Mucormycosis
By Dr. Bomkar bam
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.
Species
 Most common species are
1. rhizopus sp.
2. Mucor sp.
3. Rhizomucor sp.
Rhizopus sp
Mucor species
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.
MAJOR ROUTE OF
INFECTION
 INHALATION OF SPORES.
 INGESTION.
 TRAUMATIC INOCULATION.
 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
Types
©drseshasai
1. Rhino-cerebral – most common
2. Pulmonary
3. Disseminated – most deadly
4. Cutaneous/Soft tissue
5. Gastro Intestinal
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
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
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
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.
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
Complications
 Cavernous sinusthrombosis.
 Multiple cranial nervepalsies.
 Visualloss.
 Frontal lobeabscess.
 Carotid artery or jugular vein thrombosis
causinghemiparesis.
 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
RHINOCEREBRAL MUCORMYCOSIS
CT PNS – bony erosion of palate, septum and
maxilla.
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.
REVERSE HALO SIGN
Focal area of Ground Glass Opacity
surrounded by ring of consolidation
3. CUTANEOUS MUCORMYCOSIS
 Trauma is the predisposing factor.
 Invasive locally .
 May lead to necrotizing fascites - Mortality
upto 80%.
 Surgical debridement.
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
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
©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
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
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
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
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
©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
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.
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
©drseshasai
Duration of Treatment
Highly individualized
Near normalization of radiograph, negative
biopsy specimens and cultures, recovery from
immunosuppression
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%
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)
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
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.
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.
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
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
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
Prophylaxis
©drseshasai
Neutropenic or immunosuppressive outbreaks –
Posaconazole 600mg/day (Controversy)
Surgery and Past h/o mucormycosis – Strong
recommendation
 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
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%
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
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

Mucormycosis ppt by Dr. Bomkar bam ENT M.S.

  • 1.
  • 2.
    Introduction ©drseshasai • Mucormycosis (formerlyZygomycosis) – 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 commonspecies are 1. rhizopus sp. 2. Mucor sp. 3. Rhizomucor sp.
  • 4.
  • 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 ofmucormycosis 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 FACTORSAND 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  Onsetwith 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 (GOLDSTANDARD) 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.
  • 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 Focalarea 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 toDiagnosis ©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 beseen 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 Earlyadministration of active antifungal agents Reversal of underlying factors Complete removal of all infected tissues Use of various adjunctive therapies
  • 28.
    ©drseshasai PRIMARY ANTIFUNGAL THERAPY LiposomalAmphotericin-B first line recommended agent Fluconazole, Voriconazole, Itraconazole –Absidia species Posaconazole, Isuvaconazole can also be used as first line therapy
  • 29.
    Liposomal Amphotericin B Canbe 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 in2 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 Highlyindividualized 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 Ifdisease 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 HyperbaricOxygen – 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-AmBisomeTherapy 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 notmiss 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 immunosuppressiveoutbreaks – Posaconazole 600mg/day (Controversy) Surgery and Past h/o mucormycosis – Strong recommendation
  • 41.
     Prognosis isgenerally 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 commonin 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 diagnosismeans 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