management of Rino orbito- crebral- mucormycosis

1. MUCORMYCOSIS
by
Dr. Saptarshi Mondal
PGT ( M.S Ophthalmology)

2. 2
INTRODUCTION
Mucormycosis is an aggressive, opportunistic devastating fungal infection
commonly involving Nasal, Orbital and Cerebral regions. It is acquired primarily via
inhalation of spores through nasal route. I tis a rapidly progressive fungal disorder
and any delay in identification & management leads to high morbidity & mortality.
The fungus is angio-invasive causing occlusion of blood vessels, leading to tissue
necrosis. From the nasal cavity it enters the middle turbinate to reach maxillary
sinus. From there it erodes the floor of the orbit to reach the eye and further to
CNS. It can also cause pulmonary embolism but pulmonary mucormycosis is
relatively rare. Other forms of clinical presentation are Cutaneous, Gastrointestinal,
bone & joint infection and disseminated Mucormycosis.

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.
PREDISPOSING FACTORS
□Concurrent / Recently treated COVID -19
□Uncontrolled Diabetes Mellitus
□Inappropriate use of Steroids
oHigh doses of steroids
oUsing for prolonged periods
□Immunocompromised individuals
oMalignancy
oTransplant recipients
□Prolonged use of broad-spectrum antibiotics
□People under long standing Oxygen therapy
□Prolonged ICU stay
□People under mechanical ventilation
□Nosocomial
□Contaminated dirty line (health care associated mucormycosis)
□ICU gadgets - if not properly sterilized.

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CLINICAL PRESENTATION
I . Generalized Symptoms:
i. Headache
ii. Low Grade Fever
iii.Malaise & Lethargy
II. NasalSymptoms:
i. Nasal Stuffiness
ii. Foul smell
iii.Epistaxis
iv.Nasal Discharge: mucoid, purulent often blood -tinged, brownish, or blackish.
v. Nasal mucosa erythema, inflammation, purple or blue discoloration, white
ulcer, ischemia or escher.

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III. OcularManifestations:
i. Pain and redness around eyes, watering
ii. Periorbital Swelling / Discolouration
iii.Proptosis
iv.Diplopia
v. Diminution of vision
vi.Ptosis
vii.Ophthalmoplegia
viii.Facial Swelling & pain.
ix. Paresthesia, Numbness in the infra orbital region

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IV.Oral Manifestations:
i. Tooth ache /Loosening of teeth
ii.Blackish discolouration of oral mucosa
iii.Loss of sensation/ numbness over palatal region
V. Other Manifestations:
i. Chest pain, haemoptysis in case of pulmonary involvement
ii. Altered sensorium in case of cerebral involvement
iii. Facial palsy, Focal seizures, paralysis

7. DIAGNOSIS
Diagnostic Nasal endoscopy: Ulceration / Blackish necrotic eschar
Oral Examination: Black eschar on the Palate
Ocular Examination :
•Redness , watering
•Proptosis, Periorbital edema, ecchymosis
•Restricted eye movement, Ophthalmoplegia
•Decreased Corneal Sensation
•Fundus examination: cherry red spot or disc edema or both.
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8. Microbiology:
I.KOH smear
Specimen:
oNasal mucosal scraping in normal saline
oTissue biopsy from suspected mucosa in normal saline
Presence of broad aseptate hyaline hyphae (Ribbon Like) with irregular
branchingis indicative of Mucormycosis.
II. Fungal culture on Saboraud’s dextrose agar or Potato dextrose agar in a test tube at
30℃& 37℃. Any growth suggestive of fungi should be examined by making
Lactophenol cotton blue mount on a slide and examined under microscope for
identification of the fungus.

9. Pathology:
Specimen:
Debrided tissue for HPE to be sent to the Laboratory immediately in 10% Formalin.
Histopathological processing and staining done with routine H&E and special stains like
PAS & GMS.
Diagnosis is by visualizing the fungal hyphae based on morphology in the tissue.
If Exenteration or Sinus debridement is planned, HPE report from biopsy must be
obtained.
Radiology:
HRCT Scan of Orbit, Paranasal sinuses & Brain, with contrast if renal status
permits.MRI Paranasal sinuses and orbits (optional)
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START INJ.AMPHOTERICIN – B IMMEDIETELY WITHOUT
WAITING FOR INVESTIGATION REPORTS IN CASE OF
VERY HIGH CLINICAL SUSPICION.
General Investigations:
a.CBC
b.Fasting and Post Prandial Blood Sugar Monitoring
c.CRP, D-dimer, Ferritin
d.LFT
e.KFT
f.Electrolytes
g.ECG
h.H

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TREATMENT
The treatment approach demands multi-disciplinary approach involving General Physician/Infectious disease specialist,
ENT surgeon, Ophthalmologist, Neurologist, Neurosurgeon and Faciomaxillary surgeon depending on the extent of
involvement. Treatment should be early and aggressive.

