ENT-mucormycosis in brief intro, types, clinical presentation, treatment.

2.  Life threating infection caused by fungi of the order Mucorales.
 (recently these fungi are reclassified into mucorales from what was previously
called as zygomycetes)

3.  Incidence of mucormycosis seems to be on rise
 For decades the fatality rate remains to be >40% despite the aggressive surgical
and medical management
 In patients with haematological malignancy it is further more 60-90%

4.  Mode of spread- inhalation or inoculation of the sporangiospores in the skin or
mucosa
 Mucormyces is ubiquitous
 Some studies found seasonal incidence – more in autumn
 In developed country found to occur only in immunocompromised state
 In developing country – sporadic, more common in uncontrolled diabetes and
trauma

5.  Organ or hemopoietic stem cell transplant
 Neutropenia
 Malignancy
 DM with or without ketoacidosis
 Iron overload
 Major trauma
 Prolonged use of corticosteroids
 Intravenous drug abuse
 Malnourished

6.  AML has the highest risk for mucormycosis – 1%-8%
 In patients with stem cell transplant – 0.9%-2.0% (highest incidence among
patients developing graft versus host response)

7.  Predisposing factor in 36-88% cases
 Data from a study in a tertiary care center in India were also alarming, as 74% of
patients with mucormycosis had uncontrolled diabetes; in 43% of these cases,
diabetes was diagnosed for the first time.
 Chakrabarti A, Das A, Mandal J, et al. The rising trend of invasive mucormycosis
in patients with uncontrolled diabetes mellitus. Med Mycol 2006; 44:335–42.

8.  With prolonged use of steroids the immunosuppression would occur, also steroid
induced diabetes
 In cases with prolonged use of steroid in SLE- increased incidence was noted and
disseminated type of mucormycosis was more common
 Mortality is high 80%

9.  Therapy with DFO an iron chelator used to treat iron and aluminium over load in
dialysis reported is a risk factor for angioinvasive mucormycosis
 Most common form of Mucormycosis was disseminated form (44%)
 Mortality was 80%

10.  Widesoread use for aspergillus infection in patients with HM and Stem cell
transplant recipients

11.  Mucormycosis patients with HIV and AIDS is rare

12.  Hallmark of mucormycosis is tissue necrosis which results from the angioinvasive
and thrombotic character
 Based in clinical manifestation and anatomic site predilection 6 types of
mucormycosis are described

13.  Rhinocerebral 39%
 Pulmonary 24%
 Cutaneous 19%
 Disseminated 23%
 Gastrointestinal
 Rare variants- endocarditis, osteomyelitis, peritonitis, renal infection.

14.  In patients with neutropenia seen patient on induction chemotherapy, HSCT and
graft versus host reaction
 Mortality 76%.
 Symptomatically non specific.
 Patients present with prolonged high grade fever that is unresponsive to broad
spectrum antibiotics.
 Non productive cough

15.  On chest images are also non specific and indistinguishable from those of
pulmonary aspergillosis.
 Infiltration, nodules, cavitations, atelectasis, effusion, posterior tracheal banding
thickening, hilar or mediastinal lymphadenopathy.
 CT- reverse halo sign- focal round area of ground glass attenuation surrounded by
ring of consolidation.

16.  Most common type in Diabetes Mellitus.
 Inhalation of sporangiospore into the sinuses
 Rapidly spread to adjacent structures
 Cerebral vascular invasion- dissemination of disease.

17.  The fungus invades the cranium through the orbital apex or cribriform plate of
ethmoid bone and ultimately kills the host.
 Initial symptoms of RCOM are consistent with those of sinusitis and periorbital
cellulitis and include eye or facial pain and facial numbness followed by blurry
vision.

18.  In susceptible patients with multiple cranial nerve palsies, unilateral periorbital
facial pain, orbital inflammation, lid edema, blepharoptosis, acute ocular motility
changes, internal or external ophthalmoplegia, head ache and acute vision loss.
 Black necrotic eschar is the hallmark
 However the absence of this finding should not exclude the possibility of
mucormycosis.

