brief description about mucormycosis

1. Mucormycosis
Sekhar babu. B
postraduate
Department of pharmacology

2. OVERVIEW
• Introduction
• Riskfactors
• Etiopathogenesis
• Clinical presentation and manifestations
• Radiographical features
• Histopathogical features
• Diagnosis
• Treatment

3. Introduction
• American pathologist R.D.Baker coined the term mucormycosis
• Insidious fungal infection caused by members of mucorales and
Zygomycotic species
• Angioinvasive fungal infection
• Opportunistic fungal infection of the zygomycete family
• First described in 1885, Paltauf described in Germany a patient who
died of cancer and in whom the right lung showed a hemorrhagic
infarct with fungal hyphae and a few sporangia, described as Mycosis
Mucorina

4. Risk factors
• Uncontrolled diabetes mellitus (keto acidosis)
• Steroid use
• Extremes of age
• Neutropenia
• Hematological malignancy
• Renal insufficiency
• Organ transplantation
• Iron overload

5. Etiopathogenesis
• Gain entry to a susceptible host through inhalation, ingestion of
contaminated food, or abraded skin
• Types :
1. Rhinocerebral mucormycosis
2. Pulmonary mucormycosis
3. Gastrointestinal mucormycosis
4. Cutaneous mucormycosis
5. Disseminated mucormycosis

6. • Angioinvasive property, resulting in vascular thromboses and ultimately
tissue necrosis
• Interaction between a spore-coating protein family (CotH) on Rhizopus
spp. surface and endothelium glucose regulator protein 78 (GRP78)
expressed at the surface of endothelial cells.
• Triggers host cell injury and subsequent fungus hematogenous
dissemination.

7. • Elevated levels of serum glucose, iron, and ketone bodies
• Increase fungal growth and induce the expression of GRP78 and CotH
• Resulting in increased ability of Rhizopus to invade host tissues and
explaining the susceptibility of diabetic and deferoxamine treated
patients to mucormycosis

8. • Decreased numbers and impaired function of monocytes and
neutrophils

9. Clinical presentations and manifestations
• Superficial and visceral – external ear, finger nails and skin
• Localised and disseminated – pulmonary, gastrointestinal and
rhinocerebral
• Symptoms- fever, blindness, exophthalmos, nasal bleed, facial
paralysis
• Reddish- black nasal turbinate and septum with nasal discharge
• Progression into cranial vault leads to blindness, lethargy and seizures
and leads to death

11. Radiographic features
• MRI- opacification of sinuses with patchy effacement of bony walls of
sinus
• “Black turbinate sign” area of non enhancing mucosa in cavernous
sinus thrombophlebitis
• CT- thickened mucosa or clouded sinuses, densely crowded
extraocular muscles, enlarged compactness of orbital apex, propotosis
and inflammation of optic nerve, micronodules in lungs.

12. Histopathological features
• Extensive necrosis with numerous large branching pale – staining, wide,
nonseptal hyphae with branching at right or obtuse angles.
• Round or ovoid sporangia are seen.
• Thin walled hyphae with non parallel sides, branching irregularly and often
with bulbous hyphal swelling
• Signs of angioinvasion and infarction is seen
• Infiltration of neutrophils and with chronic infection granuloma formation is
observed

13. Diagnosis
• Evaluation of clinical manifestations
• Magnetic resonance imaging modalities
• Computed tomography
• Cytological and histological examination

14. • Polymerase chain reaction – detects DNA in the early course of
infection, detect Mucorales DNA in serum samples from 90% of
patients up to three days before mucormycosis diagnosis
• Gold standard analytic technique for confirmation is the tissue based
analysis

15. Treatment
• Rapid accurate diagnosis
• Surgical debridement
• Administration of drugs
• Adjunctive application of hyperbaric oxygen
• Recombinant cytokines
• Transfusion of granulocyte

