mucormycosis in the covid era in India. it is mostly seen in the post-recovery patient of covid - 19. most of the data are derived from the 2nd wave of covid in India.

1. Mucormycosis
By Dr. Bomkar bam

2. Introduction
©drseshasai
• Mucormycosis (formerly Zygomycosis) – It is an acute,
granulomatous and oppurtunistic infection that occurs mostly in
immunocompromised patient.
• Ubiquitous in soil and forms Sporangiospores.
• It is commonly known as “black fungus” due to its black colour
formation in the affected area.
• Recently it is more commonly seen after covid recovery patient.
• Mortality rate of those affected patient is way more dangerous than
covid patient.

3. Species
 Most common species are
1. rhizopus sp.
2. Mucor sp.
3. Rhizomucor sp.

4. Rhizopus sp
Mucor species

5. EPIDEMIOLOGY
 internationaly 1% patients with low
immunity.
 mucor mycosis carries a very high
mortality (50%-85%).
 no racial factors predispose.
 sex is not likely to affect.

6. MAJOR ROUTE OF
INFECTION
 INHALATION OF SPORES.
 INGESTION.
 TRAUMATIC INOCULATION.

7.  Agents of mucormycosis are ubiquitous and frequently
airborne.
 Infections mainly involves the lungs, sinuses and the brain
 Pathogenesis involves invasion of major blood vessels, with
consequent ischemia, necrosis, and infarction of
contiguous tissues
 Neutrophils play a central role in the defence of the host
against mucormycosis
 Ketoacidosis, hyperglycaemia, and hypoxia are excellent
growth conditions for these fungi
 Ketoacidosis decreases inflammatory responses and delays
local aggregation of granulocytes and fibroblasts
PATHOGENESIS

8. Types
©drseshasai
1. Rhino-cerebral – most common
2. Pulmonary
3. Disseminated – most deadly
4. Cutaneous/Soft tissue
5. Gastro Intestinal

9. Risk factors - major risk factors
 Uncontrolled diabetes mellitus in ketoacidosis 80-90%
of rhinocerebral mucormycosis
 Deferoxamine therapy
 Iron and aluminium overload
 Burns (major)
 Voriconazole therapy
 Severe trauma (tornados, tsunamis, war)
 Protein energy malnutrition

10. Risk factors - other risk factors
 Other forms of metabolic acidosis
 Treatment with immunosuppressive drugs
(corticosteroids, anti-neoplastics)
 Organ or bone marrow transplantation
 Neutropenia
 MalignanciesIV drug abuse
 HIV/AIDS
 Chronic kidney disease
 Liver cirrhosis and hepatic failure

11. RELATIONSHIP BETWEEN
PREDISPOSING FACTORS AND
SITE OF INFECTION
 diabetic ketoacidisis (DKA)- rhinocerebral.
 neutropenia- pulmonary & disseminated.
 steroids-
pulmonary,rhinocerebral,disseminated.
 malnutrion- GI tract
 trauma,catheter,skin maceration-
cutaneous/ subcutaneous
 deferoxamine-disseminated

12. 1. RHINOCEREBRAL MUCORMYCOSIS
 50% of cases occur in patients with DM.
 50%CASES OF TOTAL CASES OF MUCOR
MYCOSIS.
 Usually occurs during an episode of DKA , with
disruption of host defense mechanisms thereby
permitting growth of Rhizopus oryzae. Such growth
is inhibited by correction of acidosis.

13. Clinical features
 Onset with nasal stuffiness
,epistaxis and facial pain.
 Later ,proptosis ,
visual loss
,chemosis and
ophthalmoplegia.
 Fever and confusion.
 Black necrotic eschar on the
nasal turbinates or palate :
very characteristic

14. Complications
 Cavernous sinusthrombosis.
 Multiple cranial nervepalsies.
 Visualloss.
 Frontal lobeabscess.
 Carotid artery or jugular vein thrombosis
causinghemiparesis.

