DIAGNOSIS AND TREATMENT OF MUCORMYCOSIS: AN INTRUDER POST-COVID-19

Authors

DOI:

https://doi.org/10.22159/ajpcr.2023.v16i8.47828

Keywords:

Coronavirus disease 2019 associated mucormycosis, European confederation of medical mycology, Patents, Epidemiology, Therapy

Abstract

Mucormycosis can be elaborated as mycosis due to Mucorales. Mucormycosis is an angioinvasive infection. Fungi of Mucorales order is the causative organism of mucormycosis and pertains to the class of zygomycetes. It is ordered on number third after candidiasis and aspergillosis in the category of invasive mycosis. Rhizopus arrhizus (oryzae) is the most important species which cause this disease. It is categorized as a disease with high mortality. There is a 46% chance of mucormycosis with person having sinus infection, 76% of chances with pulmonary infection, and 96% for disseminated Mucormycosis. The COVID-19 pandemic precipitated this disease in a common way. Around 90% of the population was exposed to coronavirus disease 2019 (COVID-19) infection during the pandemic which ultimately affected the immunity of individual, leading to increased chance of exposure to other infectious disease. Mucormycosis is one of such disease which can highly affect the individual with COVID-19 infection in patient’s history. This review presents a brief about the disease origin, occurrences, types, signs and symptoms, risk factors, diagnosis, and treatments available, along with recent patents. This review also elaborated the treatment of COVID-19-associated mucormycosis and other risk factors. It was found that the diagnosis is not simple and easy sometimes it was observed postmortem also. This review also focuses on various methods with which easy diagnosis of this dreadful disease can be done.

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Author Biography

Disha Kesharwani, Department of , Columbia Institute of Pharmacy, Raipur, Chhattisgarh, India.

Assistant Professor,Department of Pharmacy,Columbia Institute of Pharmacy,Raipur

References

MoHFW, Ministry of Health and Family Welfare. Government of India. Available from: https://main.mohfw.gov.in/sites/default/files/

FinalforNetEnglishMoHFW040222.pdf [Last accessed on 2021 Jul 17].

Sharma S, Grover M, Bhargava S, Samdani S, Kataria T. Post coronavirus disease mucormycosis: A deadly addition to the pandemic spectrum. J Laryngol Otol 2021;135:442-7. doi: 10.1017/S0022215121000992, PMID 33827722

Saidha PK, Kapoor S, Das P, Gupta A, Kakkar V, Kumar A, et al. Mucormycosis of paranasal sinuses of odontogenic origin post

COVID19 infection: A case series. Indian J Otolaryngol Head Neck Surg 2021;74:1-5.

Rocha IC, Hasan MM, Goyal S, Patel T, Jain S, Ghosh A, et al. COVID-19 and mucormycosis syndemic: Double health threat to a collapsing healthcare system in India. Trop Med Int Health 2021;26:1016-8. doi: 10.1111/tmi.13641, PMID 34117677

Rodriguez-Morales AJ, Sah R, Millan-Oñate J, Gonzalez A, Montenegro- Idrogo JJ, Scherger S, et al. COVID-19 associated mucormycosis: The urgent need to reconsider the indiscriminate use of immunosuppressive drugs. Ther Adv Infect Dis 2021;8:20499361211027065. doi: 10.1177/20499361211027065, PMID 34211710

Alfishawy M, Elbendary A, Younes A, Negm A, Hassan WS, Osman SH, et al. Diabetes mellitus and coronavirus disease (Covid-19) Associated mucormycosis (CAM): A wake-up call from Egypt. Diabetes Metab Syndr Clin Res Rev 2021;15:102195. doi: 10.1016/j.dsx.2021.102195

Banerjee M, Pal R, Bhadada SK. Intercepting the deadly trinity of mucormycosis, diabetes and COVID-19 in India. Postgrad Med J 2022;98:e108-9. doi: 10.1136/postgradmedj-2021-140537

