Mucormycosis is a fungal infection caused by Mucorales fungi. It most commonly presents as rhino-orbito-cerebral mucormycosis and has increased in COVID-19 patients. Diagnosis involves microscopy, culture, biopsy and MRI showing characteristic findings. Treatment is with liposomal amphotericin B followed by oral antifungals like posaconazole. Early diagnosis and aggressive treatment by a multidisciplinary team is needed for optimal outcomes.

1. MUCORMYCOSIS: Diagnosis &Management
Dr.Aneesa Shahul.S
DM Fellow
AIIMS Jodhpur

2. Outline
 Introduction
 Pathogenesis and Clinical presentation
 Diagnosis
 Management
 prevention

3. Mucormycosis
 Potentially lethal, angioinvasive fungal infection
 predisposed by diabetes mellitus, corticosteroids and
immunosuppressive drugs, primary or secondary
immunodeficiency, iron overload.
 Increasing incidence of rhino-orbito-cerebral mucormycosis
(ROCM) in the setting of COVID-19 in India

4. Introduction contd..
 Rapidly progressive disease,
 Even a slight delay in the diagnosis or
appropriate management can have
devastating implications on patient survival
 Optimal outcome : early diagnosis prompted
by awareness of warning symptoms and signs
,high index of clinical suspicion, confirmation
of diagnosis by appropriate modalities, and
initiation of aggressive medical and surgical
treatment by a multidisciplinary team.

5. Microbiology

6. Mucorales
 These organisms are ubiquitous in nature and can be found
on decaying vegetation and in the soil.
 These fungi grow rapidly and release large numbers of spores
that can become airborne.
 The hyphae are broad (5 to 15 micron diameter), irregularly
branched, and have rare septations
 The lack of regular septations may contribute to the fragile
nature of the hyphae and the difficulty of growing the agents
of mucormycosis from clinical specimens

7. Risk factors
• Diabetes mellitus, particularly with ketoacidosis
• COVID-19
●Treatment with glucocorticoids
●Hematologic malignancies
●Hematopoietic cell transplantation
●Solid organ transplantation
●Treatment with deferoxamine
●Iron overload
●AIDS
●Injection drug use
●Trauma/burns
●Malnutrition

8. Pathogenesis
Rhizopus organisms have an enzyme, ketone
reductase, which allows them to thrive in high
glucose, acidic conditions.
Iron overload may predispose to mucormycosis
 Iron uptake by the fungus, stimulates fungal growth
and leads to tissue invasion

9. Why in Covid – 19 patients?
 1. Hyperglycemia due to uncontrolled pre-existing diabetes and high
prevalence rates of mucormycosis in India per se.
 2. Rampant overuse and irrational use of steroids in management of
Covid – 19.
 3. New onset diabetes due to steroid overuse or severe cases of Covid –
19 per se.
 4. Prolonged ICU stay and irrational use of broad spectrum antibiotics
 5. Pre-existing co-morbidities such as hematological malignancies, use
of immunosuppressants, solid organ transplant etc.
 6. Breakthrough infections in patients on Voriconazole (anti – fungal
drug) prophylaxis.
 Guideline for management of Mucormycosis in Covid – 19 patients ICMR May 2021

10. Rhino orbital cerebral
Pulmonary
Cutaneous
Renal
Gastrointestinal, DISSEMINATED

11. Red flag signs in ROCM
 Nasal stuffiness • Foul smell • Epistaxis • Nasal discharge - mucoid, purulent, blood-
tinged or black
 Nasal mucosal erythema, inflammation, purple or blue discoloration, white ulcer,
ischemia, or eschar
 Eyelid, periocular or facial edema • Eyelid, periocular, facial discoloration
 Regional pain – orbit, paranasal sinus or dental pain • Facial pain
 Worsening headache • Proptosis • Sudden loss of vision •
 Facial paresthesia, anesthesia • Sudden ptosis • Ocular motility restriction, diplopia •
Facial palsy
 Fever, altered sensorium, paralysis, focal seizure

12. APPROACH TO DIAGNOSIS

13. 1. Microscopy
2. Culture
3. Radiology
4.Biopsy
5. Molecular techniques

14. Microscopy
 Direct microscopy of the deep or endoscopy-guided nasal swab,
paranasal sinus, or orbital tissue, using a KOH mount and calcofluor
white.
 Non-septate or pauci-septate, irregular, ribbon-like hyphae; Wide-angle
of non-dichotomous branching (≥45-90 degree) and greater hyphal
diameter as compared to other filamentous fungi. These are 6-25 μm in
width.
 Stains: Hematoxylin-Eosin, periodic acid-Schiff, and Grocott-Gomori’s
methenamine-silver stains can also help in rapid diagnosis.
 90% sensitivity.

