Brief description about mucormycosis ,approach to diagnosis and management

1. Mucormycosis
Sreeraj Vasudevan.MD.DM

2. MUCOR MYCOSIS:
Angioinvasive disease caused by
SAPROPHYTIC fungi of the order
Mucorales
Most common species :
• Rhizopus (mc)
• Mucor
• Rhizomucor,
• Cunninghamella
• Apophysomyces
• Saksenaea
• Absidia
14 cases /100000

3. From where we get the infection?
Sporangiospores: It is everywhere

4. Route of Infection:
Spore Inhalation
Post Trauma
Iatrogenic
Burns
Diabetics Immunosuppression
Transplant Pre term Neonate
Malnourishment

5. Pathophysiology
Rapid extension

6. Who are at risk
• Diabetes-Especially patients with DKA
• Hematological malignancy
• BMT/Solid organ transplant
• Long term immunosuppression
• Pre treatment with Voriconazole
• ??COVID
• CKD [Indian]
• Malnourishment [Indian]
• COPD [Indian]
• Pulmonary TB[Indian]

7. COVID x Mucormycosis
Two Host Factors
• Hyperglycemia
• Acidosis
GRP78-Increased
expression of
endoplasmic
reticulam
Increase Virulence
Temporary cessation of
transferrin binding of serum Iron
Increased Serum free Iron : Uptake by
Siderophore
Decreased
Neutrophil
Function
Decreased
chemotaxis,
Phagocytosis
Deceased intracellular
killing
Mucorales:
Keto Reductase
Consumption of Ketone
body for energy
Majority of infection in Diabetics occur during DKA
Increased
endothelial GRP78
Rhizopus angio
invasion through
this receptor

8. COVID x Mucormycosis
• Two peaks:
• During admission with Severe Illness
• Post discharge of Severe illness upto 4 weeks

9. Spectrum of Infection
• Rhino –Orbital- cerebral
• Pulmonary
• GIT
• Cutaneous
• Disseminated
• Isolated Renal

10. Rhino Orbital Cerebral Mucormycosis
Para Nasal Sinuses: Onset with nasal stuffiness ,epistaxis and facial
pain,headache
Orbital Extension:proptosis , chemosis and ophthalmoplegia.
Cerebral Extension:confusion,FNDS
• Black necrotic eschar on the nasal turbinates or palate
• Fever

11. Rhino Orbital Cerebral Mucormycosis
• CT Paranasal Sinuses: Sinusitis,Bone destruction,Orbital extension
• MRI Brain to detect Intracranial extension,Orbital Extension
• Poor Prognosis:
• Focal neurological defect
• Cavernous sinus thrombosis
• Brain invasion

12. Rhino Orbital Cerebral Mucormycosis

13. Rhino Orbital Cerebral Mucormycosis
• Complications:
• Neurological Deficit
• Blindness
• Cerebral Thrombosis,Infaction,Stroke
• Cavernous Sinus Thrombosis
• Carotid Artery Thrombosis
• Disfigurement

14. Pulmonary Mucormycosis
• Fever
• Cough
• Hemoptysis : May be massive
• May be associated with Rhinocerebral mucormycosis
• Often delay in diagnosis
• Surgical debridement often not possible

15. Pulmonary Mucormycosis
• In Immunocompromised Patients:
Reverse Halo Sign
Halo Sign

16. Pulmonary Mucormycosis
• In Immunocompetent Patients:
• Radiologically indistinguishable from bacterial consolidation
• LARGE CONSOLIDATION
• MULTIPLE NODULES [>10]
• PULMONARY INFARCTION
• PLEURAL EFFUSION
• ASSOCIATED SINUSITIS

17. Diagnosis
Biopsy Specimen:1 half :KOH preparation
• Sterile site : KOH preparation & Culture
• Culture:difficult to grow
Hyphae are broad ,> 6 to 16 micrometer

18. Diagnosis
Second Specimen for HPE
• HPE: Diagnostic
• Need to document
• Broad Aseptate Hyphae
• Tissue Inflammation
• Angioinvasion
• Necrosis
Hyphae are broad ,> 6 to 16 micrometer
PCR
MALDI -TOF