Raut A, Huy NT. Rising incidence of mucormycosis in patients with COVID-19: Another challenge for India amidst the second wave Lancet Respir Med 2021;9:e77. doi: 10.1016/S2213-2600(21)00265-4, PMID 34090607

Pandiar D, Kumar NS, Anand R, Kamboj M, Narwal A, Shameena PM, et al. Does COVID 19 generate a milieu for propagation of mucormycosis Med Hypotheses 2021;152:110613. doi: 10.1016/j. mehy.2021.110613, PMID 34087613

Paltauf A. Mycosis mucorina. Virchows Arch Pathol Anat Physiol Klin Med 1885;102:543.e64.

WHO. Diabetes Fact-Sheets; 2021. Available from: https://www. who.int/news-room/fact-sheets/detail/diabetes [Last accessed on 2021 May 26].

Baker RD. Mucormycosis-a new disease J Am Med Assoc 1957;163:805-8. doi: 10.1001/jama.1957.02970450007003

Eucker J, Sezer O, Graf B, Possinger K. Mucormycoses. Mycoses 2001;44:253-60. doi: 10.1111/j.1439- 0507.2001.00656.x, PMID 11714058

Prakash H, Chakrabarti A. Global epidemiology of mucormycosis. J Fungi (Basel) 2019;5:26. doi: 10.3390/jof5010026, PMID 30901907

International Diabetes Federation. IDF Diabetes Atlas. Available from: https://diabetesatlas.org/en/resources

Kwon-Chung KJ. Taxonomy of fungi causing mucormycosis and entomophthoramycosis (Zygomycosis) and nomenclature of the disease: Molecular mycologic perspectives. Clin Infect Dis 2012;54 Suppl 1:S8-15. doi: 10.1093/cid/cir864, PMID 22247451

Chibucos MC, Soliman S, Gebremariam T, Lee H, Daugherty S, Orvis J, et al. An integrated genomic and transcriptomic survey of mucormycosis-causing fungi. Nat Commun 2016;7:12218.

Suganya R, Malathi N, Karthikeyan V, Janagaraj VD. Mucormycosis: A brief review. J Pure Appl Microbiol 2019;13:161-5. doi: 10.22207/ JPAM.13.1.16

Spellberg B, Edwards J Jr., Ibrahim A. Novel perspectives on mucormycosis: Pathophysiology, presentation, and management. Clin Microbiol Rev 2005;18:556-69. doi: 10.1128/CMR.18.3.556-569.2005, PMID 16020690

Garcia-Covarrubias L, Bartlett R, Barratt DM, Wassermann RJ. Rhino-orbitocerebral mucormycosis attributable to Apophysomyces elegans in an immunocompetent individual: Case report and review of the literature. J Trauma 2001;50:353-7. doi: 10.1097/00005373- 200102000-00027, PMID 11242306

Stone N, Gupta N, Schwartz I. Mucormycosis: Time to address this deadly fungal infection. Lancet Microbe 2021;2:e343-4.

Times of India. Explained: Can Industrial Oxygen be Behind the Outbreak of Black Fungus; 2021. Available from: https://timesofindia. indiatimes.com/life-style/health-fitness/healthnews/black-fungus-causes-can-industrial-oxygen-be-behind-theoutbreak-of-black-fungus/ photostory/83035047.cms [Last accessed on 2021 Jun 16].

India Today. Can Spurt in Black Fungus cases be Blamed on Industrial Oxygen Cylinders, Dirty Water in Humidifiers; 2021. Available from: https://www.indiatoday.in/coronavirusoutbreak/ story/black-fungus-cases-industrial-oxygen-cylindershumidifiers-covid-19-1807099-2021-05-26 [Last accessed on 2021 Jun 16].

