DOI: http://dx.doi.org/10.18203/issn.2454-5929.ijohns20212336

Breaking the mold: a brief review on the diagnostic and treatment approaches of mucormycosis

Aroop Mohanty, Pratima Gupta, Saurabh Varshney, Ankita Kabi, Sumeet Angral

Abstract


Mucormycosis is a severe emerging angioinvasive fungal infection that occurs predominantly in immunocompromised individuals. The incidence of this disease seems to be increasing in recent years with the emergence of new causative agents and rise of the susceptible population. The present COVID-19 pandemic has seen an un-precented increase in the number of mucormycosis cases all over the world. It has emerged as one of the most common complication of COVID-19 leading to severe morality. Uncontrolled diabetes has been postulated to be the most common underlying disease in developing countries and hematological malignancies in case of the high-income countries. Besides diabetes, chronic renal failure and tuberculosis have also been predisposed in the Indian subcontinent. Rhino-cerebral form is mostly seen in diabetics whereas the pulmonary type is the most common presentation in patients with hematological malignancies and solid organ transplant. Diagnosis and treatment of this rapidly progressive disease is equally challenging. Microscopy and culture are the cornerstone for the diagnosis, but if assisted by imaging and molecular assays, it plays an important role in the correct and early identification of the causative agent. Successful management of mucormycosis is based on an integrated approach, including reversal or discontinuation of underlying risk factors, early administration of antifungal agents, and complete removal of infected tissue and use of various adjunctive therapies.


Keywords


Mucormycosis, Aseptate hyphae, Mucoraeles, Diabetes mellitus

Full Text:

PDF

References


Prakash H, Ghosh AK, Rudramurthy SM, Singh P, Xess I, Savio J, et al. A prospective multicenter study on mucormycosis in India: Epidemiology, diagnosis, and treatment. Med Mycol. 2019;57(4):395-402.

Chung KJ. Taxonomy of fungi causing mucormycosis and entomophthoramycosis (zygomycosis) and nomenclature of the disease: molecular mycologic perspectives. Clin Infect Dis. 2012;54(1):8-15.

Richardson M. The ecology of the Zygomycetes and its impact on environmental exposure. Clin Microbiol Infect. 2009;15(5):2-9.

Jeong W, Keighley C, Wolfe R, Lee WL, Slavin MA, Kong DCM, et al. The epidemiology and clinical manifestations of mucormycosis: a systematic review and meta-analysis of case reports. Clin Microbiol Infect. 2019;25(1):26-34.

Prakash H, Chakrabarti A. Global Epidemiology of Mucormycosis. J Fungi. 2019;5(1):26.

Saegeman V, Maertens J, Meersseman W, Spriet I, Verbeken E, Lagrou K. Increasing incidence of mucormycosis in University Hospital, Belgium. Emerg Infect Dis. 2010;16(9):1456-8.

Guinea J, Escribano P, Vena A, Munoz P, Martínez JMDC, Padilla B, Bouza E. Increasing incidence of mucormycosis in a large Spanish hospital from 2007 to 2015: Epidemiology and microbiological characterization of the isolates. PLoS One. 2017;12(6):179136.

Chakrabarti A, Chatterjee SS, Das A, Panda N, Shivaprakash MR, Kaur A, et al. Invasive zygomycosis in India: experience in a tertiary care hospital. Postgrad Med J. 2009;85(1009):573-81.

Skiada A, Rigopoulos D, Larios G, Petrikkos G, Katsambas A. Global epidemiology of cutaneous zygomycosis. Clin Dermatol. 2012; 30: 628-632.

Chakrabarti A, Das A, Mandal J, Shivaprakash MR, George VK, Tarai B, Rao P, et al. The rising trend of invasive zygomycosis in patients with uncontrolled diabetes mellitus. Med Mycol. 2006;44(4):335-42.

Kontoyiannis DP, Yang H, Song J, Kelkar SS, Yang X, Azie N, et al. Prevalence, clinical and economic burden of mucormycosis-related hospitalizations in the United States: a retrospective study. BMC Infect Dis. 2016;16(1):730.

Lamaris GA, Ben AR, Lewis RE, Chamilos G, Samonis G, Kontoyiannis DP. Increased virulence of Zygomycetes organisms following exposure to voriconazole: a study involving fly and murine models of zygomycosis. J Infect Dis. 2009;199(9):1399-406.