15.  Punchbiopsy (GOLD STANDARD) of the
lesion followed by fungal stains andculture.
 Histological examination reveals the
characteristic broad , branching hyphae of
Rhizopus invading thetissue.
 CTor MRIof the head reveal air-fluid level in
the sinusesand involvement of deep tissues
Diagnosis

16. RHINOCEREBRAL MUCORMYCOSIS

17. CT PNS – bony erosion of palate, septum and
maxilla.

18. 2. PULMONARY MUCORMYCOSIS
 Seen most commonly in- neutropenia,pateints
on chemotherpy,leukemia.
 Dysponea ,cough& chest pain &fever
 Radiologicaly- consolidation,isolated
masses,cavitaion,wedge shaped infarcts.
 Ct scan best method to detect the extent.

19. REVERSE HALO SIGN
Focal area of Ground Glass Opacity
surrounded by ring of consolidation

20. 3. CUTANEOUS MUCORMYCOSIS
 Trauma is the predisposing factor.
 Invasive locally .
 May lead to necrotizing fascites - Mortality
upto 80%.
 Surgical debridement.

21. 4. GASTROINTESTINAL MUCORMYCOSIS
 Rare, occurs in extremaly
malnourished, children.
 Stomach,colon & ileum are most commonly
involved.
 Abdominal pain, nausea, vomiting, May
present as intra abdominal abscess, or
perforation of the viscus. Needs biopsy.
 Prognosis very poor

22. General approach to Diagnosis
©drseshasai
Microscopy
Direct microscopy in 10-20 % KOH
– 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

23. ©drseshasai
Culture
Tissue swabs, sputum, or BALcultures are usually nondiagnostic
Direct microscopy of bronchoalveolar lavage & transbronchial
biopsy may increase the yield
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

24. Diagnosis-Radiology
©drseshasai
• Plain x-ray
• CT scan- Infiltrate, wedge-shaped consolidation, multiple
nodules (>10) , cavitation, mycetoma, lobar collapse, Halo
sign & Air Crescent sign , Reverse Halo Sign
• MRI scan

25. Diagnosis
©drseshasai
Histopathology
Hyphae will be seen
Neutrophilic or granulomatous inflammation
Absent in a few cases - immunosuppressed patients.
Invasive disease is characterized by prominent infarcts and
angioinvasion.
Perineural invasion may be present.
Angioinvasion - extensive in neutropenic patients

26. Diagnosis
©drseshasai
Molecular based methods
PCR, RFLP, DNA sequencing that targets the 18S
ribosomal DNA of Mucorales
Antigen Detection & Specific Tcells
Galactomannan and ß-D Glucan – If negative likely invasive
mucormycosis
Mucorales-specific Tcells - enzyme-linked immunospot
(ELISpot) assay Recommendation

27. Treatment
©drseshasai
General principles
Early diagnosis
Early administration of active antifungal agents
Reversal of underlying factors
Complete removal of all infected tissues
Use of various adjunctive therapies

28. ©drseshasai
PRIMARY ANTIFUNGAL THERAPY
Liposomal Amphotericin-B first line recommended
agent
Fluconazole, Voriconazole,
Itraconazole –Absidia species
Posaconazole, Isuvaconazole can also be used as
first line therapy

29. Liposomal Amphotericin B
Can be given as 5mg/kg/day to 10mg/kg/day for
4-6 weeks
Surgery + Lip Amp Bincreases survival rates and
cure rates
Monitoring of kidney function every 3rd day
Blood pH, electrolyte and CBC.