Bhatt K, Agolli A, Patel MH, Garimella R, Devi M, Garcia E, et al. High mortality co-infections of COVID-19 patients: Mucormycosis and other fungal infections. Discoveries (Craiova) 2021;9:e126. doi: 10.15190/d.2021.5, PMID 34036149

Sarkar S, Gokhale T, Choudhury SS, Deb AK. COVID-19 and orbital mucormycosis. Indian J Ophthalmol 2021;69:1002-4. doi: 10.4103/ijo. IJO_3763_20, PMID 33727483

Aggarwal D, Chander J, Janmeja AK, Katyal R. Pulmonary tuberculosis and mucormycosis co-infection in a diabetic patient. Lung India 2015;32:53-5. doi: 10.4103/0970-2113.148452, PMID 25624598

Chamilos G, Marom EM, Lewis RE, Lionakis MS, Kontoyiannis DP. Predictors of pulmonary Zygomycosis versus invasive pulmonary aspergillosis in patients with cancer. Clin Infect Dis 2005;41:60-6. doi: 10.1086/430710, PMID 15937764

Legouge C, Caillot D, Chrétien ML, Lafon I, Ferrant E, Audia S, et al. The reversed halo sign: Pathognomonic pattern of pulmonary mucormycosis in leukemic patients with neutropenia Clin Infect Dis 2014;58:672-8. doi: 10.1093/cid/cit929, PMID 24352351

Liu Y, Wu H, Huang F, Fan Z, Xu B. Utility of 18F- FDG PET/ CT in diagnosis and management of mucormycosis. Clin Nucl Med 2013;38:e370-1. doi: 10.1097/RLU.0b013e3182867d13, PMID 23531773

Frater JL, Hall GS, Procop GW. Histologic features of Zygomycosis: Emphasis on perineural invasion and fungal morphology. Arch Pathol Lab Med 2001;125:375-8. doi: 10.5858/2001-125-0375-HFOZ, PMID 11231486

Lass-Flörl C. Zygomycosis: Conventional laboratory diagnosis. Clin Microbiol Infect 2009;15 Suppl 5:60-5. doi: 10.1111/j.1469- 0691.2009.02999.x, PMID 19754760

Runwal P. A Rare Black Fungus is Infecting Many of India’s COVID-19 Patients-why Science, National Geography; 2021. Available from: https://www.nationalgeographic.co.uk/science-andtechnology/2021/05/a-rare-black-fungus-is-infecting-many-ofindias-covid-19-patients-why [Last accessed on 2021 May 26].

Monheit JE, Cowan DF, Moore DG. Rapid detection of fungi in tissues using Calcofluor white and fluorescence microscopy. Arch Pathol Lab Med 1984;108:616-8. PMID 6204621

Schrödl W, Heydel T, Schwartze VU, Hoffmann K, Grosse-Herrenthey A, Walther G, et al. Direct analysis and identification of pathogenic Lichtheimia species by matrix-assisted laser desorption ionization “Time of Flight” analyzer-mediated mass spectrometry. J Clin Microbiol 2012;50:419-27. doi: 10.1128/JCM.01070-11, PMID 22135259

Yang M, Lee JH, Kim YK, Ki CS, Huh HJ, Lee NY. Identification of Mucorales from clinical specimens: A 4-year experience in a single institution. Ann Lab Med 2016;36:60-3. doi: 10.3343/alm.2016.36.1.60, PMID 26522761

Schwarz P, Lortholary O, Dromer F, Dannaoui E. Carbon assimilation profiles as a tool for identification of zygomycetes. J Clin Microbiol 2007;45:1433-9. doi: 10.1128/JCM.02219-06, PMID 17329449

Sandven PE, Eduard W. Detection and quantitation of antibodies against Rhizopus by enzyme-linked immunosorbent assay. APMIS 1992;100:981-7. doi: 10.1111/j.1699-0463.1992.tb04029.x, PMID 1472367

Jones KW, Kaufman L. Development and evaluation of an immunodiffusion test for diagnosis of systemic Zygomycosis (mucormycosis): Preliminary report. J Clin Microbiol 1978;7:97-101. doi: 10.1128/jcm.7.1.97-101.1978