Rammaert B, Lanternier F, Zahar JR, Dannaoui E, Bougnoux ME, Lecuit M, et al. Healthcare-associated mucormycosis. Clin Infect Dis. 2012;54(1):44-54.

Mohanty A, Kabi A, Mohanty AP. Health problems in healthcare workers: A review. J Family Med Prim Care. 2019;8(8):2568-72.

Chakrabarti A, Das A, Sharma A, Panda N, Das S, Gupta KL, Sakhuja V. Ten years' experience in zygomycosis at a tertiary care centre in India. J Infect. 2001;42(4):261-6.

Dolatabadi S, Ahmadi B, Rezaei MA, Zarrinfar H, Skiada A, Mirhendi H, et al. Mucormycosis in Iran: A six-year retrospective experience. J Mycol Med. 2018;28(2):269-73.

Kennedy KJ, Daveson K, Slavin MA, Hal SJ, Sorrell TC, Lee A, et al. Mucormycosis in Australia: contemporary epidemiology and outcomes. Clin Microbiol Infect. 2016;22(9):775-81.

Komur S, Inal AS, Kurtaran B, Ulu A, Uguz A, Aksu HS, Taşova Y. Mucormycosis: a 10-year experience at a tertiary care center in Turkey. Turk J Med Sci. 2016;46(1):58-62.

Zilberberg MD, Shorr AF, Huang H, Chaudhari P, Paly VF, Menzin J. Hospital days, hospitalization costs, and inpatient mortality among patients with mucormycosis: a retrospective analysis of US hospital discharge data. BMC Infect Dis. 2014;14:310.

Zaki SM, Elkholy IM, Elkady NA, Abdel GK. Mucormycosis in Cairo, Egypt: review of 10 reported cases. Med Mycol. 2014;52(1):73-80.

Petrikkos G, Skiada A, Sambatakou H, Toskas A, Vaiopoulos G, Giannopoulou M, et al. Mucormycosis: ten-year experience at a tertiary-care center in Greece. Eur J Clin Microbiol Infect Dis. 2003;22(12):753-6.

Pagano L, Valentini CG, Posteraro B, Girmenia C, Ossi C, Pan A, et al. Zygomycosis in Italy: a survey of FIMUA-ECMM. J Chemother. 2009;21(3):322-9.

Lanternier F, Dannaoui E, Morizot G, Elie C, Garcia HD, Huerre M, Bitar D, et al. A global analysis of mucormycosis in France: the RetroZygo Study (2005-2007). Clin Infect Dis. 2012;54(1):35-43.

Chakrabarti A, Singh R. Mucormycosis in India: unique features. Mycoses. 2014;57(3):85-90.

Ferguson BJ. Mucormycosis of the nose and paranasal sinuses. Otolaryngol Clin North Am. 2000;33(2):349-65.

Greenberg RN, Scott LJ, Vaughn HH, Ribes JA. Zygomycosis (mucormycosis): emerging clinical importance and new treatments. Curr Opin Infect Dis. 2004;17(6):517-25.

Roden MM, Zaoutis TE, Buchanan WL, Knudsen T, Sakisova TA, Schaufele RL, et al. Epidemiology and outcome of zygomycosis: a review of 929 reported cases. Clin Infect Dis. 2005;41:634-653.

Connor BA, Anderson RJ, Smith JW. Mucor mediastinitis. Chest. 1979;75(4):525-6.

Helenglass G, Elliott JA, Lucie NP. An unusual presentation of opportunistic mucormycosis. Br Med J. 1981;282(6258):108-9.

Tedder M, Spratt JA, Anstadt MP, Hegde SS, Tedder SD, Lowe JE. Pulmonary mucormycosis: results of medical and surgical therapy. Ann Thorac Surg. 1994;57(4):1044-50.

Latif S, Saffarian N, Bellovich K, Provenzano R. Pulmonary mucormycosis in diabetic renal allograft recipients. Am J Kidney Dis. 1997;29(3):461-4.

Lee FY, Mossad SB, Adal KA. Pulmonary mucormycosis: the last 30 years. Arch Intern Med. 1999;159(12):1301-9.

