PULMONARY MUCORMYCOSIS

Dr. V. Gopala Krishnaiah

Professor & H.O.D of Pulmonology
BHASKAR MEDICAL COLLEGE
BACKGROUND
MM refers to rare, severe
opportunistic infection with fungi of
the order Mucorales.
Hence the name mucormycosis
ORGANISMS
Rhizopus species are the most common
causative organisms.
Other less frequent species include:
Rhizomucor,
Absidia,
Cunninghamella,
Saksenaea, and
Apophysomyces
PATHOPHYSIOLOGY
Mucorales fungi are ubiquitous
environmental organisms.
Humans are resistant to disease, but
immuno-compromised hosts are at risk.
The major route of infection is by inhalation
of spores.
Ingestion or traumatic inoculation are
recorded
PATHOPHYSIOLOGYcont.
Once the spores begin to grow, fungal
hyphae invade blood vessels, producing
tissue infarction, massive necrosis with bone
destruction.
Thus producing the life-threatening,
invasive, rhinocerebral, and other organ-
centered manifestations.
RISK FACTORS
Diabetes mellitus esp. with ketoacidosis
Neutropenea, HIV patients
Malnourished individuals, especially children
Desferoxamine therapy and all causes of iron overload
Burn victims susceptible to cutaneous MM
Steroid therapy
Hematologic and solid malignancies
BM transplant recipients
Persons in Renal Failure
Intravenous drug abusers (at risk for cerebral MM)
FREQUENCY
MM is extremely rare,one center showed it was
present in 0.7% of patients at autopsy.
Rhinocerebral disease is the most common form,
hence the name Zygomycosis.
Others include pulmonary, cutaneous,
gastrointestinal, and disseminated diseases.
Very rare cases occur in immuno-competent
patients, usually after traumatic inoculation.
AGE
MM is found in patients of a wide age range.
SEX
There is equal sex distribution, but
pulmonary MM shows a male-to-female
ratio of 3:1
MORTALITY/ MORBIDITY
Mucormycosis has a very high mortality rate
reaching 50 to 80% even with treatment.
Pulmonary and gastrointestinal diseases have
higher mortality rate due to late diagnosis.
Rhinocerebral disease causes significant
morbidity in patients who survive because
treatment requires extensive facial surgery.
CLINICAL PICTURE
Mucormycosis is
distinguished by its
fulminant course
with evidence of extensive
tissue necrosis.
PULMONARY MUCORMYCOSIS
Presents nonspecifically with fever,
dyspnea, cough and haemoptysis.
By comparison, signs of pulmonary and GI
MM are nonspecific, which leads to difficulty
in diagnosis.
BIOPSY
Pathognomonic
picture of broad,
irregular,
nonseptate, right-
angled,
branching
hyphae are
demonstrated by
H&E or fungal
stains.
Vascular invasion is
characteristic with
neutrophil infiltrate
BIOPSY
MM: HIGH
POWER
Histopathology
TREATMENT
1. MEDICAL CARE
A.Correction of the underlying
abnormality:
Diabetic ketoacidosis requires insulin & correction of acidosis
Neutropenia requires use of CSF and withdrawal of cytotoxic
CH
Wean glucocorticosteroids
Interrupt desferoxamine
B. Prompt institution of IV amphotericin
B therapy is critical to survival.
Amphotericin B
Is the only antifungal agent with proven
efficacy in mucormycosis.
The lipid formulations of amphotericin B
allows for very high doses while protecting
renal function.
High doses are required, and nephrotoxicity
may result.
2. POSACONAZOLE
In the form of Syrup for Oral Therapy.
In pulmonary disease, excise lesions if they are
localized to a single lobe.
3. SURGICAL CARE cont.
Finally, mucormycosis carries an
extremely poor prognosis.
Because of the rapidity with which
this disease progresses, prompt
diagnosis and aggressive therapy
are essential.
Palate
Orbital Mucormycosis
Cavernous Sinus
Male 60 yrs.
Occupation Farmer.
Presented with high-grade fever with chills for
the last 15 days.
Persistent cough with scanty mucoid sputum.
Breathlessness Grade III for the last 3 days.
Scanty urine with burning micturation for the
last 2 days.
Vomiting for the last 2 days, two episodes.
Generalized weakness.

Known case of systemic hypertension on Losar
25 mg twice daily.
Diabetes mellitus type II on oral Hypoglycemic
drugs.
No history of bronchial asthma.
Vitals:
Temp. 100 F
Pulse Rate 120 per min.
B.P 120/70 mmHg.
Respiratory Rate 24 per min.
SPO
2
100% with 2 liters of O
2
.


Lab Reports:
Total Leukocyte Count(TLC) 21,400
Cells per cumm.
ESR 118 mm first hour.
Serum Creatinine 2.2 mgs.
Serum sodium 121 mmol/L.
X-ray chest PA view Right upper lobe
consolidation.

On admission:
Haemoglobin 11.2 gms.
Total Leukocyte Count 15,300 cells per cumm.
After 5 days 9,560 cells.
Platelet 3,64,000.
Random Blood Sugar 331 mgs. 09:00 AM.
- 543 mgs 01:00 PM.
Blood Urea 96 mgs.
Serum Creatinine 2.5 mgs. 1
st
day of admission
-1.2 mgs. After 5 days.