Hsiao CR, Huang L, Bouchara JP, Barton R, Li HC, Chang TC. Identification of medically important molds by an oligonucleotide array. J Clin Microbiol 2005;43:3760-8. doi: 10.1128/JCM.43.8.3760- 3768.2005, PMID 16081907

Machouart M, Larche J, Burton K, Collomb J, Maurer P, Cintrat A, et al. Genetic identification of the main opportunistic Mucorales by PCR-restriction fragment length polymorphism. J Clin Microbiol 2006;44:805-10.

Lackner M, Caramalho R, Lass-Flörl C. Laboratory diagnosis of mucormycosis: Current status and future perspectives. Future Microbiol 2014;9:683-95. doi: 10.2217/fmb.14.23, PMID 24957094

Sipsas NV, Gamaletsou MN, Anastasopoulou A, Kontoyiannis DP. Therapy of mucormycosis. J Fungi (Basel) 2018;4:90. doi: 10.3390/ jof4030090, PMID 30065232

Roden MM, Zaoutis TE, Buchanan WL, Knudsen TA, Sarkisova TA, Schaufele RL, et al. Epidemiology and outcome of Zygomycosis: A review of 929 reported cases. Clin Infect Dis 2005;41:634-53. doi: 10.1086/432579, PMID 16080086

Petrikkos G, Skiada A, Lortholary O, Roilides E, Walsh TJ, Kontoyiannis DP. Epidemiology and clinical manifestations of mucormycosis external. Clin Infect Dis 2012;54 Suppl 1:S23-34. doi: 10.1093/cid/cir866

Chegini Z, Didehdar M, Khoshbayan A, Rajaeih S, Salehi M, Shariati A. Epidemiology, clinical features, diagnosis and treatment of cerebral mucormycosis in diabetic patients: A systematic review of case reports and case series. Mycoses 2020;63:1264-82. doi: 10.1111/myc.13187, PMID 32965744

Malik VS, Ravindra K, Singh M. COVID-19 and increasing demand for medical oxygen: Can impurity be a problem Environ Sci Pollut Res Int 2021;28:66519-21. doi: 10.1007/s11356-021-16385-x, PMID 34535859

Gomes MZ, Lewis RE, Kontoyiannis DP. Mucormycosis caused by unusual mucormycetes, non-Rhizopus, -Mucor, and -Lichtheimia species. Clin Microbiol Rev 2011;24:411-45. doi: 10.1128/ CMR.00056-10, PMID 21482731

Ribes JA, Vanover-Sams CL, Baker DJ. Zygomycetes in human disease. Clin Microbiol Rev 2000;13:236-301. doi: 10.1128/CMR.13.2.236, PMID 10756000

Andresen D, Donaldson A, Choo L, Knox A, Klaassen M, Ursic C, et al. Multifocal cutaneous mucormycosis complicating polymicrobial wound infections in a tsunami survivor from Sri Lanka. Lancet 2005;365:876-8. doi: 10.1016/S0140-6736(05)71046-1, PMID 15752532

Rao CY, Kurukularatne C, Garcia-Diaz JB, Kemmerly SA, Reed D, Fridkin SK, et al. Implications of detecting the mold Syncephalastrum in clinical specimens of New Orleans residents after hurricanes Katrina and Rita. J Occup Environ Med 2007;49:411-6. doi: 10.1097/ JOM.0b013e31803b94f9, PMID 17426524

Fanfair RN, Benedict K, Bos J, Bennett SD, Lo YC, Adebanjo T, et al. Necrotizing cutaneous mucormycosis after a Tornado in Joplin, Missouri, in 2011. N Engl J Med 2012;367:2214-25. doi: 10.1056/ NEJMoa1204781, PMID 23215557

