Mucormycosis and its management focusing more on the rhino orbito maxillary type as it is the area of interest for oral and macillofacial surgeons.

1. MUCORMYCOSIS
BY
DR.PRATHIBA SENTHIL KUMAR
DEPT OF ORAL AND MAXILLOFACIAL SURGERY
AJIDS

2. INTRODCUTION
• Mucormycosis is an aggressive, angioinvasive fungal
infection, caused by filamentous fungi that afflicts
immunocompromised patients with severe metabolic
conditions, such as uncontrolled diabetes mellitus.
• The first documented report of human mucormycosis is
credited to Paltauf, who in 1885 reported a disseminated
infection in a patient with rhinocerebral involvement caused
by angioinvasive, ribbon-like hyphae that they termed
Mycosis mucorina.

4. MICROBIOLOGY
• Rhizopus spp. (47%) were the most
frequently reported
• followed by Mucor spp. (18%),
• Cunninghamella bertholletiae (7%),
• Apophysomyces elegans (5%),
• Lichtheimia (Absidia) spp.
• (5%), Saksenaea spp. (5%),
• and Rhizomucor pusillus (4%),
• with a variety of other uncommon species
representing the remaining 8% of culture
Confirmed cases

5. MICROBIOLOGY
• The hyphae are broad (5 to 15 micron
diameter), irregularly branched, and have
rare septations.
• This is in contrast with the hyphae of
ascomycetous molds, such as Aspergillus,
which are narrower (2 to 5 micron
diameter), exhibit regular branching, and
have many septations.

6. Habitat
• The fungi can be commonly found in soil than in air
as these exist in the form of spores in order to
protect themselves as well as to assist the process of
dispersal.
• The occurrence thus is more prevalent in tropical
areas.
• The dispersal and occurrence of these species are
more common during summer than in winter as the
fungal spores thrive in dry and arid conditions.
• Besides, some of these fungi can also occur in
decaying matter like decaying vegetables and fruits.
• Mucoralean fungi usually reproduce anamorphically
via non-motile sporangiospores released from
different sporangia.

7. Routes of spread
• The primary mode of acquisition of mucormycosis is inhalation of spores from environmental sources.
• Trauma, penetrating wounds, burns, and direct injection of sporangiospores can cause infection through a cutaneous or
percutaneous route.
• Gastrointestinal (GI) mucormycosis, although less common, has been reported in both immunocompetent and
immunocompromised patients with repeated ingestion of spores during periods of severe malnutrition, ingestion of
nonnutritional substances (pica), ingestion of contaminated pharmaceutical products, prepackaged foods, fermented
porridges and alcoholic drinks prepared from corn, or eating with contaminated chopsticks.
• More recently, an outbreak of food poisoning was linked to intake of Greek yogurt contaminated with Mucor circinelloides.

8. Incidence before
and after covid

9. Predisposing
factors
 Diabetes mellitus, particularly with
ketoacidosis
 Immunosuppression due to treatment with
glucocorticoids,Solid organ transplantation
,AIDS etc
 Hematologic malignancies
 Treatment with deferoxamine
 Iron overload
 Trauma/burns
 Coronavirus disease 2019-associated

10. Covid associated mucormycosis • Iron starvation induces apoptosis in
rhizopus oryzae in vitro
• Fazal Shirazi,Dimitrios P Kontoyiann

11. • Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial Yeming Wang*, Dingyu Zhang*,
DEEP VEIN
THROMBOSIS ,
THROMBOEMBOLOISM
ETC.
COMPROMISED VASCULATURE –
PREDISPOSING FACTOR FOR
MUCORMYCOSIS

12. Pathogenesis

13. Mucorales appear to possess a unique mechanism
for adhering to and invading endothelial cells by
specific recognition of host receptor– glucose
regulator protein 78 (GRP78). Expression of
GRP78 on the endothelial cell surface increases as
a stress response after exposure to elevated
concentrations of β-hydroxy butyrate (BHB),
glucose, and iron, similar to those found in patients
with diabetic ketoacidosis

14. Diabletes mellitus
• Microenvironment in a diabetic patient is altered;
there are high levels of glucose, free iron, and ketone
bodies (BHB, B-hydroxy butyrate); and these
conditions cause stress on the endoplasmic reticulum
in the adjacent epithelial/endothelial cells.
• Rhizopus organisms have an enzyme, ketone
reductase, which allows them to thrive in high
glucose, acidic conditions.
• GRP78 is overexpressed and relocated in diverse
cellular compartments

