Drug and Poison Information Center

Department of Pharmacy Practice

JSS College of Pharmacy
(A Constituent College of JSS Academy of Higher Education &Research, Mysuru)
Udhagamandalam - 643001
The Nilgiris

Drug and Poison Information Center

Query: Explain the signs and symptoms ,etiology and treatment options for the disease
condition mucormycosis

ANSWER :
Mucormycosis (previously called zygomycosis) is a serious but rare fungal infection caused by a group of
molds called mucormycetes. These molds live throughout the environment. Mucormycosis mainly affects
people who have health problems or take medicines that lower the body’s ability to fight germs and sickness. It
most commonly affects the sinuses or the lungs after inhaling fungal spores from the air. It can also occur on the
skin after a cut, burn, or other type of skin injury.
ETIOLOGY
Common
o Rhizopus spp.
o ~70% of rhinocerebral mucormycosis cases
o Mucor spp.
o Rhizomucor spp.
Rare
o Apophysomyces spp.
o Cunninghamella spp.
o Lichtheimia (Absidia) spp.
o Saksenaea spp.
CLINICAL PRESENTATION
o Unilateral headache - behind the eye
o Facial pain
o Eye swelling (Proptosis) + visual disturbance
o Necrotic lesions on the hard palate or nasal mucosa
o ENT symptoms
o Nasal congestion
o Black discharge
o Acute sinusitis
o Epistaxis
o Systemic symptoms: fevers

TREATMENT
Approach to treatment — Treatment of mucormycosis involves a combination of surgical debridement of
involved tissues and antifungal therapy. Elimination of predisposing factors for infection, such as
hyperglycemia, metabolic acidosis, deferoxamine administration, immunosuppressive drugs, and neutropenia, is
also critical.Intravenous (IV) amphotericin B (lipid formulation) is the drug of choice for initial
therapy. Posaconazole or isavuconazole is used as step-down therapy for patients who have responded to
amphotericin B. Posaconazole or isavuconazole can also be used as salvage therapy for patients who don't
respond to or cannot tolerate amphotericin B; for salvage therapy, the decision to use oral or IV posaconazole or
isavuconazole depends on how ill the patient is, whether an initial course of amphotericin B was able to be
administered, and whether the patient has a functioning gastrointestinal (GI) tract.
Surgery — Aggressive surgical debridement of involved tissues should be considered as soon as the diagnosis
of any form of mucormycosis is suspected. Surgical intervention with removal of necrotic tissue and debulking
infection has been associated with improved survival in anecdotal clinical reviews of rhinocerebral and
pulmonary infection. In the case of rhinocerebral infection, debridement to remove all necrotic tissue can often
be disfiguring, requiring removal of the palate, nasal cartilage, and the orbit. However, more recent experience
shows that endoscopic debridement with limited tissue removal can be accomplished. There are reports of
patients with early pulmonary infection who were cured with lobectomies. However, many patients present with
extensive involvement not amenable to complete resection and/or profound thrombocytopenia, which precludes
surgery. In these cases, every effort should be made to reverse immunosuppression, optimize underlying
medical conditions, and promptly administer antifungals.
Antifungal drugs — Early initiation of antifungal therapy improves the outcome of infection
withmucormycosis. Posaconazole has been mainly studied salvage therapy.
There are no randomized trials assessing the efficacy of antifungal regimens for mucormycosis because the
disease is rare.
Initial therapy — As noted above, amphotericin B is the drug of choice for initial therapy; most clinicians use
a lipid formulation of amphotericin B (rather than amphotericin B deoxycholate) in order to deliver a high dose
with less nephrotoxicity. The usual starting dose is 5 mg/kg daily of liposomal amphotericin B or amphotericin B
lipid complex, and many clinicians will increase the dose as high as 10 mg/kg daily in an attempt to control this
infection. The total dosage of lipid amphotericin B that should be administered has not been studied.

There are anecdotal reports of using combination therapy with amphotericin B and either posaconazole or an
echinocandin. However, there are no convincing data to support any form of combination therapy, and
combination therapy is not recommended in the major treatment guidelines.
There have been apparent cures of isolated renal mucormycosis using amphotericin B deoxycholate alone or
combined with nephrectomy . If nephrectomy is not performed, amphotericin B deoxycholate is the agent of
choice for initial therapy as the lipid formulations of amphotericin B do not penetrate the kidney or achieve
measurable concentrations in the urine.There is little experience using posaconazole or isavuconazole for this
indication. In severe cases in which there is little residual renal function, nephrectomy with a short course of
antifungal therapy (using an amphotericin B formulation, posaconazole, or isavuconazole) for two weeks
appears to be a reasonable course of action.
Step-down therapy — Posaconazole and isavuconazole are broad-spectrum azoles that are active in vitro
against the agents of mucormycosis and that are available in both parenteral and oral formulations. For patients
who have responded to a lipid formulation of amphotericin B, posaconazole or isavuconazole can be used for
oral step-down therapy. We continue amphotericin B until the patient has shown signs of improvement; this
usually takes several weeks.
When switching to oral posaconazole, we favor the use of posaconazole delayed-release tablets (300 mg every
12 hours on the first day, then 300 mg once daily) taken with food if possible. We do not use the oral
suspension of posaconazole since it is not highly bioavailable and requires fatty food for absorption. A serum
trough concentration of posaconazole should be checked after one week of therapy; we suggest a goal trough
concentration >1 mcg/mL, but higher levels are preferred for treatment of this serious infection
Salvage therapy — We use posaconazole or isavuconazole as salvage therapy for patients who do not respond
to or cannot tolerate amphotericin B . The IV formulation of posaconazole or isavuconazole should be used in
patients who have to be switched from amphotericin B before they have had a favorable response and in
patients who have an inability to absorb oral medications.
Posaconazole (both IV and delayed-release formulations) is given as a loading dose of 300 mg every 12 hours
on the first day, followed by a maintenance dose of 300 mg every 24 hours thereafter. The IV formulation
should be avoided in patients with moderate or severe renal impairment (creatinine clearance <50 mL/minute)
due to the potential for accumulation of the betadex sulfobutyl ether sodium (SBECD) vehicle, unless an
assessment of the possible benefits and risks to the patient justifies its use. If it is used in patients with renal
impairment, serum creatinine should be monitored closely, and, if increases occur, consideration should be
given to changing to the extended-release tablet formulation of posaconazole or to IV or oral isavuconazole. In
patients who are able to take medications orally, we use posaconazole delayed-release tablets, usually given
with food, rather than the oral suspension because bioavailability with the tablets is much better and it is easier
for patients to take.
Isavuconazole should be given as a loading dose of 200 mg IV or orally every 8 hours for the first six doses
followed by 200 mg IV or orally every 24 hours thereafter. Because the IV formulation of isavuconazole is
highly water soluble and does not contain the SBECD vehicle, there are no known concerns about administering
the IV formulation to patients with renal impairment.

Reference
 UpToDate [Internet]. Uptodate.com. 2021 [cited 25 June 2021]. Available from:
https://www.uptodate.com/contents/mucormycosis-zygomycosis
 Mucormycosis | Fungal Diseases | CDC [Internet]. Cdc.gov. 2021 [cited 25 June 2021]. Available from:
https://www.cdc.gov/fungal/diseases/mucormycosis/index.html
 Mucormycosis (Zygomycosis) Treatment & Management: Approach Considerations, Antifungal
Therapy, Surgical Intervention [Internet]. Emedicine.medscape.com. 2021 [cited 25 June 2021].
Available from: https://emedicine.medscape.com/article/222551-treatment