mucormycosis.pptx

 Mucormycosis is a general term for a group of uncommon infections cause by a
fungus (fungal infection).
 These infections are usually acquired when spores from the molds are breathed in
(inhaled) or, less commonly, enter the body through a cut in the skin.
 Mucormycosis is an aggressive, life-threatening infection that occurs in people
whose immune system doesn’t function well (immune-compromised) including
people with uncontrolled diabetes mellitus, people who have low levels of
neutrophils, a type of white blood cell that helps the body fight off infection and
heal itself (neutropenia), or people whose immune system is being suppressed by
medications (immunosuppression) as part of their treatment for blood cancer
(hematological malignancy), hematopoietic stem cell transplantation, or solid-organ
transplant.
 The infection is not contagious; it cannot be spread from one person to another.
Prompt diagnosis and early treatment are critical.
 Treatment usually consists of antifungal medications and surgery.

 Mode of spread- inhalation or inoculation of the sporangiospores in the skin or
mucosa.
 It is ubiquitous.
 Some studies found seasonal incidence- more in autumn.
 In developed country- only in immunocompromised state.
 In developing country- sporadic, more common in uncontrolled diabetes and trauma.
 However, incidence of mucormycosis seems to be on rise.
 For decades the fatility rate remains to be >40% despite of the aggressive surgical
and medical management.
 In patients with haematological malignancy, it is >60-90%

 The term mucormycosis is frequently used interchangeably with zygomycosis.
 The latter term referred to infections caused by fungi of the former phylum
Zygomycota (comprising Mucorales, Entomophthorales, and others), which became
obsolete with phylogenetic reanalysis of the kingdom Fungi.
 Today, mucormycosis describes infections caused by fungi of the order Mucorales.
The most frequently reported pathogens in mucormycosis are:
 Rhizopus (47%), Mucor (18%), and Rhizomucor (4%);
 Uncommon: Cunninghamella (7%), Absidia (5%), Saksenea (5%), and Apophysomyces
(5%)

 Rhino-Orbito-cerebral (sinus and brain)-mucormycosis is an infection in the
sinuses that can spread to the brain. This form of mucormycosis is most common in
people with uncontrolled diabetes and in people who have had a kidney transplant.
 Pulmonary (lung) mucormycosis is the most common type of mucormycosis in
people with cancer and in people who have had an organ transplant or a stem cell
transplant.
 Gastrointestinal mucormycosis is more common among young children than adults,
especially premature and low birth weight infants less than 1 month of age, who
have had antibiotics, surgery, or medications that lower the body’s ability to fight
germs and sickness.
 Cutaneous (skin) mucormycosis: occurs after the fungi enter the body through a
break in the skin (for example, after surgery, a burn, or other type of skin trauma).
This is the most common form of mucormycosis among people who do not have
weakened immune systems.
 Disseminated mucormycosis occurs when the infection spreads through the
bloodstream to affect another part of the body. The infection most commonly
affects the brain, but also can affect other organs such as the spleen, heart, and
skin.
 Isolated renal- cases in india and china

Cutaneous (skin) mucormycosis
Rhino-Orbito-cerebral mucormycosis

 Diabetes, especially with diabetic ketoacidosis
 Cancer
 Organ transplant
 Stem cell transplant
 Neutropenia (low number of white blood cells)
 Long-term corticosteroid use
 Injection drug use
 Too much iron in the body (iron overload or hemochromatosis)
 Skin injury due to surgery, burns, or wounds
 Prematurity and low birthweight (for neonatal gastrointestinal mucormycosis)

Symptoms of rhinocerebral (sinus and brain) mucormycosis include: One-sided
facial swelling, Headache, Nasal or sinus congestion, Black lesions on nasal bridge or upper
inside of mouth that quickly become more severe, Fever
Symptoms of pulmonary (lung) mucormycosis include: Fever, non-productive Cough,
Chest pain, Shortness of breath
Cutaneous (skin) mucormycosis can look like blisters or ulcers, and the infected area
may turn black. Other symptoms include pain, warmth, excessive redness, or swelling around
a wound.
Symptoms of gastrointestinal mucormycosis include: Abdominal pain, Nausea and
vomiting, Gastrointestinal bleeding
Disseminated mucormycosis typically occurs in people who are already sick from other
medical conditions, so it can be difficult to know which symptoms are related to
mucormycosis. Patients with disseminated infection in the brain can develop mental status
changes or coma.

