on 01-Dec-2022 (Thu)

Mucormycosis is manifested by a variety of different syndromes in humans, particularly in immunocompromised patients and those with diabetes mellitus [1]. Devastating rhino-orbital-cerebral and pulmonary infections are the most common syndromes caused by these fungi.

There is some controversy over the terminology used to refer to infections due to this group of fungi. The term "mucormycosis" was used for years and then was supplanted by "zygomycosis" for several decades. Based on molecular studies, "mucormycosis" is currently again the appropriate term [1-4].

The genera in the order Mucorales cause most human infection. These organisms are ubiquitous in nature and can be found on decaying vegetation and in the soil. These fungi grow rapidly and release large numbers of spores that can become airborne.

The genera most commonly found in human infections are Rhizopus, Mucor, and Rhizomucor; Cunninghamella, Absidia (now reclassified as Lichtheimia), Saksenaea, and Apophysomyces are genera that are less commonly implicated in infection [5].

The hyphae of the Mucorales are distinct and allow for a presumptive identification from clinical specimens. The hyphae are broad (5 to 15 micron diameter), irregularly branched, and have rare septations (picture 1). 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.

Rhizopus organisms have an enzyme, ketone reductase, which allows them to thrive in high glucose, acidic conditions. Serum from healthy individuals inhibits growth of Rhizopus, whereas serum from individuals in diabetic ketoacidosis stimulates growth [6].

Rhino-orbital-cerebral and pulmonary mucormycosis are acquired by the inhalation of spores. In healthy individuals, cilia transport these spores to the pharynx and they are cleared through the gastrointestinal tract. In susceptible individuals, infection usually begins in the nasal turbinates or the alveoli [7]. The agents of mucormycosis are angioinvasive; thus, infarction of infected tissues is a hallmark of invasive disease [8].

Deferoxamine, which chelates both iron and aluminum, increases the risk of mucormycosis by enhancing growth and pathogenicity [7,9-11]. The deferoxamine-iron chelate, called feroxamine, is a siderophore for the species Rhizopus, increasing iron uptake by the fungus, which stimulates fungal growth and leads to tissue invasion [8,12].

The majority of patients with deferoxamine-associated infection present with disseminated disease that is rapidly fatal, with a mortality rate that approaches 90 percent [11]

In contrast with deferoxamine, other iron chelating agents, such as deferasirox and deferiprone, do not act as siderophores and therefore do not increase the risk of mucormycosis.

Almost all patients with invasive mucormycosis have some underlying disease that both predisposes to the infection and influences the clinical presentation. The most common underlying diseases are [5,16-28]:

● Diabetes mellitus, particularly with ketoacidosis

● Treatment with glucocorticoids [23]

● Hematologic malignancies [1,25,29]

● Hematopoietic cell transplantation [5,23,30]

● Solid organ transplantation [30-33]

● Treatment with deferoxamine [9-11,13] (see 'Deferoxamine and iron overload' above and "Iron chelators: Choice of agent, dosing, and adverse effects")

● Iron overload [13]

● Recent coronavirus disease-2019 (COVID-19) infection [34-36]

● AIDS

● Injection drug use

● Trauma/burns [37-39]

● Malnutrition

A review of 929 cases of mucormycosis that were reported between 1940 and 2003 noted that diabetes mellitus was the most common risk factor, found in 36 percent of cases, followed by hematologic malignancies (17 percent) and solid organ or hematopoietic cell transplantation (12 percent) [5].

In some patients, mucormycosis was the diabetes-defining illness. In a later study of 101 patients diagnosed with mucormycosis between 2005 and 2007 in France, hematologic malignancy was the most common risk factor, occurring in 50 percent of patients, followed by diabetes in 23 percent and trauma in 18 percent of cases [ 37].

Among patients with malignancy, hematologic malignancies are much more frequently associated with mucormycosis than are solid tumors [5,23-25]. Pulmonary infection is more common than rhino-orbital-cerebral infection in this patient-population. However, even in patients with hematologic malignancies, mucormycosis appears to occur in less than 1 percent of patients [40].