16. • Monotherapy shows high mortality rate
• Choice of “Combination therapy”
• Antifungal therapies include Amphotericin B (AmB),
• Liposomal AmB (5-10mg/kg),
• AmB lipid complex,
• AmB colloidal dispersion,
• Posaconazole (400mg bid)

17. • Second-line treatment includes
• Combination of caspofungin and lipid AmB,
• Mixture of lipid AmB and Posaconazole
• Soft tissues, cerebral disseminated, localized pulmonary lesion and
rhino-orbito- types surgical treatment should be considered
• Correction of risk factors

18. Indication of emergency surgery
• Debridement has to be extensive, involving all necrotic areas for
rhino-oculo-cerebral infection, and repeated surgical procedures are
recommended to achieve local control and improve outcome
• Surgical treatment reduced mortality by 79%

19. ANTIFUNGAL TREATMENT
• Amphotericin B and its lipid formulations
• Posaconazole
• Isavuconazole

20. Amphotericin B
• Polyene macrolide
• Streptomyces nodosus
• Broad spectrum antifungal
• Antifungal used to treat fungal infections in neutropenic patients,
cryptococcal meningitis in HIV infection, fungal infections, and
leishmaniasis
• Fungistatic or fungicidal depending on the concentration obtained in
body fluids and the susceptibility of the fungus

21. mechanism of action

22. Pharmacokinetics
• Oral absorption – negligible
• Amphotericin B deoxycholate complex suspension prepared with bile salt
deoxycholate , administered by intravenous route
• More than 90% bound with plasma proteins (beta lipoproteins)
• T1/2 terminal phase of elimination is 15 days
• Metabolism – renal
• Eliminated through bile and urine

23. Lipid formulations

24. • Lipid delivery vehicles – high affinity for fungal cholesterol
• Reduce toxicity, maintain efficacy
• The duration of the first-line antifungal treatment is still a matter of
debate and should be determined on an individual basis and adjusted
based on the underlying condition

25. Toxicity due to I.V. infusion
• Fever, chills, muscle spasms, vomiting, headache, hypotension due to
release of cytokines; IL, TNF-ALFA
• Phlebitis
• Bronchospasm or anaphylaxis is rare
• Hypoxia and hypotension in patients with cardiac and pulmonary
disease

26. Toxicity due to prolonged use
• Nephrotoxic – dose dependant- azotemia, hypokalemia,
hypomagnesemia, reduced GFR, renal tubular acidosis
• Anemia due to reduced production of erythropoietin
• CNS- headache, nausea, vomiting, convulsions nerve palsies

27. Posaconazole
• Triazole antifungal
• Only azole significantly active against mucormycosis
• Absorption increased by fatty meal and at low Ph
• Rapidly distributed into tissue
• Half life more than 24 hours
• Metabolised by CYP2C19 undergoes glucoronidation
• Excreted unchanged in faeces
• Dose: 400mg twice a day

29. • Uses:
Invasive aspergillosis
Candidiasis
Mucormycosis
Chromomycosis

30. Adverse effects
• Nausea
• Vomiting
• Diarrhoea
• Abdominal pain
• Headache
• dizziness

31. Isavuconazole
• Triazole antifungal with broad spectrum of activity and good safety profile
• Isavuconazonium sulfate is a water-soluble pro-drug, hydrolyzed to the
triazole isavuconazole after oral or intravenous administration
• Mechanism of action similar to posaconazole
• Highly protein bound predominantly to albumin
• Longer half life- oral 110 hours, intravenous 115 hours
• Eliminated through urine

32. Adverse effects
• Headache, dizziness, paresthesia
• Somnolence, disturbance in attention
• Dysgeusia, dry mouth, diarrhea, oral hypoesthesia
• Vomiting, hot flush, anxiety, restlessness
• Palpitations, tachycardia, photophobia and arthralgia
• there is no specific antidote or effective method of hemodialysis for
Isavuconazole

33. • Treatment with the checkpoint inhibitor Nivolumab and Interferon-Υ
for an immunocompetent patient with extensive abdominal
Mucormycosis unresponsive to conventional therapy