management protocol for mucormycosis
TRANSCRIPT
अखिल भारतीय आयरु्विज्ञान ससं्थान, एम्स ऋर्िकेश
All India Institute of Medical Sciences Rishikesh, Uttarakhand, India, 249203
@Multidisciplinary Mucor management team_Version 1.0_16.05.2021 (AIIMS Rishikesh) 1
Management Protocol For Mucormycosis
A diagnosis we cannot afford to miss
Institutional Strategies: 1. A multidisciplinary team is constituted for managing mucormycosis cases with following
responsibilities:
Assessing time to time situations
Providing guidelines for prevention and treatment
Managing patients admitted at AIIMS Rishikesh
To give public-oriented messages for awareness
2. All mucormycosis cases will be admitted in a separate Mucor ward (having CCU beds, HDU,
general beds) and it will be managed by multidisciplinary team comprising department of ENT,
Medicine, Oral and maxillofacial surgery, Ophthalmology, Neurosurgery, Pediatrics, Paediatric
surgery, Microbiology, Pharmacology, Community and Family Medicine, and other departments as
per organ involvement.
4. Separate ward, OT, or extra OT are to be arranged as per clinical load.
5. Multidisciplinary team will facilitate steps for prevention and early diagnosis with rapid initiation
of antifungal therapy and aggressive early surgical debridement with optimal correction of co-
morbidities.
अखिल भारतीय आयरु्विज्ञान ससं्थान, एम्स ऋर्िकेश
All India Institute of Medical Sciences Rishikesh, Uttarakhand, India, 249203
@Multidisciplinary Mucor management team_Version 1.0_16.05.2021 (AIIMS Rishikesh) 2
Types and symptoms:
Mucormycosis is an aggressive, angioinvasive fungal infection, acquired primarily vial inhalation of
environmental sporangiospores (3-11micron) in immunocompromised hosts or direct entry during
trauma, and affects these hosts with severe metabolic conditions.
1. Rhino-orbito-
cerebral
mucormycosis
(ROCM)
Nasal stuffiness, foul smell, epistaxis, nasal discharge, unilateral
facial oedema, diplopia, proptosis, pain and redness around eyes
and/or nose, loss of vision, restriction of eye movements, palatal or
palpebral fistula, blackish discolouration over bridge of nose/palate,
prolonged Fever, headache, toothache, loosening of teeth, jaw
involvement, altered mental status
2. Cutaneous and soft
tissue
mucormycosis
Erythema, induration, then black eschar at trauma/puncture site,
muscle pain with deeper involvement
3. Pulmonary
mucormycosis
Refractory fever on broad-spectrum antibiotics, non-productive
cough, progressive dyspnea, pleuritic chest pain
4. Gastrointestinal
mucormycosis
Fever, bleeding per anus, masslike lesions, then perforation of gut
5. Mucormycosis of
bones and joints
Local pain and tenderness, cellulitis, fever is rare
6. Disseminated
mucormycosis
Symptoms vary as per site of involvement, mostly associated with
pneumonia
RISK FACTORS-
1. Case of concurrent or recently (<6 weeks) treated Severe COVID-19
2. Uncontrolled diabetes mellitus, Chronic granulomatous diseases, HIV/AIDS, or primary
immunodeficiency states
3. Use of Immunosuppression by steroids (any dose use for >3weeks or high dose >1week),
Tocilizumab, other immunomodulators, or therapy used with transplantation
4. Prolonged neutropenia
5. Trauma, Burns, IV drug abusers
6. Prolonged ICU stay
7. Post-transplant/malignancy (solid or Hemopoietic)
8. Voriconazole therapy, Deferoxamine or other iron overloading therapy
9. Contaminated adhesive bandages, wooden tongue depressors, adjacent building construction,
and hospital linens
10. Renal failure, diarrhea, and malnutrition in low-birth-weight infants/even children/adults
अखिल भारतीय आयरु्विज्ञान ससं्थान, एम्स ऋर्िकेश
All India Institute of Medical Sciences Rishikesh, Uttarakhand, India, 249203
@Multidisciplinary Mucor management team_Version 1.0_16.05.2021 (AIIMS Rishikesh) 3
DIAGNOSIS- Symptoms + Investigations
Investigations 1) Lab parameters:
CBC, ESR, FBS, PPBS, HbA1C, LFT, KFT with electrolytes, Viral markers (HIV/HBV/HCV)
2) Diagnostic nasal endoscopy: crusting, debris, scabbing, granulation, discoloured mucosa
(either darkened or pale), decreased bleeding and insensate mucosa
3) Imaging:
CECT Nose and PNS: Erosion and thinning of bones, Enlargement of masticatory muscle,
Mucosal thickening of sinuses Changes in Fat Planes
CEMRI Brain Orbit and Face: Optic neuritis, Intracranial involvement, Cavernous sinus
thrombosis, Infratemporal fossa involvement
4) KOH staining & microscopy - Direct microscopy using fluorescent brightener and
histopathology with special stains (e.g. PAS and GMS)
Typical findings: non-septate/pauci-septate, ribbon-like hyphae (at least 6–16μm wide), Vessel
occlusion
5) Histopathology- haemorrhagic infarction, coagulation necrosis, angioinvasion, infiltration by
neutrophils (in non-neutropenic hosts), and perineural invasion.