A case-control study in a population of patients with hematologic malignancies compared patients with mucormycosis to those who had no fungal infection; voriconazole prophylaxis was an independent risk factor for mucormycosis (odds ratio 10.4, 95% CI 2.1-39) [25].

Although the possible causes of the increase in mucormycosis in patients with hematologic malignancies continue to be debated, reasons that have been proposed include selection of the agents of mucormycosis caused by voriconazole use, increasing use and intensity of immunosuppressive agents, and a decrease in invasive aspergillosis-related mortality following HCT, resulting in the emergence of rare fungi during the late post-transplant period [42].

Among solid organ transplant recipients, risk factors for mucormycosis include renal transplantation [31], renal failure, diabetes, and prior voriconazole or caspofungin use [33].

As noted above, diabetes is a common predisposing condition [5]. Diabetes appears to be more likely than other conditions to predispose to rhino-orbital-cerebral infection, but the reason for this is unknown [44]

One hypothesis that has been suggested to explain the decline in the United States is the widespread use of statins, which have inhibitory activity in vitro against a wide range of the agents of mucormycosis [26].

Outbreaks and clusters have been associated with adhesive bandages, wooden tongue depressors, adjacent building construction, and hospital linens [46-50]. A survey found that Mucorales could be cultured from 47 percent of hospital linen at several cancer and transplant centers [51]

Cases of mucormycosis have occurred following a tornado, a tsunami, and a volcanic eruption [53-57]. As an example, in 2011, an outbreak of necrotizing soft tissue infections causes by Apophysomyces trapeziformis occurred in patients with traumatic injuries resulting from a tornado in Joplin, Missouri, in the United States [53]. A total of 18 suspected cases were identified, of which 13 were confirmed. Two patients had diabetes and none were immunocompromised. Ten patients required intensive care unit admission and five died.

There have been numerous reports of mucormycosis in patients diagnosed with coronavirus disease 2019 (COVID-19) [34-36,59-62]. The majority involve individuals with underlying diabetes mellitus who received steroids for COVID-19 prior to diagnosis with mucormycosis. Most cases were detected two to three weeks after the initial diagnosis of COVID-19.

Rhino-orbital-cerebral mucormycosis is most frequently reported, and symptoms include facial pain, facial or orbital swelling, headache, and/or nasal eschar. Pulmonary mucormycosis infections have been identified in individuals with COVID-19 who develop unexplained worsening pulmonary status or complications. Gastrointestinal mucormycosis has been reported as well [36,63-65].

Reports suggest that onset of mucormycosis symptoms usually occurs 5 to 14 days after admission for COVID-19, but there are reports of individuals receiving both diagnoses at the time of presentation [66,67]. The majority of reports are from India, but cases have been reported from around the world. Overall mortality in case series from India ranges from 15 to 31 percent.

Mucormycosis is characterized by infarction and necrosis of host tissues that results from invasion of the vasculature by hyphae [27]. The pace is usually fast, but there are rare descriptions of infections with an indolent course [68,69].

Rhino-orbital-cerebral mucormycosis — The most common clinical presentation of mucormycosis is rhino-orbital-cerebral infection, which is presumed to start with inhalation of spores into the paranasal sinuses of a susceptible host. Hyperglycemia, usually with an associated metabolic acidosis, is the most common underlying condition [5]. A review of 179 cases of rhino-orbital-cerebral mucormycosis found that 126 (70 percent) of the patients had diabetes mellitus and that most had ketoacidosis at the time of presentation [16]. There are rare reports of rhino-orbital-cerebral mucormycosis in the absence of any apparent risk factors [16,69-72].

The infection usually presents as acute sinusitis with fever, nasal congestion, purulent nasal discharge, headache, and sinus pain. All of the sinuses become involved, and spread to contiguous structures, such as the palate, orbit, and brain, usually progresses rapidly over the course of a few days. However, there have been some reports of rhino-orbital-cerebral mucormycosis with an indolent course that progresses over the course of weeks [68].