14. Possible ROCM
Typical Signs and Symptoms in the clinical setting of concurrent or recently (< 6 weeks) treated COVID-19
No supportive evidence on
Diagnostic and Nasal
endoscopy and/or contrast
enhanced MRI/CT Scan
Probable ROCM
Supportive evidence Clinically and on
Diagnostic Nasal Endoscopy and/or contrast
enhanced MRI/CT Scan
No evidence on direct microscopy,
or culture or HPE
Proven ROCM
Supportive evidence Clinically and on
Diagnostic Nasal Endoscopy and/or
contrast enhanced MRI/CT Scan.
Confirmation on direct
microscopy, or culture or HPE
Repeat Nasal Endoscopy
after 24 hrs and MRI/CT
after72 hrs.
ROCM Unlikely
Clinically
Improving
Probably ROCM
Clinically Worsening
or new onset of
supportive evidence
Immediate induction therapy with liposomal Amphotericin-B with strict
metabolic control, and prepare the patient for further management as per
STAGING ,which are as follows:
Observe for 3
weeks

15. Possible ROCM
Typical Signs and Symptoms in the clinical setting of concurrent or recently (< 6 weeks) treated COVID-19
No supportive evidence on
Diagnostic and Nasal
endoscopy and/or contrast
enhanced MRI/CT Scan
Probable ROCM
Supportive evidence Clinically and on
Diagnostic Nasal Endoscopy and/or contrast
enhanced MRI/CT Scan
No evidence on direct microscopy,
or culture or HPE
Proven ROCM
Supportive evidence Clinically and on
Diagnostic Nasal Endoscopy and/or
contrast enhanced MRI/CT Scan.
Confirmation on direct
microscopy, or culture or HPE
Repeat Nasal Endoscopy
after 24 hrs and MRI/CT
after72 hrs.
ROCM Unlikely
Clinically
Improving
Probably ROCM
Clinically Worsening
or new onset of
supportive evidence
Immediate induction therapy with liposomal Amphotericin-B with strict
metabolic control, and prepare the patient for further management as per
STAGING ,which are as follows:
Observe for 3
weeks

16. Stage 1-2, 3a,3b
Predominant Sino-nasal manifestation with limited or
no orbital involvement. Vision preserved.
Stage 3c, 3d
Extensive orbital involvement
Early and aggressive debridement of PNS by an
appropriate surgical approach.
Stage 3a,3b
Retrobulbar inj. + sinus
irrigation with
amphotericin-B
Stage 4c,4d
Extensive CNS involvement
Stage4a,4b
No or limited CNS involvement
Disease progression,
worsening or orbital
component in < 72 hrs
Orbital exenteration +
aggressive debridement of
PNS
If systemic condition permits
Orbital exenteration +
aggressive debridement of PNS
Only supportive treatment if
surgery is not feasible
No disease progression
,Documented
improvement
Orbital exenteration
Sinus irrigation with Amphotericin-B
+Endoscopic or CT guided Debridement
Continue induction treatment with IV Amphotericin-B for minimum 4 weeks then step down treatment with oral
Posaconazole or Isavuconazole

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Other
Cerebral:
Anterior Table: Debridement Posterior Table : Cranialization
Debridement of osteomyelitic skull bone and involved cerebral parenchyma (Safe
Maximum Resection)
Pulmonary:
Cardio - Thoracic surgeon to decide on extent of Resection - Segmentectomy
or Lobectomy surgery.

18. Retrobulbar injection
Transcutaneous Retrobalbar injection of Inj. Amphotericin –B (3.5mg in 1ml of DDW
) can be given in Stage 3a,3b.
Complications: Rapid onset of Orbital Compartmental Syndrome

19. Eyelid- Sparing Technique is a better option ,if feasible

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MEDICAL
Drugs Recommended Dose Duration
Inj.Amphotericin B– Deoxycholate 0.75 -1mg/kg/day up to
total daily maximum of 50mg. 4 to 6 weeks depending on
severity
OR
Liposomal Amphotericin B 5mg/kg/day (nasal& orbital)
8 – 10mg/kg/day
(Cerebral)
OR
Inj.Amphotericin B – Lipid Complex 3 - 5mg/kg/day
FOLLOWED BY
Posaconazole 300mg once a day orally 2 to 4 weeks depending on
severity

21. ADMINISTRATION OF DRUG:
• Pre & Post hydration: 500ml Normal saline 2hrs before and after infusion of Amphotericin B
•To reduce the risk of renal toxicity and hypokalemia 500ml of Normal Saline +1 Amp (20mmol)
KCL can be given.
• Method of dilution:
For an average adult of 60kg body weight 300mg of LiposomalAmphotericin B is needed i.e., 6 vials.
Each 50mg vial of Liposomal Amphotericin B is reconstituted with 10ml of distilled water i.e., 60ml.
(Normal saline should NOT be used for reconstitution).
Test Dose: 1mg in 100 ml of DNS infused over 20 minutes & Observe for any allergic reaction
• Infusion: The 60ml of reconstituted solution is added to 300ml of 5% Dextrose which is infused
intravenously over a period of 2 hours.
•If there is fluid overload, use 250ml pre/post hydration or skip post-hydration.
•If hyperchloremic, may use Normosol instead of NS.
•Protect from light during administration. 6