15. Mucor hyphae shows broad ribbonlike hyphae (arrows) that are 7–15 μm wide.
The hyphae lack regular septa and are pauciseptate.
The hyphae have irregular wide-angle branches

16. Culture
 Specimens: deep or endoscopyguided nasal swab, paranasal sinus, or
orbital tissue, bronchial wash, biopsy
 Media: Brain heart infusion agar, potato dextrose agar or preferably
Sabouraud dextrose agar with gentamicin or chloramphenicol and
polymyxin-B, but without cycloheximide
 Incubated at 30-37°C helps in genus and species identification and
antifungal susceptibility testing .
 Rapid growth of fluffy white, gray or brown cotton candy-like colonies. The
hyphae are coarse and dotted with brown or black sporangia.
 Only about 50% of samples from cases of probable ROCM grow the
organism on culture.

17. Molecular diagnostics
 Tissue sample (deep or endoscopy-guided nasal swab, paranasal
sinus, or orbital tissue), culture, or blood
 Molecular diagnostics have about 75% sensitivity and can be
used for confirmation of diagnosis where available
 There is promising role of quantitative polymerase chain
reaction.
 Matrix-assisted laser desorption ionization-time of flight
(MALDI-TOF) mass spectrometry can be used to identify the
causative species from culture specimens

18. Biopsy
 Histopathology with Hematoxylin Eosin, periodic acid-Schiff, and
Grocott-Gomori’s methenamine-silver special stain.
 Sample from the nasal mucosa, paranasal sinus mucosa and
debris or orbital tissue should be subjected to rapid diagnostic
techniques such as frozen section, and squash and imprint, and
also processed for routine fixed sections.
 Hyphae showing tissue invasion is confirmatory of invasive
ROCM.
 Histopathology provides diagnostic information in about 80% of
samples of probable ROCM.

19.  Both bronchoscopic and percutaneous lung biopsy are effective
tools to help diagnose PM.
 At histologic examination, one of the hallmarks of PM is hyphal
invasion of large and small blood vessels, resulting in
thrombosis and infarction
 Staining with phosphotungstic acid hematoxylin can show fine
threads of fibrin on the hyphal surfaces in blood vessels,
indicating thrombogenic activity

20. IMAGING
 Contrast-enhanced MRI is preferred over CT scan
 Nasal and paranasal sinus mucosal thickening with irregular patchy enhancement is an early sign.
 Ischemia and non-enhancement of turbinates manifests as an early sentinel sign on MRI – black turbinate
sign.
 The fluid level in the sinus and partial or complete sinus opacification signifies advanced involvement of
the paranasal sinuses.
 Thickening of the medial rectus is an early sign of orbital invasion.
 Patchy enhancement of the orbital fat, lesion in the area of the superior and inferior orbital fissure and the
orbital apex, and bone destruction at the paranasal sinus and orbit indicate advanced disease. Stretching of
the optic nerve and tenting of the posterior pole of the eyeball indicate severe inflammatory edema
secondary to tissue necrosis.

21.  MRI and MR angiography help determine the extent of
cavernous sinus involvement and ischemic damage to
the CNS.
The absence of paranasal sinus involvement has a
strong negative predictive value for ROCM.
 Comparative imaging over time helps monitor the
course of the disease.

22. Pulmonary mucormycosis
 Pulmonary mucormycosis is a rapidly progressive infection
that occurs after inhalation of spores into the bronchioles and
alveoli
 Pneumonia with infarction and necrosis results, and the
infection can spread to contiguous structures, such as the
mediastinum and heart or disseminate hematogenously to
other organ.
 Most patients have fever with hemoptysis that can sometimes
be massive
 Copious brown or blackish sputum, chest pain

23. Pulmonary Imaging
Chest X ray- Lobar and segmental consolidation
Unilateral can rapidly progress to multilobar and
bilateral disease
Bilateral- High Mortality
Multiple nodules/masses
Radiographics.rsna.org May 2020

25. CT Lungs
 In early PM, initial CT may show a perivascular ground-glass
lesion prior to the development of more extensive imaging
findings
 Ground-glass lesions usually progress to consolidation, nodules,
or masses
 Nodules and masses may have a ground-glass halo
 Presence of more than 10 lesions characteristic of PM

27. Imaging
 As fungus tends to invade the vasculature, necrosis is a common
feature
 Consolidation and masses may show a relative paucity of air
bronchograms at imaging.
 Other vascular findings that have been described include
pseudoaneurysm formation and abrupt termination of a
pulmonary artery branch, which appears with the vascular
cutoff sign.

