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Mucormycosis.pptx
- 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
- 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..
Editor's Notes
- Rhizopus invades the endothelium via binding of fungal CotH proteins to the host receptor GRP78. Here, we report that surface expression of GRP78 is increased in endothelial cells exposed to physiological concentrations of β-hydroxy butyrate (BHB), glucose, and iron that are similar to those found in DKA patients.