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 Table of Contents  
Year : 2019  |  Volume : 21  |  Issue : 1  |  Page : 47-49

Mixed opportunistic infection with Mucor, Aspergillus and Candida in oculo-rhino-cerebral mycosis: An uncommon case

1 Department of Clinical Microbiology and Pathology, Northern Railway Central Hospital, New Delhi, India
2 Department of ENT, Northern Railway Central Hospital, New Delhi, India

Date of Web Publication12-Aug-2019

Correspondence Address:
Dr. Meenakshi Agarwal
Department of Clinical Microbiology and Pathology, Northern Railway Central Hospital, Connaught Place, New Delhi - 110 001
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jacm.jacm_2_19

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Mucormycosis is a life-threatening invasive fungal infection usually occurring in immunocompromised patients or in patients with uncontrolled diabetes mellitus. It carries a high mortality rate. Aspergillosis which is caused by Aspergillus species may cause an invasive disease in immunosuppressed patients. A 63-year-old female patient with type 2 diabetes mellitus presented with sudden onset painless diminution of vision in the right eye and restriction of orbital movements. Oculo-rhino-cerebral mucormycosis was diagnosed on contrast-enhanced computed tomography scan. Histopathology and fungal culture showed mixed infection with Mucor, Aspergillus and Candida. Liposomal Amphotericin B was started and surgical debridement was done.

Keywords: Aspergillus, Candida, mixed, Mucor, oculo-rhino-cerebral mycosis

How to cite this article:
Pandey D, Agarwal M, Chadha S, Aggarwal D. Mixed opportunistic infection with Mucor, Aspergillus and Candida in oculo-rhino-cerebral mycosis: An uncommon case. J Acad Clin Microbiol 2019;21:47-9

How to cite this URL:
Pandey D, Agarwal M, Chadha S, Aggarwal D. Mixed opportunistic infection with Mucor, Aspergillus and Candida in oculo-rhino-cerebral mycosis: An uncommon case. J Acad Clin Microbiol [serial online] 2019 [cited 2022 Sep 26];21:47-9. Available from: https://www.jacmjournal.org/text.asp?2019/21/1/47/264248

  Introduction Top

Opportunistic fungal infections can be life-threatening, in the presence of immunosuppression or uncontrolled diabetes mellitus, due to their invasive potential. Mucormycosis of oculo-rhino-cerebral region is an uncommon rapidly spreading invasive fungal infection and is life-threatening with a mortality rate nearing 50%.[1] Its coexistence with Aspergillus and Candida makes it more uncommon.

  Case Report Top

A 63-year-old diabetic and hypertensive female patient disoriented to time, place and person presented in emergency with sudden onset painless diminution of vision and proptosis of the right eye, with restriction of orbital movements for one month. She was referred from a secondary healthcare centre with diagnosis of 'orbital cellulitis with right side pansinusitis'. Her Random blood sugar (RBS) was 208 mg/dl and HbA1C was 11.10% at the time of admission. Nasal examination showed extensive nasal crusts, septal perforation and black eschar in bilateral nasal cavities. Eye examination revealed swollen right eye, periorbital swelling, pupil non-reactive and absent extraocular movements in all directions with ptosis and slight proptosis. Magnetic resonance imaging (MRI) orbit revealed orbital cellulitis, spiral contrast-enhanced computed tomography paranasal sinuses (PNS) and MRI brain showed heterogeneously enhancing contents in the PNS (especially right frontal and bilateral ethmoid) with extension into the right orbit with pre-septal cellulitis with intracranial spread. Right cavernous sinus thrombosis with thrombosis of the superior ophthalmic vein and thrombosis of the right internal carotid artery (ICA) were noted; the findings were suggestive of rhino-oculo-cerebral mucormycosis [Figure 1]. Nasal tissue was sent for direct KOH, histopathological examination and fungal culture. Direct KOH wet mount of the nasal tissue showed budding yeast cells and few distorted right angle branching thick, hyaline aseptate hyphae. Histopathological examination showed exudate with intermixed non-septate broad fungal hyphae, conidiophores, budding yeast cells, underlying fibroconnective tissue and necrosis. Fungal culture was done on Sabouraud dextrose agar and showed a mixture of cottony growth and creamy pasty growth. Lactophenol cotton blue (LPCB) mount of the culture showed budding yeast cells (germ tube negative) identified as non-albicans Candida spp., broad aseptate hyphae with sporangiophores and identified as Mucor spp. and septate hyphae with conidiophores with single uniseriate phialide which covered the upper half of the vesicle and were parallel to the axis of stalk were identified as Aspergillus fumigatus. The patient was started on insulin and other supportive treatments in the form of broad-spectrum antibiotics and adequate hydration. Liposomal Amphotericin B was started in a dose of 100 mg/day, and the dose was increased up to 200 mg/day over the next one week with regular monitoring of blood parameters to monitor for toxicity of Amphotericin B. The treatment included intravenous (IV) antibiotics Augmentin 1.2 g BD for 20 days, followed by IV Ceftriaxone 1 g BD for 10 days, IV, antifungal liposomal Amphotericin B 150–200 mg/day in five per cent dextrose six days a week (total cumulative dose given was 8 g). Surgical debridement of the affected sinonasal fungal and necrotic tissue with orbital decompression was done. However, orbital exenteration was also planned but could not be done as the patient did not give consent for the same. After polyfungal infection was confirmed on histopathology and culture, Voriconazole was also added to the treatment regimen by the clinician. The duration of hospital stay was almost two months, and in our hospital, treatment is free of cost.
Figure 1: (a and b) Spiral contrast-enhanced computed tomography paranasal sinuses, (c and d) magnetic resonance imaging brain: Arrow Showing heterogeneously enhancing contents in the paranasal sinuses with extension into right orbit with intracranial spread