6) Fungal culture- Routine media at 30°C and 37°C
Typical findings: cotton white or greyish black colony
Sample collection and transportation:
Test (all endoscope
assisted)
Sample to be collected in To diagnose
KOH
Saline Presence of Fungi
Fungal culture
Saline Type of Fungi
Histopathology
10% Formalin Fungus/Bony lesions/
malignancy
Specimens should be collected aseptically in sterile containers and transported to the laboratory
within 2 hours.
Avoid sending swabs if pus or sterile body fluid can be aspirated or when tissue can be
obtained. Swabs may give false negative reports.
Never use dry swabs to collect specimen.
Completely filled TRF is required for accurate reporting.
Please write the Name & mobile number of the attending physician (JR/SR/Faculty) in legible
handwriting to facilitate prompt communication regarding reports
अखिल भारतीय आयरु्विज्ञान ससं्थान, एम्स ऋर्िकेश
All India Institute of Medical Sciences Rishikesh, Uttarakhand, India, 249203
@Multidisciplinary Mucor management team_Version 1.0_16.05.2021 (AIIMS Rishikesh) 4
Sample collection according to the site of Mucormycosis
Specimen Collection Unacceptable specimen
ROCM Scraping or exudate from nares, hard palatal lesions, sinus material, biopsy from extracted tooth socket area. Endoscopic collection of debrided tissue/biopsy
Nasal dry swabs
Cutaneous Aspirations collected with sterile needle and syringe from undrained abscess. Pus expressed from abscess opened with scalpel; transported to laboratory either in sterile container/syringe and needle Tissue should be collected from both centre and edge of the lesion.
Swab or materials from open wound dry swabs
Pulmonary Sputum
Bronchial brush washing/ broncho-alveolar lavage (BAL) Lung biopsy- Collected by bronchoscope, Fluoroscope guided trans-thoracic needle aspiration or open lung biopsy
Saliva Saline wash
Gastrointestinal mucormycosis
Endoscopic biopsy of the lesions Faeces
Renal mucormycosis
Biopsy of the lesions Urine
TREATMENT-
Possible or Proven ROCM
Urgent surgical debridement
Strict glycemic control
Inj Amphotericin B (1.0-1.5 mg/kg/day)
or
Inj Liposomal amphotericin B
5-10mg/kg/day (intra cranial involvement-10 mg/kg /day)
or
Inj Amphotericin B lipid complex 5mg /kg/day
Continue treatment till resolution of initially indicative findings on imaging and reconstitution
of host immune system.
अखिल भारतीय आयरु्विज्ञान ससं्थान, एम्स ऋर्िकेश
All India Institute of Medical Sciences Rishikesh, Uttarakhand, India, 249203
@Multidisciplinary Mucor management team_Version 1.0_16.05.2021 (AIIMS Rishikesh) 5
Second line- AZOLE Derivatives (Step Down or Salvage Therapy) Posaconazole is broad-spectrum azoles available in both parenteral and oral formulations.
Dosage:
- 200 mg four times per day
- Alternatively, posaconazole delayed-release tablets (300 mg every 12 hours on first day, then
300 mg once daily) taken with food.
