Mucormycosis is a rare but rapidly progressive fungal infection caused by fungi of the Mucorales order. It has seen increased incidence in India during the COVID-19 pandemic. It requires a high index of clinical suspicion for diagnosis. Risk factors include diabetes, immunosuppression, prolonged corticosteroid use, and voriconazole therapy. Early signs are non-healing ulcers and black eschar in the nasal or oral cavities. Diagnosis involves microscopy, culture and biopsy showing characteristic hyphae. Treatment involves antifungal therapy with amphotericin B and early surgical debridement of necrotic tissues. Strict prevention measures like use of sterile water in humidifiers are important

1. COVID 19 -ASSOCIATED
MUCORMYCOSIS
P R E S E N T E D B Y -
D R . R I C H A S I N G H
S E N I O R R E S I D E N T
D E E N D A Y A L U P A D H Y A Y A H O S P I T A L
N E W D E L H I , I N D I A
Dr. Richa Singh

2. Mucormycosis
Mucormycosis is an Acute invasive fungal disease
Rare but rapidly progressive disease process that can result in fatality within days. It is the most
lethal form of fungal disease with mortality rates of at least 50%.
Aspergillus and Zygomycetes (particularly Mucor and Rhizopus) are the causative fungi in most
cases .
A high degree of clinical suspicion is required in order to correctly and promptly diagnose and
manage this condition.
Since the onset of the COVID 19 pandemic there have been multiple reports across country
of very high incidence of mucormycosis among patients with COVID 19 .
Dr. Richa Singh

3. Aetiology
MUCOR MYCOSIS REFERS TO…… infection caused by fungi in order of Mucorales.
It is a unifying term for a group of Filamentous fungi in phyla MUCORALES that are capable of causing
rapidly progressive, fatal, opportunistic infections in humans.
Most common species are…Rhizopus oryza(m/c), Mucor
Others - Rhizomucor, Cunninghamella, Apophysomyces,
Saksenaea, Absidia and Syncephal astrum.
3RD most common angio-invasive Fungal Infection(after candidiasis and aspergillosis)
Dr. Richa Singh

4. Risk factors
Immunocompromised
state (HIV)
Haematological
malignancies and
patients who underwent
haematopeitic stem cell
transplant
Therapy- desferrioxime ,
radiation, antineoplastic
drugs , corticosteroids
Over the counter self
administration of high
dose steroids
Self/prolonged use of
broad spectrum-
antibiotics
Malnutrition
Post extensive burns and
trauma
Prematurity(neonatal
gastrointestinal
mucormycosis)
Dr. Richa Singh

5. High risk Covid
19 patients for
mucormycosis
Case of concurrent or recently(<6weeks) treated covid-19 esp
severe cases
Prolonged use of broad spectrum Antibiotics
High dose, prolonged or early initiation of steroids .
High level of IL-6 and serum Ferritin
History of use of Tocilizumab and other immunomodulators
Neutropenia ( decreased Absolute Neutrophil Count)
Uncontrolled Diabetes
Diabetes Ketoacidosis/ Metabolic acidosis
Dr. Richa Singh

6. Dr. Richa Singh

7. ?factors predisposing in post covid
illness -
?Use of Industrial
oxygen
?Increased Zinc
usage leading to
growth of fungus
?improper use of
humidifiers
?Depleted
adaptive immune
response post
covid 19
?Use of same
mask for
prolonged
duration
?Excessive steam
inhalation- altering
mucosa
?Voriconazole
prophylaxis
Dr. Richa Singh

8. ANGIOINVASION VESSEL THROMBOSIS TISSUE NECROSIS
Host Defence such as polymorphonuclear phagocytes kill Mucorales by the generation of
oxidative metabolites •Neutropenia, Hyperglycemia and acidosis are known to impair the ability
of phagocytes .
Patients treated with the iron chelator deferoxamine have a markedly increased incidence of
invasive mucormycosis • Rhizopus actually utilize deferoxamine as a siderophore to supply
previously unavailable iron to the fungus
 Patients in systemic acidosis have elevated levels of available serum iron, likely due to release
of iron from binding proteins in the presence of acidosis • Hence patients in diabetic ketoacidosis
are at high risk of developing rhinocerebral mucormycosis.
Inoculation occurs when spores reach the nasal cavity during inhalation. tiny spores then
become airborne and land on the oral and nasal mucosa of humans.
 Hematogenous spread to other organs can occur (lung, brain, and so on), as well
Dr. Richa Singh