1
st
Day 2
nd
Day 4
th
Day
Serum Sodium 126 mmol/L 128 mmol/L 134 mmol/L
Serum Potassium
3.1 mmol/L

3.7 mmol/L

3.3 mmol/L

Serum Chloride 96 mmol/L 100 mmol/L 110 mmol/L
LFT :
Total Bilirubin 0.6 mg.
ALT 35
AST 43
Alkaline phosphatase 88
Total proteins 5.6 grams.
Albumin 2.2 grams.
Globulin 3.4 grams.
A/G Ration 0.6

CT Scan of the Chest:
Right upper lobe consolidation with
cavity.
Ultrasound abdomen Normal study.
Sputum per AFB Negative.
Sputum per Gramstain Gram positive
cocci in pairs and short chains.
Sputum per culture and sensitivity
Sterile.

Bronchoscopy:
Right upper lobe mass lesion, pedunculated
with mucus plug bleeding on touch.

Bronchial washings, brushings, and biopsy
taken from right upper lobe bronchus mass
lesion

Sent for AFB Smear, Fungal elements,
Cytology and Histopathological examination
which reveals plenty of pus cell with few
lymphocytes; Sheet of epitheloid cells seen in
one area, No evidence of Caseation or
Langhans giant cells; No malignant cells;
AFB Negative; No Fungal Elements seen.
HISTOPATHOLOGY REPORT
MATERIAL : Bronchial Biopsy for HPE.
GROSS DESCRIPTION: Received four
pieces of gray whit soft tissue varying in
size from 2 to 4 mm. All embedded in one.
MIRCOSCOPIC EXAMINATION:
Section of biopsy tissue show bronchial
mucosa, lined by columnar epithelium and
few lobules of cortilagenous tissue.
There are multiple fungal colonies,
consisting of broad fungal hyphae with
perpendicular branching and no septation.
They are admixed with fibrinous material
and collections of neutrophils. No definite
stromal infiltration is seen.

HISTOPATHOLOGY REPORT (Continued)
HISTOCHEMISTRY: PAS STAIN show
positive staining of the fungal elements.
They are short, broad, filamentous and
show thick cell walls, without septations.

IMPRESSION: FEATURES ARE
SUGGESTIVE OF FUNGAL BAL,
BROCHUS. FEATURES ARE IN FAVOUR
OF MUCORMYCOSIS. ADVISED
FUNGAL CULTURE FOR
CONFIRMATION OF THE SPECIES.

TREATMENT
ANTIFUNGAL THERAPY
Liposomal and lipid complex amphotericin
B
Amphotericin B has proven efficacy in the
treatment of mucormycosis.
Liposomal formulation (e.g, AmBisoome) is the
drugh of choice based on efficacy and safety.
Lipid preparations of amphotericin B are used at 5
mg/kg/d.
Liposomal amphotericin B is amphotericin B
encapuslate in a bilayer of liposomes.

TREATMENT (CONT)
Amphotericin B
Amphotericin B is produced by strain of
Sterptomyces nodosus and can be fungistatic or
fungicidal.
Amphotericin B binds to sterols (e.g, ergosterol) in
the fungal cell membrane causing intracellular
components to leak, with subsequent fungal cell
death.
Amphotericin B deoxycholate can also be used for
the treatment of mucormycosis, especially in settings
of cost restraints.
The typical doses of this drug are required, and
nephrotoxicity may result.
Monitor the renal function of patients taking
amphotericin B; doubling of serum creatinine over
the baseline levels is an indication for changing to
liposomal amphotericin B.

TREATMENT (CONT)
Amphotericin B lipid complex (Abelcet)
Amphotericin B lipid complex is amphotericin
B in phospholipid complexed form.

This is an alternate therapy to liposomal
amphotericin B.

Installation of intrabrochial
amphotericin B lipid complex.
TREATMENT (CONT)
Posaconazole
Posaconazole, a triazole, is currently considered a
second-line drug for tratement of mucormycosis and
the typical dose is 400 mg twice daily (total of 800
mg/d).
Administration with a high-fat meal/food and acidic
beverages enhances absorption of the drug.
Patients on posaconazole should avoid antacids,
especially proton pump inhibitors.
Posaconazole has also been used as sequential
therapy after the initial administration and control of
the disease with liposomal amphotericine B.
Posaconazole is a triazole antifungal agent that blocks
ergosterol synthesis by inhibiting the enzyme
lanosterol 14-alpha-demethylase and sterol precursor
accumulation.
Posaconazole is available as an oral suspension (200
mg/5 mL).
TREATMENT (CONT)
Combined therapy
Pre-clinical and limited retrospective
clinical data suggest that combination
therapy with lipid formulations of
amphotericin and an echinocandin
improves survival during mucormycosis.

A definitive trial is needed to confirm these
results.
TREATMENT (CONT)
Other antifunal agents
Other azoles (e.g, fluconazole, voriconazole)
have not shown significant activity against
mucormycosis fungi.
Of note, despite the use of voriconazole
prophylaxis in high-risk patients (e.g,
transplant recipients)m], breakthrough
zygomucosis has been reported.

Surgical intervention
Debridement of necrotic tissue in combination
with medical therapy is mandatory for patient
survival.
Excise pulmonary lesions if they are localized
to a single lobe.
TREATMENT (CONT)
Adjunctive therapies
Hyperbaric oxygen therapy after surgical
debridement has been used, especially in case of
cutaneous disease and rhinocerebral disease in
diabetics.
High oxygen concentrations may improve
neutrophil function, inhibit the growth of Mucorales,
and improve wound healing.

Duration of therapy and long-term
monitoring
Successful courses of therapy typically last 4-6
weeks and require cumulative doses that are
equivalent to greater than 2 g of amphotericin B
deoxycholate.
Posaconazole offers another treatment option.
Prognosis
Rhinocerebral disease:
Mortality ~62%
Pulmonary disease:
Mortality ~76%, higher in severely
immunosuppressed.

Cutaneous:
Mortality ~10%