Boelaert JR, Van Cutsem J, De Locht M, Schneider YJ, Crichton RR. Deferoxamine augments growth and pathogenicity of Rhizopus, while hydroxypyridinone chelators have no effect. Kidney Int 1994;45:667-71. doi: 10.1038/ki.1994.89, PMID 8196268

De Locht M, Boelaert JR, Schneider YJ. Iron uptake from ferrioxamine and from ferrirhizoferrin by germinating spores of Rhizopus microsporus. Biochem Pharmacol 1994;47:1843-50. doi: 10.1016/0006-2952(94)90314-x, PMID 8204101

Boelaert JR, Fenves AZ, Coburn JW. Deferoxamine therapy and mucormycosis in dialysis patients: Report of an international registry. Am J Kidney Dis 1991;18:660-7. doi: 10.1016/s0272- 6386(12)80606-8, PMID 1962650

Maertens J, Demuynck H, Verbeken EK, Zachée P, Verhoef GE, Vandenberghe P, et al. Mucormycosis in allogeneic bone marrow transplant recipients: Report of five cases and review of the role of iron overload in the pathogenesis. Bone Marrow Transplant 1999;24:307-12. doi: 10.1038/sj.bmt.1701885, PMID 10455371

Lelievre L, Garcia-Hermoso D, Abdoul H, Hivelin M, Chouaki T, Toubas D, et al. Posttraumatic mucormycosis: A nationwide study in France and review of the literature. Medicine (Baltimore) 2014;93:395- 404. doi: 10.1097/MD.0000000000000221, PMID 25500709

Davoudi S, Kumar VA, Jiang Y, Kupferman M, Kontoyiannis DP. Invasive mould sinusitis in patients with haematological malignancies: A 10 year single-centre study. J Antimicrob Chemother 2015;70:2899- 905. doi: 10.1093/jac/dkv198, PMID 26188039

Farmakiotis D, Kontoyiannis DP. Mucormycoses. Infect Dis Clin N Am 2016;30:143-63. doi: 10.1016/j.idc.2015.10.011, PMID 26897065

Spellberg B, Fu Y, Edwards JE Jr., Ibrahim AS. Combination therapy with Amphotericin B Lipid Complex and caspofungin acetate of disseminated Zygomycosis in diabetic ketoacidotic mice. Antimicrob Agents Chemother 2005;49:830-2. doi: 10.1128/ AAC.49.2.830-832.2005, PMID 15673781

Ibrahim AS, Gebremariam T, Fu Y, Edwards JE Jr., Spellberg B. Combination echinocandin-polyene treatment of murine mucormycosis. Antimicrob Agents Chemother 2008;52:1556-8. doi: 10.1128/ AAC.01458-07, PMID 18212099

Legrand M, Gits-Muselli M, Boutin L, Garcia-Hermoso D, Maurel V, Soussi S, et al. Detection of circulating Mucorales DNA in critically ill burn patients: Preliminary report of a screening strategy for early diagnosis and treatment. Clin Infect Dis 2016;63:1312-7. doi: 10.1093/ cid/ciw563, PMID 27535951

Rudramurthy SM, Hoenigl M, Meis JF, Cornely OA, Muthu V, Gangneux JP, et al. ECMM/ISHAM recommendations for clinical management of COVID‐19 associated mucormycosis in low‐and middle‐income countries. Mycoses 2021;64:1028-7. Skiada A, Petrikkos G. Cutaneous mucormycosis. Skinmed 2013;11:155-9; quiz 159. PMID 23930354

Davoudi S, Graviss LS, Kontoyiannis DP. Healthcare-associated outbreaks due to Mucorales and other uncommon fungi. Eur J Clin Invest 2015;45:767-73.

Astellas Pharma US. Prescribing Information for Isavuconazonium Sulfate. Available from: https://www.astellas.us/docs/cresemba.pdf [Last accessed on 2018 Jul 01].