15. Patients with diabetic ketoacidosis
are particularly susceptible to
developing rhinocerebral forms of
mucormycosis.

16. Iron overload
• It has been known for two decades that patients treated
with the iron chelator deferoxamine have a markedly
increased incidence of invasive mucormycosis.
• Fungi can acquire iron from the host by using low-
molecular-weight iron chelators (siderophores) or high-
affinity iron permeases, such as ferrirhizoferrin.
• While deferoxamine is an iron chelator from the
perspective of the human host, Rhizopus spp. actually
utilize deferoxamine as a siderophore to supply
previously unavailable iron to the fungus.
• Rhizopus spp. can accumulate 8- and 40-foldgreater
amounts of iron supplied by deferoxamine than can
Aspergillus fumigatus and Candida albicans, respectively,
and this increased iron uptake by Rhizopus spp. is
linearly correlated with its growth in serum.

17. Types of mucormycosis
RHINOORBITOCEREBRAl pulmonary
Cutaneous Gastrointestinal
Disseminated

18. Clinical presentation
of rhinoorbitocerebral
mucormycosis
1. Rhinosinusitis
2. Rhino-orbital
3. Rhinomaxillary
4. Rhinocerebral

19. Facial findings:
• Facial swelling
• A black eschar, which results from necrosis of
tissues after vascular invasion by the fungus,
may be visible in the nasal mucosa, palate, or
skin overlying the orbit
• Excutiating pain
• Paresthesia
• Sinus tract on face
• Infection in dangerous area of face

20. Intraoral findings:
• Halitosis
• Intraoral pus discharge
• palatal eschar
• Exposed palatal bone
• Sinus tract
• UNEXPLAINED Loosening of teeth
• Unhealed tooth socket
• Mobility of maxilla

21. Nasal findings:
• Perinasal swelling
• Foul smelling nasal discharge
• Nasal congestion
• Sinusitis
• destruction of the turbinates,
• black necrotic eschar in nasal cavity

22. Orbital findings
• Invasion of the orbit is typically unilateral
• Peri orbital cellulitis
• Chemosis
• Exophthalmos(Proptosis)
• Opthalmoplegia
• Erythema and cyanosis of the facial skin overlying the
involved sinuses and/or orbit
• Orbital apex syndrome
• Pain and blurring or loss of vision often indicate
invasion of the globe or optic nerve.

23. Proposed staging in rhino-orbito-cerebral mucormycosis

24. Cerebral
• SEVERE Headache, may be unilateral
• Cranial nerve involvement
• Rapidly progressive neurological deficit
• Intracranial complications include epidural
and subdural abscesses cavernous, and,less
commonly, sagittal sinus thrombosis.
• Frank meningitis in patients with
mucormycosis is rare.
• Comatose states
• Death

25. Pulmonary mucormycosis
• Refractory fever on broad-spectrum antibiotics
• Nonproductive cough,
• Progressive dyspnea
• Pleuritic chest pain.
• Pulmonary mucormycosis can traverse tissue planes in
the lung invading through thebronchi, diaphragm, chest
wall, and pleura.
• A pleural friction rub
• cavitation or potentially fatal hemoptysis.

26. Gastrointestinal
mucormycosis

27. Cutaneous mucormycosis

28. Diagnosis
Lab parameters: CBC/ ESR/ FBS, PPBS, HbA1C/ LFT/
RFT with electrolytes/ HIV, HbsAg / CSF (if indicated)
Culture and KOH mounting
Nasal endoscopy
Biopsy
IMAGING

29. Nasal endoscopy

30. Biopsy

31. CULTURE
• To confirm the diagnosis, biopsy samples can
be cultured.[
• All Mucorales grow rapidly (3–5 days) on
most fungal culture media, such as Sabouraud
agar and potato dextrose agar incubated at 25–
30°C

32. HISTOPATHOLOGY
Ribbon-like hyphae which branch at 90°
Hyphae in blood vessel
Mature sporangium of a Mucor[38

33. KOH MOUNT TEST
• Potassium hydroxide (KOH) preparation is used for the
rapid detection of fungal elements in clinical specimens,
as it clears the specimen making fungal elements more
visible during direct microscopic examination.
• KOH is a strong alkali.
• When specimen such as skin, hair, nails or sputum is
mixed with 20% w/v KOH, it softens, digests and clears
the tissues (e.g., keratin present in skins) surrounding
the fungi so that the hyphae and conidia (spores) of
fungi can be seen under a microscope.