Amphotericin B administration and monitoring protocol
Drugs Recommended Dose
Duration
Inj Amphotericin B
Deoxycholate (C-
AmB):
1.0-1.5 mg/kg/day
14 to 21 days depending on severity/till clinical resolution and radiological stabilization; after 14days of therapy, shift to oral Posaconazole if clinically stable.
Inj Liposomal
amphotericin B
(LAmB):
5-10mg/kg/day
Inj Amphotericin B
lipid complex (ABLC)
5mg/kg/day
Inj Liposomal amphotericin B (LAmB):
Premedication Complications K + correction
Urea Creatinine Na K Mg
Amphotericin Monitoring Chart(To be filled daily) Patient name : …………………………………..
Serum ElectrolytesCumulative
dose
Dose
givenName of the drug Date
Starting
time
Ending
timeSr. No.
Test dose
•Inj. Liposomal Amphotericin- B 1 vial (50 mg) to be diluted in 12 ml of the diluent and 0.25ml (1 mg) of solution made, to be mixed in 100ml Dextrose and to be infused in 30 minutes.
•Observe for fever and reactions
Pre-hydration
•500 mL NS over 30 minutes
•To reduce the risk of renal toxicity and hypokalaemia :- 500ml Normal Saline + 1 Amp (20mmol) KCL
Therapeutic dose
•5mg-10 mg /kg/day Amphotericin B in 500 mL D5 with 10 Units HIR over 3 hrs (To be covered in black sheet)
Post Hydration
•500 mL NS over 30 minutes
Post dose
•KFT with Serum electrolytes after Every dose of Amphotericin B
•Fill Amphotericin monitoring chart
अखिल भारतीय आयरु्विज्ञान ससं्थान, एम्स ऋर्िकेश
All India Institute of Medical Sciences Rishikesh, Uttarakhand, India, 249203
@Multidisciplinary Mucor management team_Version 1.0_16.05.2021 (AIIMS Rishikesh) 6
Inj Amphotericin B Deoxycholate(C-AmB)
Cockcroft-Gault formula for estimating creatinine clearance (CrCl)
CrCl (male) = ([140-age] × weight in kg)/(serum creatinine × 72)
CrCl (female) =([140-age] × weight in kg)/(serum creatinine × 72) × 0.85
In case of nephrotoxicity
Crcl <10 ml/min: 0.5-0.7 mg/kg IV q24-48hr
Consider other antifungal agents that may be less nephrotoxic
Intermittent hemodialysis: 0.5-1 mg/kg IV q24hr after dialysis session
Continuous renal replacement therapy: 0.5-1 mg/kg IV q24hr
Pediatric conversions (<30kg):
Dose of amphotericin B is same
Fluid dilution – 10-12mg/Kg
Oral Posaconazole – 18-24 mg/kg/day in 3-4 divided doses; IV doses – 18-24 mg/kg/day in 2-3
divided doses
Inj Amphotericin B lipid complex (ABLC)
Test dose
• 1 mg in 100 mL D5 over 20 minutes
Pre-hydratio
n
• 500 mL NS over 30 minutes
Therapeutic dose
• 1.0-1.5 mg/kg/day Amphotericin B in 500 mL D5 with 10 Units HIR over 3 hrs (To be covered in black sheet)
Post Hydratio
n
• 500 mL NS over 30 minutes
Watch for:
• Urine output , Renal function Test (pH, Bl. Urea, S. Creatinine, Electrolytes)
• Fill Amphotericin monitoring chart
Test dose
•1 mg in 100 mL D5 over 20 minutes
Pre-hydration
•500 mL NS over 30 minutes
Therapeutic dose
•5mg /kg/day Amphotericin B in 500 mL D5 with 10 Units HIR (Human Insulin Regular) over 3 hrs (To be covered in black sheet)
Post Hydration
•500 mL NS over 30 minutes
Post dose
•KFT Serum electrolytes after Every dose of Amphotericin B
•Fill Amphotericin monitoring chart
अखिल भारतीय आयरु्विज्ञान ससं्थान, एम्स ऋर्िकेश
All India Institute of Medical Sciences Rishikesh, Uttarakhand, India, 249203
@Multidisciplinary Mucor management team_Version 1.0_16.05.2021 (AIIMS Rishikesh) 7
SURGICAL MANAGEMENT
Early surgical debridement (all patients)
Transcutaneous 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
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 indication of exenterationExenteration 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
अखिल भारतीय आयरु्विज्ञान ससं्थान, एम्स ऋर्िकेश
All India Institute of Medical Sciences Rishikesh, Uttarakhand, India, 249203
@Multidisciplinary Mucor management team_Version 1.0_16.05.2021 (AIIMS Rishikesh) 8
PREVENTION-
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.