 Healthcare providers consider your medical history, symptoms, physical
examinations, and laboratory tests when diagnosing mucormycosis.
 Healthcare providers who suspect that you have mucormycosis in your lungs or
sinuses might collect a sample of fluid from your respiratory system to send to a
laboratory.
 Your healthcare provider may perform a tissue biopsy, in which a small sample of
affected tissue is analyzed in a laboratory for evidence of mucormycosis under a
microscope or in a fungal culture.
 You may also need imaging tests such as a CT scan of your lungs, sinuses, or other
parts of your body, depending on the location of the suspected infection.

Reverse halo- sign
Thick wall cavitory lesions

 Specific serologic markers are currently not available.
 Use of galactomannan to exclude mucormycosis is moderately recommended.
 Certain rhizopus species yield positive BDG results.
 ELISA and LFIA able to detect.

 4 IMPORTANT STEPS
 Early diagnosis
 Reversal of underlying presdisposing factor
 Surgical debriment where applicable
 Prompt antifungal treatment
Diabetic ketoacidosis requires insulin and volume repletion with intravenous fluids.
Neutropenia associated with hematologic malignancy and its treatment should be
reversed, if possible, with the use of colony-stimulating factors and the withdrawal
of cytotoxic chemotherapy.
Wean glucocorticosteroids and other immunosuppressive drugs.
Interrupt deferoxamine therapy; hydroxypyridine chelating agents may be
substituted for deferoxamine

 In current practice, amphotericin B and isavuconazole are the two antifungal agents
licensed by the US Food and Drug Administration (FDA) for the primary therapy of
mucormycosis.
 First-line treatment- amphotericin derivative, preferably the liposomal form of
amphotericin B to minimize nephrotoxicity. Other options include amphotericin B
deoxycholate, isavuconazole, and posaconazole.
 COMBINATION THERAPY ADVANTAGES- More rapid fungicidal activity and lower risk of
resistance.
 DISADVANTAGES- Risk for antagonism, additive or synergistic toxicity, more drug-
drug interactions, and higher cost.
 Liposomal and lipid complex amphotericin B- 5 mg/kg/d up to 7.5-10 mg/kg/d to
treat mucormycosis.
 higher doses, however, has been associated with rates of nephrotoxicity up to 40%
without a concomitant mortality benefit. CNS disease.

 Amphotericin B deoxycholate
 used to treat mucormycosis, particularly when other formulations prove too costly.
 The typical dose is 1-1.5 mg/kg/d. The total dose given over the course of therapy
is usually 2.5-3 g. High 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.
 In addition, careful monitoring and repletion of serum electrolytes (eg, potassium,
phosphorus, magnesium) should be performed when administering any formulation
of amphotericin B

 Isavuconazole
 A novel triazole antifungal agent that was approved for the treatment of mucormycosis
in March 2015.
 The prodrug isavuconazonium sulfate is rapidly metabolized by serum
butylcholinesterase to the active form, isavuconazole (ISZ)
 Initial dosing is isavuconazonium sulfate 372 mg (isavuconazole 200 mg) every 8 hours
for 6 doses, followed by maintenance with 372 mg once daily.
 Advantages over other triazoles
 wider spectrum of antifungal activity.
 Excellent oral bioavailability not reliant on food intake or gastric pH and is also available
in an intravenous formulation, which does not contain the nephrotoxic solubilizing agent
cyclodextrin.
 Switching between oral and IV forms does not require dose adjustment.
 ISZ displays linear and predictable pharmacokinetics with minimal CYP3A4 interactions,
reducing or eliminating the need for therapeutic drug monitoring.
 Unlike voriconazole, ISZ does not cause phototoxicity, increased risk of squamous cell
carcinoma, or visual disturbance.

 Posaconazole
 Another triazole antifungal, has been shown to be superior to fluconazole or
itraconazole as prophylaxis against invasive mold infection (both aspergillosis and
mucormycosis) in patients with hematologic malignancy who have neutropenia or
GVHD.
 Used for off-label salvage treatment of mucormycosis in patients intolerant to
amphotericin B.
 FORMS AVAILABLE- oral suspension, delayed-release tablet, an intravenous
formulation is also available.
 300-mg tablet twice on day 1 followed by 300 mg orally once daily with or without
food.
 Rickerts et al reported that liposomal amphotericin B plus posaconazole was
successful in the treatment of disseminated mucormycosis in a patient who could
not undergo surgery
 Also been used as step-down therapy after the initial administration and control of
the disease with liposomal amphotericin B.