19. SWAB FROM NASAL/SINUS CAVITY :
NOTDIAGNOSTIC
BAL KOH: NOT DIAGNOSTIC

20. Treatment of Rhino cerebral mucormycosis
ENT
Ophthalmology
Radiology
Maxillofacial
Drug treatment
Team Effort

21. Medical Management
Initial Therapy
Step:1
• Reduce /Stop Immunosuppression/Steroid
• Tight sugar control
• Control Acidosis

22. Medical Management
Initial Therapy
Step 2:
• Liposomal Amphotericin B
• 5-10mg/Kg Daily for 3 to 6 week
• Dilute in 5%Dextrose 500ml infusion over 4 to 6 hours
• Monitor Creat,Potassium,Magnesium
• Duration: 3-6weeks
• Problems:
• Need central line
• Refractory Hypokalemia
• Cost :20,000 /day
• Delay in LAMB:Increased Mortality

23. Alternate to LAMB:
• Conventional AMB
• 1 to 1.5mg/Kg
• Renal dysfunction
• Electrolyte disturbance: Same as LAMB
• Pre /Post Hydration with 500ml NS :Reduce incidence of renal dysfunction
• Allergic reaction:
• Premediaction with Inj.Avil/Tab.Paracetamol reuces the allergic reaction
• Cost =500Rs/Day

24. If baseline renal dysfunction
• Isavuconazole
• Posaconazole

25. Post initial Amphotericin
• After 3 to 6 weeks of AMB if radiologically stable disease
• Oral secondary Px with Posacoanzole/Isavuconazole
• Therapeutic drug level monitoring
• Duration 3 to 6 months
Posaconazole suspension also available: Absorption Issue
Cost of therapy : Expected around 15000 to 20000 per 4 weeks

26. Others
• Iron chelation
• Hyperbaric Oxygen
• Statins:

27. Mortality
• Even with treatment :Ranges from 60-85%
• Delay in Surgical debridement in ROM more than 6 days: Mortality
increases by 50%.
• Delay in AMB : Mortality increases by 60-70%
• ROCM: Post debridement Debility is concern
• Most loss eye

28. Cost of treatment :
=10 lakh INR per person

29. Prophylaxis: Patient side:
Avoid fresh flowers

30. Prevention of Infection: Environmental
Modification:
AML Induction
Ward/AIIMS

31. Prevention of Infection: Environmental
Modification:
• Recommendations are for Invasive Aspergillosis
• Air Spore Quantification: Conidial count
• Accepted level in UNPROTECTED room: <25 CFU/mm3

32. Environmental modification
• Regular monitoring of spore count:especially after construction
• Adequate air circulation
• Maintain air filters
• Avoid moisture;Avoid Water Leak
• Positive Pressure ICU-Not practical
• Laminar flow- Not practical
• Adequate Autoclaving
• Avoid construction activity near ICU
• H2O2 Based sanitisation
• Frequent fumigation
• Oxygen regulator clean and dry: Fill with distilled/RO water

33. Summary
• Control sugars and acidosis
• Reduce the steroid abuse
• Ask the patients to wear N95 mask
• Keep our ICU dry/fumigated
• Look in to the oropharynx daily
• Follow up patient post discharge
• Early Sx and Medical Treatment: Life Saving

34. Our small success story
• 48 year old male with AML,CKD
• Developed black lesion in hard palate and right upper alveolus
Just after Sx
30/12/20
17/05/21
Initail Bx was negative.
He was put on LAMB 5mg/kG
for 6 weeks
Surgical debridement on
30/12/20:HPE: Mucormycois.
CURRENTLY ON
POSACONAZOLE SECONDARY
PX.
23/11/20

35. Our Failure story
No Age/Sex Ds Mucor Diabetes Sx outcome
1:11/12/19 57/M APML Rhino-orbital No Yes Died -2nd Post
OP day : Brain
Extension
2: 7/5/20 16/F R-AML Rhinoorbital No No Died
3:2/12/20 60/M B-ALL Rhino orbital
Skin
Pulmonary
Yes No Died
4: 3/1/21 43/M AML Rhino orbital No No Died
5:30/12/20 48/M AML Rhinoorbital No Yes Surviving
Mortality : 80%
Incidence: 5/ 52 Leukemia

36. Thank You..