22. .
Monitoring:
Serum Creatinine, Electrolytes and CRP to be monitored every alternate day
throughout the course of treatment with Amphotericin B.
Salvage therapy:
In patients who cannot tolerate Amphotericin B due to severe renal impairment /
allergy / selected cases for cerebral mucormycosis,
1. Inj. Posaconazole : 300mg IV BD / oral /Day 1 - followed by
300mg OD X 4 – 6 weeks
(or)
Inj. Isavuconazole : 200mg IV TID /oral X 2 days - followed by
200mg IV OD /oral X 4 – 6 weeks
6

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SURGICAL
ENT:
Surgical Debridement of the Dead Necrotic Tissue to prevent further progression
and spread of lesion.
1). Nasal & Sinus involvement (Without bony involvement)
Endoscopic sinus surgery debridement of the involved sinuses.
End point of surgery: Bleeding from normal Tissue after removal of Necrotic Tissue.
Patient complaints of pain if the surgery is done under LA.
2). Nasal & Sinus involvement (With bony involvement)
Endoscopic sinus surgery debridement with removal of devitalized
bone.
3). Sinus involvement with early loss of vision:
Endoscopic sinus surgery + Trans cutaneous Retro Bulbar
Amphotericin B 1ml of 3.5 mg per ml.

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Ophthalmology:
Stage 3a, 3b – Endoscopic orbital decompression with sampling of retro orbital
fat for HPE.
Stage 3c - Exenteration
Cerebral:
Anterior Table: Debridement Posterior Table : Cranialization
Debridement of osteomyelitic skull bone and involved cerebral parenchyma
(SafeMaximum Resection)
Pulmonary:
Cardio - Thoracic surgeon to decide on extent of Resection - Segmentectomy
or Lobectomy surgery.

25. Other Proposed Therapies for Mucormycosis

26. Other Proposed Therapies for Mucormycosis
1) Echinocandins ( Capsofungin)
Combination therapy with Liposomal Amphotericin-B ,shows significant improvement in
outcome in ROCM. Enhanced exposure of Beta-glucan on the fungal surface, which result in
immune stimulation , may be one of the mechanism of action.
2)Deferasirox ( Iron Chelating agent) in combination with Liposomal Amphotericin-B ,
synergistically improve survival rate among MICE by reducing fungal load in brain. Chief adverse
effect is renal toxicity.
3) Pro-inflammatory cytokines , such as interferon-y and granulocyte macrophage colony
stimulating factor , enhance ability of granulocytes to damage the agents of mucormycosis.
4) Hyperbaric Oxygen Therapy

27. FOLLOW UPAFTER SURGERY:
•Relook nasal endoscopy of weekly intervals for 6 weeks to assess epithelization of
nasal cavity and to remove any residual necrotic bone.
•Daily nasal douching with diluted Amphotericin B solution (50mg vial in
500ml of normal saline)

28. PREVENTIVE MEASURES:
1. Personal Hygiene
a.Good Oral Hygiene
b.Periodical change of Bed Linen
2. Medical Management
a.Judicious use of steroids at right time, in right dose and for right period.
i. No steroids if patients are not hypoxic
ii. Avoid prescribing post-discharge Steroids.
b. Strict diabetes control (110-180mg%) with Insulin and Oral
Hypoglycemic Agents.
I. GRBS testing of every hospitalized patient at least once a day to monitor
Blood sugar levels.
II. Proper management of Diabetic Keto-Acidosis.

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3. Hospital / Institutional level
a.Use clean, sterile water for humidifiers during oxygen therapy
b.Disinfecting all gadgets in ICU regularly
c. NOT TO REUSE disposable oxygen delivery devices likeNasal prongs,
Face masks etc.
4. Advice to the Patient and care-giver at the time of discharge:
a.Monitor blood glucose level in diabetics
b.Inform the patients about early symptoms & signsof
Mucormycosis:
i. Nasal blockage/Blood-tinged nasal discharge
ii. Pain in the eye/swelling of the eye /double vision
iii. Headache / numbness over theface
iv.Tooth ache/loosening of teeth/discomfort during chewing
v. Follow up on Day-7 and 3 weeks after discharge.

30. POST PRANDIAL/PREDINNER
PRANDIAL/ PREDINNER/ RANDOM
CONTACT INCHARGE DIABETOLOGIST /
COVID- 19 & MUCORMYCOSIS
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32. Thank you