 Debridement of necrotic tissue in combination
with medical therapy is mandatory for patient
survival.
 For rhinocerebral mucormycosis
 surgical care includes drainage of the sinuses
and may require excision of the orbital contents
and involved brain. Repeated surgery may be
required.
 Excise pulmonary lesions if they are localized to
a single lobe.
 Excise cutaneous lesions entirely, and resect any
GI masses.

 Hyperbaric oxygen therapy after surgical
debridement has been used, especially in
cases of cutaneous disease and rhinocerebral
disease in diabetics.
 High oxygen concentrations may improve
neutrophil function, inhibit the growth of
Mucorales, and improve wound healing.
 Colony-stimulating factors have been used to
enhance immune responses, specifically in
neutropenic patients, as have interferon-
gamma and white blood cell transfusions
 iron chelators without xenosiderophore
activity (eg, deferasirox)
 Newer agents such as deferasirox were
hypothesized to decrease the risk of
mucormycosis via iron starvation

 Ongoing clinical surveillance and diagnostic imaging are required to ensure complete
resolution of mucormycosis and to detect relapse.
 The duration of therapy is highly individualized.
 Successful courses of amphotericin B typically last 4-6 weeks.
 Primary or salvage isavuconazole therapy may be continued for several months given
its higher tolerability compared with amphotericin.
 Repeated surgical debridement of necrotic tissue identified by follow-up head
computed tomography (CT) scan or magnetic resonance imaging (MRI) is often
indicated.
 For patients who successfully complete therapy for mucormycosis and who
subsequently require immunosuppressive treatments (eg, chemotherapy in a patient
with cancer), whether daily oral posaconazole or isavuconazole should be given as
secondary prophylaxis against disease relapse is unknown.

Pediatric Mucormycosis
 Underlying comorbidities such as hyperglycemia, acidosis in diabetic patients,
nutritional problems, neutropenia, lymphopenia, and immunosuppression must be
addressed.
 The drug of choice for treating mucormycosis is amphotericin B, with a dosage of 1-
1.5 mg/kg/d. Liposomal amphotericin B at dosages higher than these have also been
used to treat disseminated disease. Some authors have suggested doses as high as
10-15 mg/kg. A term neonate who was diagnosed with facial mucormycosis after
liver and small bowel transplantation survived after wide excision and 26 weeks of
treatment with liposomal amphotericin B.
 Azoles (eg, fluconazole, itraconazole) are not helpful in the treatment of
mucormycosis. Among relatively new triazoles, posaconazole is effective against
mucormycosis. This agent has an oral formulation and undergoes liver metabolism.
Posaconazole may be effective compared with other azoles against molds, including
mucormycosis. Studies are being conducted to evaluate combination antifungal
therapies.

 Hyperbaric oxygen has been noted to reduce the morbidity and mortality when
given in combination with medical and surgical therapy, with a 50% survival rate.
 Surgical debridement should be undertaken early in the course of the illness,
especially in cases of rhinocerebral mucormycosis. Instilling amphotericin B into
abscess cavities after debridement has been suggested. Repeat surgery may be
necessary to effectively eliminate all necrotic tissue in patients who survive.
Reconstructive surgery is inevitable for those who have disfigurement due to severe
rhinocerebral mucormycosis.

 Protect yourself from the environment. It’s important to note that although these
actions are recommended, they haven’t been proven to prevent mucormycosis.
 Try to avoid areas with a lot of dust like construction or excavation sites. If you can’t avoid
these areas, wear an N95 respirator (a type of face mask) while you’re there. Avoid direct
contact with water-damaged buildings and flood water after hurricanes and natural
disasters.
 Avoid activities that involve close contact to soil or dust, such as yard work or gardening. If
this isn’t possible,
 Wear shoes, long pants, and a long-sleeved shirt when doing outdoor activities such as gardening,
yard work, or visiting wooded areas.
 Wear gloves when handling materials such as soil or manure.
 To reduce the chances of developing a skin infection, clean skin injuries well with soap and water,
especially if they have been exposed to soil or dust.
 Antifungal medication. If you are at high risk for developing mucormycosis (for
example, if you’ve had an organ transplant or a stem cell transplant), your
healthcare provider may prescribe medication to prevent mucormycosis and other
mold infections. Doctors and scientists are still learning about which transplant
patients are at highest risk and how to best prevent fungal infections.

 Global guideline for the diagnosis and management of mucormycosis: an initiative of
the European Confederation of Medical Mycology in cooperation with the Mycoses
Study Group Education and Research Consortium
 Medscape
 CDC

mucormycosis.pptx

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