28. Infection can spread to the pleura, chest wall,
mediastinum, diaphragm, and heart .
 Pleural thickening or effusion may indicate pleural
infection.
 Air in the intercostal space or subcutaneous soft
tissues usually indicates chest wall spread

30. Reverse halo sign
Ground-glass lesion with a peripheral rim of consolidation
 Reverse halo sign has been shown to be a specific sign of mucormycosis, occurring in
19%–94% of patients with PM
 One of the diagnostic challenges in patients suspected of having invasive fungal
pneumonia is differentiating aspergillosis from mucormycosis.
 The reverse halo sign can also help distinguish between other fungal pneumonias,
particularly IPA.

35. CLASSIFICATION

36. Possible- symptoms
Probable- DNE/MRI
Proven- Micro/HPE

37. Classes
 A patient who has symptoms and signs of ROCM in the clinical setting of concurrent or
recently treated (<6 weeks) COVID-19, diabetes mellitus, use of systemic corticosteroids
and tocilizumab, mechanical ventilation, or supplemental oxygen is considered as
Possible ROCM
 When the clinical symptoms and signs are supported by diagnostic nasal endoscopy
findings, or contrast-enhanced MRI or CT Scan, the patient is considered as Probable
ROCM
 Clinico-radiological features, coupled with microbiological confirmation on direct
microscopy or culture or histopathology with special stains or molecular diagnostics are
essential to categorize a patient as Proven ROCM.

38. STAGING OF ROCM

43. MANAGEMENT

44. Liposomal Amphotericin B in initial dose of 5mg/kg body weight is the treatment of
choice.
(10 mg/kg Is used in cases with CNS involvement)
Duration of therapy : till a favourable response is achieved and disease is stabilized
which may take several weeks
STEP DOWN to oral Posaconazole (300 mg delayed release tablets twice a day for 1 day
followed by 300 mg daily)
OR
Isavuconazole (200 mg 1 tablet 3 times daily for 2 days followed by 200 mg daily) can
be done.
ICMR May 2021

45. Mx contd….
 The therapy has to be continued until clinical resolution of signs and
symptoms of infection as well as resolution of radiological signs of active
disease and elimination of predisposing risk factors such as hyperglycemia,
immunosuppression.
 Conventional Amphotericin B (deoxy cholate) in the dose 1-1.5mg/kg may
be used if liposomal form is not available and renal functions and serum
electrolytes are within normal limits.

46. 1364 Indian Journal of Ophthalmology Volume 69 Issue 6
Figure 2: Management algorithm for Rhino-Orbito-Cerebral Mucormycosis (ROCM)

49. PREVENTIVE MEASURES

50. Judicious and supervised use of systemic corticosteroids in
compliance with the current preferred practice guidelines
Judicious and supervised use of tocilizumab in compliance
with the current preferred practice guidelines
Aggressive monitoring and control of diabetes mellitus
 Strict aseptic precautions while administering oxygen (sterile
water for the humidifier, daily change of the sterilized
humidifier and the tubes)
 Personal and environmental hygiene
 Betadine mouth gargle
 Barrier mask covering the nose and mouth

51. Timely initiation of Amphotericin B therapy
Keep high index of suspicion in presence of risk factors, daily
examination of eyes, nose and mouth for detecting signs
 Consider prophylactic oral Posaconazole in high-risk patients
(>3 weeks of mechanical ventilation, >3 weeks of supplemental
oxygen, >3 weeks of systemic corticosteroids, uncontrolled
diabetes mellitus with or without ketoacidosis, prior history of
chronic sinusitis, and co-morbidities with immunosuppression)

52. Summary
Aseptate broad hyphae with irregular branching
pattern
ROCM- Most common form
IOC- MRI and Biopsy
DOC- LAMB 5 mg/kg
Early diagnosis, aggressive multidisciplinary approach
and optimal therapy improves outcome
Judicious use of steroids and immunosuppressant
therapy