35. MOLECULAR
ASSAYS
• If a histopathology study is positive for
infection, but a fungal culture is negative, a
test called polymerase chain reaction or
PCR may be used.
• The test can identify tiny amounts of DNA
including genetic material of infectious
organisms like fungi.
• This test is not widely available and has not
undergone clinical evaluation as to its
effectiveness or appropriateness for
diagnosing mucormycosis.

36. • Serum tests, such as the 1,3-beta-D-glucan assay and
the Aspergillus galactomannan assay, are being used with increased
frequency in patients suspected of having an invasive fungal infection.
• The agents of mucormycosis do not share these cell wall components and
neither test is positive in patients with mucormycosis.

37. Radiographic features
• RHINOROBITO CEREBRAL MUCORMYCOSIS

39. • T2 patterns in mucormycosis. T2 MRI showing A.
Heterogeneous pattern involving the maxillary sinus
(yellow arrow). B. Isointense pattern involving the
maxillary sinus (blue arrow). C. Hyperintense pattern
involving the sphenoid sinus (white arrow).

41. Pulmonary
• Large nodules or consolidations with an associated
reverse halo sign or large perilesional ground-glass
halos are common in mucormycosis.
• Lesions tend to show a peripheral predominance, and a
perivascular ground-glass focus preceded nodular
lesions in some cases
• multifocal pneumonia pattern, and this pattern was
associated with a high mortality rate

42. GASTROINTESTINAL; MUCORMYCOSI

43. ISOLATED CEREBRAL
• MRI aspects of cerebral
mucormycosisAxial enhanced T1-weighted
image (A, magnification of the right
temporal lobe ×3) and coronal T2-weighted
images (B and C) revealed infiltrative T1
hypointense and T2 hyperintense lesion in
the right temporal lobe, with peripheral
serpiginous and radial strands enhancement
(arrowheads, A). There is slight mass effect
and edema. Note the right lateral sinus
thrombosis (arrow, B) and the fluid-filled
mastoid cells (arrow, C).

44. Treatemnt
1.Rapidity of
diagnosis
2.Reversal of the
underlying
predisposing
factors (if possible)
3. Appropriate
surgical
debridement of
infected tissue
4.Appropriate
antifungal therapy

45. Management of Mucormycosis
•Arunaloke Chakrabarti &
•Shreya Singh

46. Medical
management
• Recommendation on antifungal therapy in Covid
associated mucormycosis when antifungal drug
availability is limited
• Antifungal prophylaxis is not recommended
• Start calculated dose of amphotericin B from first
day, avoid dose escalation
• Fluconazole, voriconazole, echinocandins
(caspofungin, anidulafungin, micafungin) or 5
flurocytosine is not active against mucormycosis
• Combination of antifungal therapy is generally not
recommended, as there is little evidence in support
of combination therapy

49. Inj Amphotericin B Deoxycholate(C-AmB):
Dose: 1.0-1.5 mg/kg once per day, IV:
infused over 4 - 6 hours
Half-life: Biphasic: Initial 15 to 48 hr,
Terminal 15 days
Disadvantages:
Highly toxic, Poor CNS penetration
To avoid infusion-related immediate
reactions, premedicate with: 1. NSAID
and/or diphenhydramine or
acetaminophen with diphenhydramine or
hydrocortisone 2. Pre-infusion
administration of 500 to 1,000 mL of
normal saline
Dosing: 1) Renal Impairment: Daily total
dose can be decreased by 50% or the
dose can be given every other day-
Haemodialysis or CRRT. 2) Hepatic
Impairment: No dosage adjustment

50. ADVERSE EFFECTS
• Hypersensitivity: Anaphylaxis, Infusion reactions
• Cardiovascular: Hypotension
• Central nervous system: Chills, malaise, pain & headache (less frequent with I.T.)
• Endocrine & metabolic: Hypokalemia, hypomagnesemia
• Gastrointestinal: Anorexia, diarrhoea, epigastric pain, heartburn, nausea (less frequent with I.T.), stomach cramps,
vomiting (less frequent with I.T.)
• Hematologic & oncologic: Anemia (normochromic-normocytic)
• Local: Pain at injection site (with or without phlebitis/ thrombophlebitis –incidence may increase with peripheral infusion
of admixtures)
• Renal: Renal function abnormality (including azotemia, renal tubular acidosis, nephrocalcinosis [>0.1 mg/ml]), renal
insufficiency
• Miscellaneous: Fever 1% to 10%:
• Genitourinary: Urinary retention