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  Discussion Top

India is the most affected country by mucormycosis, contributing about 44.3% of the entire cases reported worldwide.[2] Mucormycosis of the rhino-oculo-cerebral region is an invasive fungal infection with life-threatening potential. In immunocompromised individuals including diabetics, invasive fungal sinusitis can be dangerous due to insidious onset, rapid intracranial spread and tissue destruction.[3]

Fungal opportunistic infections are commonly seen in immunocompromised individuals. This was a unique case because clinicians suspected it to be a case of mucormycosis alone in a patient with uncontrolled diabetes mellitus, but microbiological and histopathological investigations revealed a mixed infection with Mucor, Aspergillus and Candida. All these three fungi are well known to cause opportunistic infections in immunocompromised hosts.

Mucormycetes, the group of fungi that cause mucormycosis, are present throughout the environment, particularly in soil and in association with decaying organic matter. They belong to order Mucorales and include Rhizopus species (causes majority of cases)[4] Mucor, Cunninghamella bertholletiae, Apophysomyces, Lichtheimia (formerly Absidia), Saksenaea and Rhizomucor.

Common predisposing factors for mucormycosis are diabetes mellitus, allogeneic stem cell transplant recipients and haematological malignancies undergoing chemotherapy in the developed world.[5] In developing country like ours, it has sporadic occurrence mainly in patients with uncontrolled diabetes and trauma.[6],[7],[8] Most commonly, it spreads from the nasal mucosa to the turbinate bones, PNS, orbit and palate with extension into the brain where massive invasion of the cavernous sinuses and major blood vessels cause major infarct; thus, it is also labelled as one of the emerging angioinvasive diseases.

Invasive aspergillosis of the sino-orbital area may mimic mucormycosis and malignant neoplasia[9] due to the presence of facial mass and slowly progressive proptosis and local tissue destruction. When it becomes angioinvasive, it can be rapidly destructive and often fatal if not treated in time.[10] Invasive aspergillosis of the rhino-oculo-cerebral region appears as yellow or black necrotic areas spreading to the adjoining regions.[11] With the emergence of debilitating immune states and metabolic disorders such as diabetes, infection with more than one fungus is also being witnessed. We also isolated non-albicans Candida from this specimen. Candida is a well-known pathogen to cause invasive fungal rhinosinusitis in diabetics. In this case, direct wet mount, histopathology and culture showed the presence of budding yeast cells in the clinical specimen. Concomitant mucormycosis with aspergillosis along with non-albicans Candida spp. is an uncommon finding. We have not seen similar case in a five-year span, although we are getting three to four cases of isolated mucormycosis in the sinonasal region. Few case reports of combined mucormycosis and aspergillosis of the rhinocerebral region in a diabetic patient have been reported by Nagarkar et al., Rit et al. and Alfano et al., whereas Maiorano et al. presented such a case in a patient with Castleman disease and Goswami et al. reported it in a renal transplant patient.[10],[12],[13],[14],[15] We found a single case report of mixed infection with Mucor, Aspergillus and Candida which was reported from traumatic wound in the hand.[16]