9. Types
Dr. Richa Singh

10. Clinical Stages of
Rhinocerebral
mucormycosis
STAGE 1
Rhinomaxillary(Sinonasal
disease) - involves nose
and paransal sinuses.
STAGE 2 Rhino-orbital –
involves orbit ( superior
orbital fissure , orbital
apex syndrome)
STAGE 3 Rhino- orbito-
cerebral – Cerebral
involvement in which
intracranial spread
occurs.
Dr. Richa Singh

11. WHEN AND HOW TO SUSPECT CAM?
Patients with Covid-19 illness (active/recovering/post-discharge) – common
presentation: rhino-orbito-cerebral mucormycosis (ROCM)
Dr. Richa Singh

12. Symptoms
RHINOSINUSITIS / RHINOMAXILLARY:
Headache(early)
Hemifacial pain (early)
Nose block, crusting (early)
Unilateral face swelling , loss of cheek
sensation
Nasal discharge
Epistaxis
Fever- recurrence
Loss of teeth
RHINO-ORBITAL:
Diplopia
Blurring of vision
Vision loss
Retro-orbital pain
RHINO-ORBITO-CEREBRAL:
Altered sensorium
Cranial nerve palsy
Hemiplegia
Dr. Richa Singh

13. SIGNS
NOSE-
Crusting
Nasal discharge with pus
Blackened middle turbinate
Devascularised/ devitalised mucosa, with excessive
erosion
“necrotic eschar/ulcer” anywhere in mucosa of
nose, palate
Cutaneous:
Black necrotic eschar, ulcers
Perinasal, infraorbital or u/l face cellulitis
Loss of cheek sensation.
CEREBRAL:
Altered sensorium
Seizures
Hemiplegia
Cranial nerve palsies
EYES:
Ptosis
Chemosis
Proptosis
Periorbital edema
Ophthalmoplegia
Loss of visual acquity
ORAL CAVITY:
Palatal discloloration
Palatal ulcers , necrotic
eschar
Loosening of tooth
Oroantral fistula
Dr. Richa Singh

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15. Evaluation of mucor patient
 Multidisciplinary approach is required with infectious disease specialist,
microbiologist, histopathologist, intensivist, neurologist, ENT specialist,
ophthalmologist, dentist, surgeons, radiologists etc.
 Detailed history
 ENT, ophthalmic and neurological examination to assess the extent of disease.
 Complete blood counts, blood urea, s. creatinine, bl. Glucose, arterial blood gas(ABG) analysis
 Blood tests – HbA1c , random blood sugar levels, serum electrolytes, urine ketones ,serology(HIV,
HBsAg, HCV), CRP, SERUM FERRITIN , ESR
Dr. Richa Singh

16. Diagnosis
Examination of oral cavity:
-palatal ulcer, exposed necrotic bone, oro-antral
fistula , loose tooth, pale ischemia, movable jaw
-pain , tenderness over palate,
discoloration(brownish) (seen early)
-*palate involvement* is seen very early in post
covid mucormycosis
**if done early can have normal mucosa.
DNE and ENT examination is advised to be
repeated, 48 hourly in a suspected/symptomatic
patient FOLLOWED by radiological investigation
for earliest detection of mucormycosis .
Diagnostic (rigid) nasal endoscopy(DNE)
-*pale mucosa, crusting, “blackened” middle
turbinate , pus discharge, necrosed/devitalised
mucosa, echars
--biopsy taken from Middle turbinate(m/c site)
and from echars, ulcers , or devitalised tissue for
Histopathological examination.
Swabs- deep scraping pus swabs taken for
culture and microscopy.
Urgent fungal smear
Dr. Richa Singh