51. • Watch for: Urine output , Renal function Test (pH, Bl. Urea, S. Creatinine, Electrolytes)
• 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

52. Liposomal amphotericin B
Liposomal amphotericin B
(AmBisome®; LAmB) is a unique
lipid formulation of
amphotericin B that has been
used for nearly 20 years to treat
a broad range of fungal
infections.
While the antifungal activity of
amphotericin B is retained
following its incorporation into
a liposome bilayer, its toxicity is
significantly reduced

54. FESS
• The purpose of functional endoscopic sinus
surgery (FESS) is to restore normal paranasal air
sinuses mucociliary function

55. Types
Nasal endoscopy and uncinectomy with or
without aggernasi cell exenteration.
Type 1
Nasal endoscopy, uncinectomy, bulla
ethmoidectomy, removal of sinus lateralis
mucous membrane and exposure of frontal
recess/frontal sinus
Type 2
Type II plus maxillary sinus antrostomy through
the natural sinus ostium.
Type 3
Type III surgical technique with complete
posterior ethmoidectomy.
Type 4
Type IV surgical technique with sphenoidectomy
and stripping of mucous membrane
Type 5

56. SURGERY
Surgical debridement
• In rhinosinusitis surgical debridement of infected
tissue is a crucial component of therapy and should
be urgently performed to limit the aggressive spread
of infection to contiguous structures.
• Repeated removal of necrotic tissue or radical surgical
resection (e.g., exenteration of the orbit) with
subsequent reconstructive surgeries may be required for
lifesaving control of rapidly evolving infection.
• Extraction of tooth , thorough debridement and
curettage .

57. MAXILLECTOMY
• A maxillectomy is a procedure
to remove a primary tumor in the
maxilla. The procedure involves
surgical removal of some of the
bone, part of roof of mouth
possible some of the teeth.

62. Orbital
exentration
The scoring system is based on 3 main criteria, namely:
1. Clinical signs and symptoms
2. Direct and Indirect Ophthalmoscopy
3. Imaging
Based on the scoring system, it was observed that
those patients who crossed a score of 23 were
eligible candidates for orbital exenteration as
agreed upon by the Otorhinolaryngologist and
Ophthalmologists

64. Osteomyelitis

67. References
• Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases
• Cornely OA al: ESCMID and ECMM joint clinical guidelines for the diagnosis and management of
mucormycosis 2013.Clin Microbiol Infect 20(S3):5, 2014
• Spellberg B et al: Novel Perspective on mucormycosis: Pathophysiology, Presentation, and management.
Clin Microbiol Rev 18:556, 2005
• Mucormycosis uptodate ,Gary M Cox
• Treatment Protocol For Mucormycosis In Adult Patients- By Expert Committee of Civil Hospital, Ahmedabad
• Recommendation on antifungal therapy in Covid associated mucormycosis when antifungal drug availability
is limited : Fungal Infection Study Forum (FISF)

68. References
• A multicenter observational study on the epidemiology, risk factors, management and outcomes of mucormycosis in
India Atul Patel, MD, FIDSA
• Imaging features of rhinocerebral mucormycosis: A study of 43 patients JacobTherakathu ShaileshPrabhu
• Icmr guidelines for management of mucormycosis at the time of covid 19 pandemic
• Ho J, Fowler P, Heidari A, Johnson RH. Intrathecal Amphotericin B: A 60-Year Experience in Treating Coccidioidal
Meningitis. Clin Infect Dis. 2017 Feb 15;64(4):519-524. doi: 10.1093/cid/ciw794. PMID: 27927853.
• Brown JS, Rogers SN, McNally DN, Boyle M. A modified classification for the maxillectomy defect. Head Neck.

69. References
• Brown JS, Shaw RJ. Reconstruction of the maxilla and midface: introducing a new classification.
Lancet Oncol. 2010
• Shah K, Dave V, Bradoo R, Shinde C, Prathibha M. Orbital Exenteration in Rhino-Orbito-Cerebral
Mucormycosis: A Prospective Analytical Study with Scoring System. Indian J Otolaryngol Head Neck
Surg. 2019
• Farmakiotis D, Kontoyiannis DP. Mucormycoses. Infect Dis Clin North Am. 2016 Mar;30(1):143-63.
doi: 10.1016/j.idc.2015.10.011. PMID: 26897065.

70. Thank you