30. Posaconazole 800mg/day in 2 or 4 divided doses
– first line, Salvage therapy
Isuvaconazole – 200mg OD. But VITAL study
showed higher mortality rates and poor
response
Azoles

31. ©drseshasai
Duration of Treatment
Highly individualized
Near normalization of radiograph, negative
biopsy specimens and cultures, recovery from
immunosuppression

32. Treatment - Surgery
©drseshasai
• Removal of necrotic tissue – Increases
penetration of antifungals
• Lobectomy, Pneumonectomy or wedge
resection Surrounding infected healthy-looking
tissues should be removed
• Groll A et al. – Mortality reduced by 79%

33. Treatment - SalvageTherapy
If disease is refractory or intolerance
towards previous antifungal therapy.
Posaconazole(A)
Polyenes + Posaconazole(B)
Lipid complex, liposomal, Colloidal
dispersion (B)
Polyenes + Caspofungin(C)

34. Treatment – Adjunctive
©drseshasai
Hyperbaric Oxygen – 100% O2 at 2atm pressure for 90
min twice a day (C)
Cytokine therapy in hematological malignancy –
Granulocyte transfusion +/- IFNγ (C)
Lovastatin
VT-1161(otesaconazole) – Inhibits fungal CYP51
Nivolumumab and IFNγ

35. Treatment – Adjunctive
©drseshasai
Deferasirox-AmBisome Therapy for Mucormycosis (DEFEATMucor)
study
First randomized trial for any treatment of mucormycosis
45%(5) mortality at 30 days, 82%(9) mortality at 90 days
Deferasirox (iron chelator) cannot be recommended as
part of an initial combination regimen for the treatment
of mucormycosis.

36. How to prevent
 Use mask if you are visiting dusty construction sites
 Wear shoes, long trousers, long sleeve shirts and
gloves while handling soil (gardening), moss and
manure.
 Personal hygiene.

37. When to suspect
 Sinusitis – nasal blockage or congetion, nasal
discharge (blackish/bloody), local pain on cheek bone
 One side facial pain, numbness or swelling
 Blackish discolouration over bridge of nose/palate
 Tooth ache, loosening of teeth, jaw involvement
 blurred or double vision with pain, fever, skin lesion,
necrosis
 Chest pain, hemoptysis, respiratory depression

38. Do’s
 Control hyperglycemia
 Monitor blood glucose level post COVID-
19 discharge and also in diabetics
 Use steroid judiciously – correct timing,
correct dose and duration
 Use clean, sterile water for humidifiers
during oxygen therapy
 Use antibiotics/antifungals judiciously

39. Don’ts
 Do not miss warning signs and symptoms
 Do not consider all the cases with blocked
nose as cases of bacterial sinusitis,
particularly in the context of immunosuppression
and COVID -19 patient on immunodulators
 Do not hesitate to seek aggressive investigations
 Do not lose crucial time to initiate treatement for
mucormycosis

40. Prophylaxis
©drseshasai
Neutropenic or immunosuppressive outbreaks –
Posaconazole 600mg/day (Controversy)
Surgery and Past h/o mucormycosis – Strong
recommendation

41.  Prognosis is generally poor but variable (late
diagnosis, extensive spread)
 All-cause mortality rate ~54%
 Mortality rates depends on:-Clinical form (body site
affected),Type of fungus
 Severity Underlying risk factors
 Use of surgical intervention
PROGNOSIS

42. CLINICAL FORM MORTALITY
1. Mucormycosis in HIV/AIDS~100%
2. Disseminated mucormycosis~90%
3. Rhino-cerebral mucormycosis~30-85%
4. Sinus mucormycosis~46%
5. Pulmonary mucormycosis~76%
6. Cutaneous mucormycosis~4-10%
7. Isolated renal mucormycosis~35%

43. Conclusion
©drseshasai
• More common in immunocompromised
• No specific clinical or radiological features
making diagnosis more difficult and challenging
• Diagnostic options are limited with variable
results
• Invasive diagnostics have more yield which is
not possible in some patients

44. Conclusion
©drseshasai
• Early diagnosis means early treatment and leading to
less mortality Rates
• Reversal of underlying factors, Surgery and Liposomal
amphotericin Bincreases cure rates
• Duration of treatment is highly individualized
• Posaconazole, Isuvaconazole can also be tried
• Salvage therapy in refractory or intolerant pts
• Adjunctive therapies need to proved in large trials and
standardized