The hallmarks of spread beyond the sinuses are tissue necrosis of the palate resulting in palatal eschars, destruction of the turbinates, perinasal swelling, and erythema and cyanosis of the facial skin overlying the involved sinuses and/or orbit (picture 2). 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 (picture 3) [73,74].

Signs of orbital involvement include periorbital edema, proptosis, and blindness. Facial numbness is frequent and results from infarction of sensory branches of the fifth cranial nerve. Spread of the infection from the ethmoid sinus to the frontal lobe results in obtundation. Spread from the sphenoid sinuses to the adjacent cavernous sinus can result in cranial nerve palsies, thrombosis of the sinus, and involvement of the carotid artery. Hematogenous spread to other organs is rare unless the patient has an underlying hematologic malignancy with neutropenia.

A review of 208 cases of rhino-orbital-cerebral mucormycosis published in the literature between 1970 and 1993 found the following frequency of symptoms and signs [75]:

● Fever – 44 percent

● Nasal ulceration or necrosis – 38 percent

● Periorbital or facial swelling – 34 percent

● Decreased vision – 30 percent

● Ophthalmoplegia – 29 percent

● Sinusitis – 26 percent

● Headache – 25 percent

Rhino-orbital-cerebral mucormycosis is most commonly caused by R. oryzae.

Pulmonary mucormycosis — Pulmonary mucormycosis is a rapidly progressive infection that occurs after inhalation of spores into the bronchioles and alveoli (image 1). Pneumonia with infarction and necrosis results, and the infection can spread to contiguous structures, such as the mediastinum and heart [76,77], or disseminate hematogenously to other organs [78,79].

Most patients have fever with hemoptysis that can sometimes be massive [78,79]. The most common underlying conditions have been hematologic malignancies, treatment with glucocorticoids or deferoxamine, and solid organ transplantation; pulmonary infection is less common than rhino-orbital-cerebral infection in diabetics [17,78-83]. In a series of 24 patients with mucormycosis and hematologic malignancy, 71 percent had pulmonary involvement and only one had rhino-orbital-cerebral involvement; 7 of 12 patients who underwent autopsy had disseminated disease in addition to pulmonary infection [23].

Gastrointestinal mucormycosis — Although unusual, mucormycosis of the gastrointestinal tract may occur as the result of ingestion of spores. One review of 87 cases found that the stomach was the most common site (58 percent), followed by the colon (32 percent) [84]. The ileum and esophagus were rare sites of involvement.

The underlying diseases of patients with gastrointestinal mucormycosis have been diabetes mellitus, solid organ transplantation, treatment with glucocorticoids, and prematurity and/or malnutrition in infants [18,84-87]. Patients present with abdominal pain and hematemesis. The gastrointestinal lesions are necrotic ulcers that can lead to perforation and peritonitis [18]. Bowel infarctions and hemorrhagic shock can result from gastrointestinal mucormycosis [88], and the prognosis for all patients is poor.

Cutaneous mucormycosis — Infection of the skin and soft tissues with the agents of mucormycosis usually results from inoculation of the spores into the dermis. Thus, cutaneous mucormycosis is almost always associated with trauma or wounds. The entry of the fungi into the dermis can result from seemingly innocuous insults, such as the entry site for an intravenous catheter, spider bites, and insulin injection sites [19,20,89-93]. Infection has also been associated with contaminated traumatic wounds, dressings and splints, burns, and surgical sites [19,20,46,53,54,56,58,89-93].

When infection is associated with relatively minor breaks in the skin, the host usually has some underlying disease, such as diabetes mellitus, organ transplantation, neutropenia, or severe prematurity. Infections associated with major trauma or contaminated dressings have been found in otherwise immunocompetent patients [5,93].

Cutaneous mucormycosis usually appears as a single, painful, indurated area of cellulitis that develops into an ecthyma-like lesion. Patients who have suffered trauma with an open wound that was contaminated with spores can develop rapidly progressive tissue necrosis, reflecting the presence of ischemic infarction [19,20,54,56,58,90,92,93]. Dissemination and deep tissue involvement are unusual complications of cutaneous mucormycosis [91,93].