Davoudi S, Graviss LS, Kontoyiannis DP. Healthcare-associated outbreaks due to Mucorales and other uncommon fungi. Eur J Clin Invest. 2015 Jul;45(7):767-73.

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(9462):876-8.

Warkentien T, Rodriguez C, Lloyd B, Wells J, Weintrob A, Dunne JR, et al. Invasive mold infections following combat-related injuries. Clin Infect Dis. 2012;55(11):1441-9.

Neblett FR, Benedict K, Bos J, Bennett SD, Lo YC, Adebanjo T, Etienne K, et al. Necrotizing cutaneous mucormycosis after a tornado in Joplin, Missouri, in 2011. N Engl J Med. 2012;367(23):2214-25.

Li DM, Lun LD. Mucor irregularis infection and lethal midline granuloma: a case report and review of published literature. Mycopathologia. 2012;174(5):429-39.

Bist SS, Varshney S, Bisht M, Gupta N, Bhatia R. Isolated palate ulcer due to mucormycosis. Indian J Otolaryngol Head Neck Surg. 2008;60(1):79-82.

Meis JF, Chakrabarti A. Changing epidemiology of an emerging infection: zygomycosis. Clin Microbiol Infect. 2009;15(5):10-4.

Sanofi National study. Screening India’s twin epidemic (SITE). Sanofi. 2011;1-5.

Chakrabarti A, Dhaliwal M. Epidemiology of mucormycosis in India. Current Fungal Infect Rep. 2013;7:287-92.

Kung VL, Chernock RD, Burnham CD. Diagnostic accuracy of fungal identification in histopathology and cytopathology specimens. Eur J Clin Microbiol Infect Dis. 2018;37(1):157-65.

Frater JL, Hall GS, Procop GW. Histologic features of zygomycosis: emphasis on perineural invasion and fungal morphology. Arch Pathol Lab Med. 2001;125(3):375-8.

Hoeppli RJC. Histological observations in experimental Schistosomiasis Japonica. Chin Med J. 1932;46:1179-86.

Splendore A. Sobre a cultura d’una nova especie de cogumello pathogenico. Revista de Sociedade Scientifica de Sao Paulo. 1908;62:62-3.

Cornely OA, Alastruey IA, Arenz D, Chen SCA, Dannaoui E, Hochhegger B, 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;19(12):405-21.

Therakathu J, Prabhu S, Irodi A, Sudhakar SV, Yadav VK, Rupa V. Imaging features of rhinocerebral mucormycosis: A study of 43 patients. The Egyptian J Radiol Nuclear Med. 2018;49 (2):447-52.

Mohanty A, Rohilla R, Meena S, Bora M, Singh A, Kaistha N, et al. Epidemiology of Mycotic Infections: Experience From A Tertiary Care Center Of Uttarakhand, India. Trop J Pathol Microbiol. 2021;7(3):93-8.

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(1):60-3.

Lanternier F, Poiree S, Elie C, Garcia HD, Bakouboula P, Sitbon K, et al. Prospective pilot study of high-dose (10 mg/kg/day) liposomal amphotericin B (L-AMB) for the initial treatment of mucormycosis. J Antimicrob Chemother. 2015;70(11):3116-23.

Pagano L, Offidani M, Fianchi L, Nosari A, Candoni A, Picardi M, et al. Infection Program. Mucormycosis in hematologic patients. Haematologica. 2004;89(2):207-14.

Nosari A, Oreste P, Montillo M, Carrafiello G, Draisci M, Muti G, et al. Mucormycosis in hematologic malignancies: an emerging fungal infection. Haematologica. 2000;85(10):1068-71.

Ibrahim AS, Gebremariam T, Husseiny MI, Stevens DA, Fu Y, Edwards JE, et al. Comparison of lipid amphotericin B preparations in treating murine zygomycosis. Antimicrob Agents Chemother. 2008;52(4):1573-6.

Larkin JA, Montero JA. Efficacy and safety of amphotericin B lipid complex for zygomycosis. Infect Med. 2003;20:201-6.

Singh A, Mohanty A, Jha S, Gupta P, Kaistha N. Concomitant Mucormycosis with Aspergillosis in Patients with Uncontrolled Diabetes Mellitus: A Case Series. J Clinical and Diagnostic Res. 2021;15(2):1-3.