Enviromental cleanliness to have NO exposure to decaying organic matters like breads/fruits/vegetables/soil/compost/excreta/etc
Control hyperglycemia
Glucose monitoring in COVID-19 patients requiring steroid therapy
Optimally steroid usage - right timing of initiation, right dose, and right duration
Use clean distilled water for humidifiers during oxygen therapy
Use antibiotics/antifungals only and only when indicated
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
Simple tests like pupillary reaction, ocular motility, sinus tenderness and palatal examination should be a part of routine physical evaluation of a COVID-19 patient.
अखिल भारतीय आयरु्विज्ञान ससं्थान, एम्स ऋर्िकेश
All India Institute of Medical Sciences Rishikesh, Uttarakhand, India, 249203
@Multidisciplinary Mucor management team_Version 1.0_16.05.2021 (AIIMS Rishikesh) 9
REFERENCES-
1. Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases - 9th Edition. 2020. E-Book
2. Oliver A Cornely, Ana Alastruey-Izquierdo, Dorothee Arenz, Sharon C A Chen, Eric Dannaoui, Bruno Hochhegger et al. Global guideline for the diagnosis and management of mucormycosis: an initiative of the European Confederation of Medical Mycology in cooperation with the Mycoses Study Group Education and Research Consortium.The Lancet Infectious Diseases. 2019;19 (12):e405-e421. Available from: https://doi.org/10.1016/S1473-3099(19)30312-3.
3. Mucormycosis (zygomycosis): Available from: https://www.uptodate.com/contents/mucormycosis-zygomycosis?source=history_widget.
4. Evidence Based Advisory In The Time Of Covid-19: Available from: https://www.icmr.gov.in/pdf/covid/techdoc/Mucormycosis_ADVISORY_FROM_ICMR_In_COVID19_time.pdf
5. Honavar SG. Code Mucor: Guidelines for the Diagnosis, Staging and Management of Rhino-Orbito-Cerebral Mucormycosis in the Setting of COVID-19. Indian J Ophthalmol 2021;69:1361-5.
6. Treatment Protocol For Mucormycosis In Adult Patients- By Expert Committee of Civil Hospital, Ahmedabad
ACKNOWLEDGMENT
I would like to thank Director and CEO Padmashri Prof Ravi Kant for providing me opportunity to be part of
institute MUCOR management team as Team leader. I would like to thank MS Prof Binaya Kumar Bastiya
DHA Prof U.B.Mishra, and Dean (A) Prof Manoj Gupta for their invaluable support. I would like to thank Dr
PK Panda, COVID nodal officer, Department of internal medicine for his invaluable support. I would like to
thank my faculty colleagues in various departments. I would like to thank the Senior Residents and Junior
Residents of Department of ENT and other departments and Nursing officers, ward attendants, Guards, and
housekeeping staffs posted in MUCOR ward for their role in management of the patients. Last I would like
to acknowledge the role of the following departments in preparing the institute protocol for MUCOR
management at present:
1. Department of ENT, AIIMS Rishikesh 2. Department of Internal Medicine, AIIMS Rishikesh 3. Department of Ophthalmology, AIIMS Rishikesh 4. Department of Maxillofacial Surgery, AIIMS Rishikesh 5. Department of Neurosurgery, AIIMS Rishikesh 6. Department of Microbiology, AIIMS Rishikesh 7. Department of Anaesthesia, AIIMS Rishikesh 8. Department of Pediatrics, AIIMS Rishikesh 9. Department of Pediatric Surgery, AIIMS Rishikesh 10. Department of Pharmacology, AIIMS Rishikesh 11. Department of CFM, AIIMS Rishikesh