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19. Direct microscopy – optical brighteners like
Blankophor and Calcofluor White Hyphae
are of variable width, non septate, irregular
ribbon like with wide angle bifurcations (90˚)
Periodic acid-Schiff or Grocott Gomori’s
methenamine silver staining - highlight fungal
hyphae
Rapid growth (3 to 7 days) on Sabouraud agar
and potato dextrose agar incubated at 25◦C to
30◦C
Aggressive vertical growth toward the lid of
the Petri dish – Lid lifters
Histopathology:
Hyphae will be seen
Neutrophilic or granulomatous inflammation
Invasive disease is characterized by
prominent infarcts and angioinvasion.
Perineural invasion may be present.
 Angioinvasion - extensive in neutropenic
patients
Antigen Detection & Specific T cells
Galactomannan and ß-D Glucan – If
negative likely invasive mucormycosis.
 Mucorales-specific T cells - enzyme-
linked immunospot (ELISpot) assay.
Dr. Richa Singh

20. Radiology
* Rhinosinusitis/ Rhinomaxillary disease or disease
involving only nose and paranasal sinus –
CT SCAN NOSE AND PNS(non-contrast) is advised
* Rhino-orbital and Rhino-orbital-cerebral- MRI T2W
BRAIN/ORBIT/FACE with fat suppression AND gadolinium
enhanced imaging is advised .
High specificity –
Nasal soft tissue/septal/turbinate ulceration and necrosis
Periantral fat stranding – retroantral and peri-maxillary
Bone dehiscence(maxilla/oroantral fistula)
Orbit invasion-erosion of lamina papyracea and/or
infraorbital rim
Pterygopalatine fossa extension(obliteration of Fat)
Nasolacrimal duct erosion and lacrimal sac
involvement(watering of eye, chemosis)
Dr. Richa Singh

21. Characteristically - * BLACK TURBINATE SIGN/ BLACK MUCOSA SIGN*
Suggesting devitalised sino-nasal mucosa by mycotic vascular invasion.
Nature of secretions – watery>> fungal sludge / devitalised soft tissue / necrosed
CT will show hyper – deposition of calcium,manganese and zinc salts
Earliest CT finding – soft tissue widening , soft tissue windowing – perimaxillary, retroantral and perisinus space, fat
stranding and middle turbinate necrosis.
Earliest MRI – decreased vascularisation(u/l), black turbinate sign , breaking of mucosal lining,
Early changes in cerebrum included leptomeningeal enhancement(abscess/granuloma), evidence of cerebral infarct
Dr. Richa Singh

22. MRI STIR IMAGE
NON CONTRAST CT SCAN
Dr. Richa Singh

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25. GLOBAL GUIDELINE FOR THE DIAGNOSIS AND MANAGEMENT
OF MUCORMYCOSIS
European Confederation of Medical Mycology
Mycoses Study Group Education and Research Consortium
Dr. Richa Singh
Published in lancet in November 2019.

26. Dr. Richa Singh

27. FIRST-LINE ANTIFUNGAL MONOTHERAPY
LIPOSOMAL AMPHOTERICIN B : 5 MG/KG PER DAY TO 10 MG/KG PER DAY
AMPHOTERICIN B DEOXYCHOLATE IS EFFECTIVE, BUT ITS USE IS LIMITED BY ITS
SUBSTANTIAL TOXICITY. USE SHOULD BE RESTRICTED.
Dr. Richa Singh

28. OTHER ANTI FUNGALS
Posaconazole
broad-spectrum oral antifungal available Dose- 800 mg/day divided in 4
Isavuconazole
Another triazole Available in oral and intravenous formulations Administered with a loading dose of 200 mg 3 times a day for 2
days and 200 mg daily thereafter
Fluconazole, voriconazole, and itraconazole do not have reliable activity against mucormycosis
Novel regimens for the treatment of mucormycosis include a combination of lipid-based amphotericin plus either an
posaconazole or Isavuconazole
Dr. Richa Singh

29. SURGICAL DEBRIDEMENT
Revision of surgical exploration of the sinuses and orbit is required to
ensure that all necrotic tissue has been debrided and the infection has not
progressed
Blood vessel thrombosis , resulting in tissue necrosis during mucormycosis
can result in poor penetration of antifungal agents to the site of infection.
 Therefore, debridement of necrotic tissues may be important for
complete eradication of mucormycosis.
 Patients who did not undergo surgical debridement of mucormycosis had
a far higher mortality rate than patients who underwent surgery
Dr. Richa Singh