Thus, more than one fungus can be isolated in patients with invasive fungal rhinosinusitis. A high index of suspicion should be kept in mind in diabetics of mixed infection with Candida, Aspergillus and zygomycetes in case of rhinocerebral mycosis. Histopathology and mycology culture will help clinicians in choosing the best possible line of treatment in oculo-rhino-cerebral mycosis. Mixed fungal infection will require more aggressive and focussed line of treatment as compared to infection with a single fungal agent.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

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Conflicts of interest

There are no conflicts of interest.

  References Top

Cruickshank G, Vincent RD, Cherrick HM, Derby K. Rhinocerebral mucormycosis. J Am Dent Assoc 1977;95:1164-8.  Back to cited text no. 1
Mignogna MD, Fortuna G, Leuci S, Adamo D, Ruoppo E, Siano M, et al. Mucormycosis in immunocompetent patients: A case-series of patients with maxillary sinus involvement and a critical review of the literature. Int J Infect Dis 2011;15:e533-40.  Back to cited text no. 2
Swarajyalakshmi M, Jyothilakshmi G. Candida kefyr in invasive paranasal sinusitis. Indian J Otolaryngol Head Neck Surg 2014;66:371-4.  Back to cited text no. 3
Rippon J. Medical Mycology. Philadelphia, PA: WB Saunders; 982. p. 615-37.  Back to cited text no. 4
Spellberg B, Edwards J Jr., Ibrahim A. Novel perspectives on mucormycosis: Pathophysiology, presentation, and management. Clin Microbiol Rev 2005;18:556-69.  Back to cited text no. 5
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.  Back to cited text no. 6
Prabhu RM, Patel R. Mucormycosis and entomophthoramycosis: A review of the clinical manifestations, diagnosis and treatment. Clin Microbiol Infect 2004;10 Suppl 1:31-47.  Back to cited text no. 7
Chakrabarti A, Das A, Mandal J, Shivaprakash MR, George VK, Tarai B, et al. The rising trend of invasive zygomycosis in patients with uncontrolled diabetes mellitus. Med Mycol 2006;44:335-42.  Back to cited text no. 8
Sivak-Callcott JA, Livesley N, Nugent RA, Rasmussen SL, Saeed P, Rootman J. Localised invasive sino-orbital aspergillosis: Characteristic features. Br J Ophthalmol 2004;88:681-7.  Back to cited text no. 9
Rit K, Saha R, Dey R, Barik G. Rhino-oculo-cerebral Aspergillus and mucor co-infections in an immunocompromised patient with type 2 diabetes mellitus. Med J DY Patil Univ 2014;7:486-8.  Back to cited text no. 10
  [Full text]  
Romett JL, Newman RK. Aspergillosis of the nose and paranasal sinuses. Laryngoscope 1982;92:764-6.  Back to cited text no. 11
Nagarkar NM, Verma H, Punia R. Co-existing mucormycosis with aspergillosis in a patient with diabetes mellitus- first case report. Online J Otolaryngol 2014; 4:257-64.  Back to cited text no. 12
Maiorano E, Favia G, Capodiferro S, Montagna MT, Lo Muzio L. Combined mucormycosis and aspergillosis of the oro-sinonasal region in a patient affected by Castleman disease. Virchows Arch 2005;446:28-33.  Back to cited text no. 13
Alfano C, Chiummariello S, Dessy LA, Bistoni G, Scuderi N. Combined mucormycosis and aspergillosis of the rhinocerebral region.In Vivo 2006;20:311-5.  Back to cited text no. 14
Goswami S, Vohra R, Raju BM, Agarwal A. Concomitant Mucormycosis and Aspergillosis of Rhinocerebral Region in a Renal Transplant Patient – Air Cooler Being the Culprit. Indian Journal of Medical Case Reports 2016:5;30-4. Available from: http://www.cibtech.org/jcr. [Last accessed on 2019 May 29].  Back to cited text no. 15
Obradovic-Tomasev M, Popovic A, Vuckovic N, Jovanovic M. Mixed fungal infection (Aspergillus, Mucor, and Candida) of severe hand injury. Case Rep Infect Dis 2014;2014:954186.  Back to cited text no. 16


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