abha Mishra KM, Sethi KK. An extensive review on antifungal approaches in the treatment of mucormycosis. J Biochem Mol Toxicol. 2023;22:e23417. https://doi.org/10.1002/jbt.23417 .
doi: 10.1002/jbt.23417
Lynch JP III, Zhanel GG. Part 2: Mucormycosis: focus on therapy. Expert Rev Anti Infect Ther. 2023;21(7):737–48. https://doi.org/10.1080/14787210.2023.2224564 .
doi: 10.1080/14787210.2023.2224564
pubmed: 37300820
Bagshaw E, Kuessner D, Posthumus J, Escrig C, Blackney M, Heimann SM, Cornely OA. The cost of treating mucormycosis with isavuconazole compared with standard therapy in the UK. Future Microbiol. 2017;12(6):515–25. https://doi.org/10.2217/fmb-2016-0231 .
doi: 10.2217/fmb-2016-0231
pubmed: 28191796
Bellmann R, Smuszkiewicz P. Pharmacokinetics of antifungal drugs: practical implications for optimized treatment of patients. Infection. 2017;45:737–79. https://doi.org/10.1007/s15010-017-1042-z .
doi: 10.1007/s15010-017-1042-z
pubmed: 28702763
pmcid: 5696449
Cauwenbergh G. Cryptococcal meningitis: the place of itraconazole. Mycoses. 1993;36(7–8):221–8. https://doi.org/10.1111/j.1439-0507.1993.tb00755.x .
doi: 10.1111/j.1439-0507.1993.tb00755.x
pubmed: 8114801
Eisen DP, Robson J. Complete resolution of pulmonary Rhizopus oryzae infection with itraconazole treatment: more evidence of the utility of azoles for zygomycosis. Mycoses. 2004;47(3–4):159–62. https://doi.org/10.1111/j.1439-0507.2004.00959.x .
doi: 10.1111/j.1439-0507.2004.00959.x
pubmed: 15078434
Ganesh R, Manikumar S, Vasanthi T. Rhinocerebral mucormycosis in an adolescent with type 1 diabetes mellitus: case report. Ann Trop Paediatr. 2008;28(4):297–300. https://doi.org/10.1179/146532808X375477 .
doi: 10.1179/146532808X375477
pubmed: 19021947
Parthiban K, Gnanaguruvelan S, Janaki C, Sentamilselvi G, Boopalraj JM. Rhinocerebral zygomycosis: Rhinozerebrale zygomykose. Mycoses. 1998;41(1–2):51–3. https://doi.org/10.1111/j.1439-0507.1998.tb00376.x .
doi: 10.1111/j.1439-0507.1998.tb00376.x
pubmed: 9610134
Jiang N, Zhao G, Yang S, Lin J, Hu L, Che C, Wang Q, Xu Q. A retrospective analysis of eleven cases of invasive rhino-orbito-cerebral mucormycosis presented with orbital apex syndrome initially. BMC Ophthalmol. 2016;16:1–7. https://doi.org/10.1186/s12886-016-0189-1 .
doi: 10.1186/s12886-016-0189-1
Gupta P, Malhotra HS, Saxena P, Singh R, Shukla D, Hasan MS, Verma V, Banerjee G, Puri B, Dandu H. Utility of itraconazole and terbinafine in mucormycosis: a proof-of-concept analysis. J Investig Med. 2022;70(4):914–8. https://doi.org/10.1136/jim-2021-002179 .
doi: 10.1136/jim-2021-002179
pubmed: 35078866
Heykants J, Van Peer A, Van de Velde V, Van Rooy P, Meuldermans W, Lavrijsen K, Woestenborghs R, Van Cutsem J, Cauwenbergh G. The clinical pharmacokinetics of itraconazole: an overview. Mycoses. 1989;32:67–87. https://doi.org/10.1111/j.1439-0507.1989.tb02296.x .
doi: 10.1111/j.1439-0507.1989.tb02296.x
pubmed: 2561187
Denning DW, Tucker RM, Hanson LH, Hamilton JR, Stevens DA. Itraconazole therapy for cryptococcal meningitis and cryptococcosis. Arch Intern Med. 1989;149(10):2301–8.
doi: 10.1001/archinte.1989.00390100107024
pubmed: 2552949
Diekema DJ, Messer SA, Hollis RJ, Jones RN, Pfaller MA. Activities of caspofungin, itraconazole, posaconazole, ravuconazole, voriconazole, and amphotericin B against 448 recent clinical isolates of filamentous fungi. J Clin Microbiol. 2003;41(8):3623–6. https://doi.org/10.1128/JCM.41.8.3623-3626.2003 .
doi: 10.1128/JCM.41.8.3623-3626.2003
pubmed: 12904365
pmcid: 179829
Pfaller MA, Messer SA, Hollis RJ, Jones RN. Antifungal activities of posaconazole, ravuconazole, and voriconazole compared to those of itraconazole and amphotericin B against 239 clinical isolates of Aspergillus spp. and other filamentous fungi: report from SENTRY Antimicrobial surveillance program, 2000. Antimicrob agents chemother. 2002;46(4):1032–7. https://doi.org/10.1128/AAC.46.4.1032-1037.2002 .
doi: 10.1128/AAC.46.4.1032-1037.2002
pubmed: 11897586
pmcid: 127116
Taneja J, Chatterjee K, Sasidharan J, Abbas SZ, Rai AK, Raychaudhury S, Das B, Das A. Post-COVID-19 rhino-orbito-cerebral mucormycosis–A clinico-mycological study from North India. Med Mycol. 2023;61(7):myad067. https://doi.org/10.1093/mmy/myad067 .
doi: 10.1093/mmy/myad067
pubmed: 37442616
Cham CY, Radhakrishnan AP, Chang CY. Successful treatment of mucormycosis caused by Rhizopus arrhizus with amphotericin B and itraconazole. Cureus. 2023. https://doi.org/10.7759/cureus.35814 .
doi: 10.7759/cureus.35814
pubmed: 37033497
pmcid: 10074751