30. Early
surgical
debridemen
t (all
patients)
Transcutaneo
us retrobulbar
Amphotericin
B (TRAMB) 1
ml
of 3.5
mg/ml
(select
cases only)
Orbital
Exenteration
(patients
with
extensive
orbital
involvement)
• Endoscopic sinus surgery
debridement
• (good prognosis)
Nasal and sinus
involvement is present
without bony erosion of
maxilla/ zygoma and orbital
floor
• Maxillectomy(partial/
total)
Maxilla
involvement
• Maxillectomy(partial/ total) with
• Zygoma
debridement
Maxilla + Minimal
zygoma
involvement
•Maxillectomy(partial/ total),Zygoma
debridement
•Debridement of Orbital floor/ walls,Localised
debridement of necrosed tissue in early
localised orbital disease
Maxilla+ Zygoma+
orbit
• 1) Vision loss 2) Total ophthalmoplegia 3) Chemosis 4) Necrosis of
orbital tissues
• NOTE:- Loss of vision in not always the indicationof exenteration
Exenteration of eye
in case of
• Anterior table:- Debridement
• Posterior table:- Cranialization
• Debridement of Osteomyelitic skull bone and
involvement of the cerebral parenchyma (Safe
maximum resection)
Frontal bone and
skull base
@Multidisciplinary Mucor management team_Version
1.0_16.05.2021 (AIIMS Rishikesh)
Dr. Richa Singh

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32. Adjuvant
treatment if
available-
HYPERBARIC OXYGEN THRAPY
Exerts a fungistatic effect
 aid in neovascularization
Dose-
exposure to 100% oxygen for 1and ½- 2 hours at pressures
from 2- 2.5 atm with 1 or 2 exposures daily for a total of 40
treatments.
Immune-augmentation strategies such as
Administration of granulocyte (macrophage)
 colony-stimulating factor or interferon-g alone or in
combination with granulocyte transfusions have shown
promise in vitro and in case reports
Dr. Richa Singh

33. SOP for strict adherence of
humidifiers
 Always use distilled or sterile water
 Never use un-boiled tap water nor mineral water
 Fill up to about 10 mm below the maximum fill line
 Do not let the water level pass below the maximum fill line
 Water level should be checked twice daily and topped up when required
 Water in the humidifier should be changed daily
 Humidifier should be washed in mild soapy water, rinsed with clean water and dried in air
before reuse
 Once a week (for the same patient) and in between patients, all the components of the
humidifier should be soaked in mild antiseptic solution for 30 minutes, rinsed with clean
water and dried in air.
Dr. Richa Singh

34. DOs
Control
hyperglycemia
1
Monitor blood
glucose level post
COVID- 19 discharge
and also in diabetics
2
Use steroid
judiciously- correct
timing, correct dose
and duration
3
Use clean, sterile
water for humidifiers
during oxygen
therapy
4
Use antibiotics/
antifungals
judiciously
5
Dr. Richa Singh

35. DONTs
Do not miss signs and symptoms
Do not miss
Do not consider all the cases with blocked nose as cases of bacterial sinusitis, particularly in the
context of immunosuppression and/or COVID-19 patients on immunomodulators
Do not consider
Do not hesitate to seek aggressive investigations, as appropriate (KOH staining & microscopy,
culture, tissue biopsy), for detecting fungal etiology
Do not hesitate
Do not lose crucial time to initiate treatment for mucormycosis
Do not lose
Dr. Richa Singh

36. Why early intervention is necessary?
High mortality rate Poor prognosis Progresses rapidly
Results in carotid
artery occlusion or
cavernous sinus
thrombosis
Permanent residual
effects of the
disease occur up to
70% of the time

37. CONCLUSION
 Mucormycosis is a fatal infection
 Early recognition will prevent further dissemination of disease
Medical as well as surgical management plays equal role in its treatment
 The detection and limitation of underlying cause is necessary
Overcoming all the medical and surgical difficulties and making the patient disease free is a
challenging task
Dr. Richa Singh

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