19.  Fever is variable
 Total counts will be typically high.
 Preoperatively CECT is helpful in defining the extent of the ROCM
 CT shows- fluid filled ethmoid sinuses, and destruction of periorbital tissues and
bone margins.

20.  MRI is useful in identifying the intradural and Intracranial extent of ROCM
 Contrast enhanced MRI can identify the perineural spread
 Diagnosis of ROCM is always after histopathological evidence of fungal tissue
invasion.

21.  Direct inoculation of fungal spores in the skin, which may lead to disseminated
disease.
 Localised infection when it involves only the skin or the subcutaneous tissue.
 Deep infection- invades muscle and tendons or bones.
 Disseminated – involves non contiguous organs.

22.  Gradual and slowly progressive
 Fulminant leading to gangrene and hematogenous spread
 Necrotic eschar accompanied by surrounding erythema and induration.

23.  Rare
 Mortality is as high as 85%
 Only 25% of the cases are diagnosed antmortem.
 Mainly seen in premature neonates, malnourished children and individuals with
HMs
 Acquired by ingestion

24.  Stomach is the most commonly affected
 Fungus can invade bowel walls and blood vessels, resulting in bowel perforation,
peritonitis, sepsis and massive gastrointestinal haemorrhage- which most
common cause of death.

25. Spreads hematogenously to other organs
Most commonly associated with pulmonic variant
Iron overload, profound immunosuppression or profound neutropenia and active
leukemia.
Metastasis skin lesion is an important hallmark in early diagnosis.
Mostly fatal.

26.  4 IMPORTANT STEPS
1. Early diagnosis
2. Reversal of underlying predisposing factor
3. Surgical debridement where applicable
4. Prompt antifungal treatment

27.  A recent study from Chamilos et al. Quantified the benefit of early initiation of
polyene antifungal therapy. They reported that if treatment was initiated within 5
days of diagnosis of mucormycosis, survival was markedly improved compared to
initiation of polyene therapy at ≥6 days after diagnosis (83% vs 49% survival).

29.  Newer developmet – still under trials – PCR for diagnosis of mucormycosis
 CT- simple sinusitis – absence of deeper spread doesn’t rule out mucormycosis
 MRI- MORE SENSITIVE than CT scan for detecting orbital and cerebral spread

30.  Underlying disease should be controlled
 If patient is on prolonged steroids- reduce the dosage.
 Aggressive management of DM with control of acid base balance

31.  Blood vessels thrombosis with necrosis results in poor penetration of the
antifungal agents to the site of infection
 Surgery was independently found to be associated with good prognosis
 Roden MM, Zaoutis TE, Buchanan WL, et al.: Epidemiology and outcome of zygomycosis: a review of
929 reported cases. Clin Infect Dis 2005, 41:634–653
 Recent studies support the use of frozen section for clearance of margin
 Use of calcofluor florescence has shown to increase the sensitivity

32.  Primary antifungal is polyene
 Lipid formula of amphotericin is less nephrotoxic thus can be used in higher
dosage
 Associated with 67% survival rate compared with 39% in non liposomal
preparation
 LAmph is found to be more effective in CNS, DM, neutropenic cases

33.  Optimal dosage of polyenes
 Amphotericin- 1mg/kg/day
 Liposomal AmP- 5-7.5mg/kg/day

34.  Fluconazole, voriconazole, itraconazole do not have reliable activity against
mucormycosis.
 Sun QN, Fothergill AW, McCarthy DI, et al.: In vitro activities of posaconazole,
itraconazole, voriconazole, amphotericin B, and fluconazole against 37 clinical
isolates of zygomycetes. Antimicrob Agents Chemother 2002, 46:1581–1582.

35.  MIC is 1µg/ml.
 The dosage is 400mg bid- with variable bioavailability
 In pre- clinical animal models – ineffective for mucormycosis

36.  Recent studies showed that the combination therapy with polyene- caspofungin
was associated with improved outcomes in patients with rhino-ocular and
rhinocerebellar mucormycosis.
 Combination of Posaconazole with AmP didn’t show any added benefit