Rodríguez MM, Serena C, Mariné M, Pastor FJ, Guarro J. Posaconazole combined with amphotericin B, an effective therapy for a murine-disseminated infection caused by Rhizopus oryzae. Antimicrob Agents Chemother 2008;52:3786-8. doi: 10.1128/AAC.00628-08, PMID 18694953

Ibrahim AS, Gebremariam T, Schwartz JA, Edwards JE Jr., Spellberg B. Posaconazole mono-or combination therapy for the treatment of murine Zygomycosis. Antimicrob Agents Chemother 2009;53:772-5. doi: 10.1128/AAC.01124-08, PMID 18936190

Abzug MJ, Walsh TJ. Interferon-γ and colony-stimulating factors as adjuvant therapy for refractory fungal infections in children. Pediatr Infect Dis J 2004;23:769-73. doi: 10.1097/01.inf.0000134314.65398. bf, PMID 15295229

Gonzalez CE, Couriel DR, Walsh TJ. Disseminated zygomycosis in a neutropenic patient: Successful treatment with amphotericin B Lipid complex and granulocyte colony-stimulating factor. Clin Infect Dis 1997;24:192-6. doi: 10.1093/clinids/24.2.192, PMID 9114146

Kullberg BJ, Anaissie EJ. Cytokines as therapy for opportunistic fungal infections. Res Immunol 1998;149:478-88; discussion 515. doi: 10.1016/s0923-2494(98)80771-2, PMID 9720965

Ma B, Seymour JF, Januszewicz H, Slavin MA. Cure of pulmonary Rhizomucor pusillus infection in a patient with hairy-cell leukemia: Role of liposomal amphotericin B and GM-CSF. Leuk Lymphoma 2001;42:1393-9. doi: 10.3109/10428190109097768, PMID 11911424

Ibrahim AS, Liu M. Teklegiorgis Ghebremariam. In: Fu Y, Edwards JE, Filler S, editors. Use of Coth for Immunotherapy and Diagnosis of Mucormycosis. US20190194301A1. US: ???; 2019.

Luppi M, Barozzi P, Potenza L, Vallerini D, Forghieri F. Procedure for diagnosing and monitoring mucormycosis. Europe. EP2646829A1, 2013.

Ibrahim AS, Spielberg BJ, Edwards JE. Treatment method for mucormycosis and other epiphyte diseases, CN101511360A, China, 2009.

Ibrahim AS, Spielberg BJ, Edwards JE. Composition of vaccine for mucormycosis. CN102639557A, China, 2012.

Ibrahim AS, Spellberg BJ, Edwards JE. Use of the Combination of Iron Chelator and Antifungal Agent for the Treatment of Mucormycosis. New Zealand; 2012. p. NZ574862A.

Chibana H, Chika H, Chibana H. Mucormycosis treatment agent. JP2021134176A, Japan, 2021.

Bruno V, Watkins TN, Ibrahim A. Approach for Prevention and Treatment of Mucormycosis. US20210284742A1. United State: Centers for Disease Control and Prevention; 2021.

Dongxiu S, Jingjia C. Method of preparation of feed for treating mucormycosis of Cyclemys trifasciata. CN104872438A, China; 2015.

Kakeya H, Kaneko Y, Miyazaki Y, Yamagoe S. Tools and methods for diagnosing/testing mucormycosis, JP6742611B2, Japan; 2020.

Spellberg BJ, Edwards JE, Ibrahim AS. Compositions and methods for the treatment of mucormycosis and other fungal diseases. BRPI0714221A2, Brazil; 2013.

Published

07-08-2023

How to Cite

Kesharwani, D., S. Mishra, B. Verma, K. Verma, and Suraj Banjare. “DIAGNOSIS AND TREATMENT OF MUCORMYCOSIS: AN INTRUDER POST-COVID-19”. Asian Journal of Pharmaceutical and Clinical Research, vol. 16, no. 8, Aug. 2023, pp. 24-29, doi:10.22159/ajpcr.2023.v16i8.47828.

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Review Article(s)