Renal mucormycosis — Isolated involvement of the kidneys with mucormycosis has been reported and is presumed to occur via seeding of the kidneys during an episode of fungemia. Almost all patients with isolated renal mucormycosis have risk factors for fungemia, including an intravenous catheter, intravenous drug use, or AIDS [21,22,94-96].

Patients with renal mucormycosis usually present with flank pain and fever. Involvement can be either unilateral or bilateral.

Isolated CNS involvement — Central nervous system (CNS) mucormycosis typically arises from an adjacent paranasal sinus infection. However, there have been more than 30 cases of isolated CNS mucormycosis described in the literature [22,97-101]. Infection is thought to result from seeding of the brain during an episode of fungemia, analogous to renal involvement. Over two-thirds of the patients with isolated CNS mucormycosis have been people who inject intravenous drugs who presumably have injected material contaminated with fungi directly into the bloodstream. Some of the patients with isolated CNS mucormycosis have had HIV infection in addition to drug use [22,98,102]. However, it is not clear whether HIV infection is an independent risk factor.

Most of the patients with isolated CNS mucormycosis have presented with lethargy and focal neurologic deficits, with the vast majority having involvement of the basal ganglia [97-99]. Isolated involvement of the frontal lobe has also been described [97].

Disseminated disease — Disseminated mucormycosis is rare and occurs most commonly in severely immunocompromised patients, burn patients, premature infants, and individuals who have received deferoxamine [1,5]. In the series of 929 cases of mucormycosis described above, disseminated disease was present in 40 to 50 percent of patients with cerebral or pulmonary mucormycosis [5]. The mortality rate in patients with disseminated mucormycosis was 96 percent.

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.

Polymerase chain reaction (PCR)-based techniques performed on histologic specimens that show fungal elements can confirm the diagnosis of mucormycosis [103-105]. However, the value of these tests on histologic samples with no demonstrable fungal elements is unclear.

While there have been several studies showing the value of serum or plasma PCR tests, their utility in clinical practice is unclear [ 39,106-112], and their commercial availability remains limited. A positive test may influence the choice of antifungal (for example, changing from voriconazole to amphotericin B), but a negative test cannot rule out mucormycosis.

Rhino-orbital-cerebral infection — The presence of mucormycosis should be suspected in high-risk patients, especially those who have diabetes and metabolic acidosis and who present with sinusitis, altered mentation, and/or infarcted tissue in the nose or palate.

Endoscopic evaluation of the sinuses should be performed to look for tissue necrosis and to obtain specimens. The specimens should be inspected for characteristic broad, nonseptate hyphae with right-angle branching using calcofluor white and methenamine silver stains. The presence of the characteristic hyphae in a clinical specimen provides a presumptive diagnosis that should prompt further evaluation (picture 1). However, the absence of hyphae should not dissuade clinicians from the diagnosis of mucormycosis when the clinical picture is highly suggestive.

Further evaluation includes imaging to gauge sinus involvement and to evaluate contiguous structures such as the eyes and brain [116]. We generally perform a computed tomography (CT) scan as the initial imaging study as it can often be obtained quickly and is more sensitive than magnetic resonance imaging (MRI) for detecting bony erosions [117]. Clinicians should have a low threshold for performing an MRI in patients with abnormalities on CT because the MRI will enhance detection of intracranial, intraorbital, and cavernous sinus involvement.

Pulmonary infection — The diagnosis of pulmonary mucormycosis is difficult because the presentation does not differ from pneumonia due to other angioinvasive molds. Isolating an agent of mucormycosis from respiratory cultures in a high-risk patient with a compatible clinical presentation is an indication for starting empiric treatment.

Because obtaining tissue can be difficult in these cases, we often rely on radiographic evidence to support the diagnosis. Chest radiographs or CT scans can have variable findings:

● The most common abnormalities are focal consolidation, masses, pleural effusions, or multiple nodules [80,119]. The presence of a pleural effusion or more than 10 nodules may independently predict mucormycosis and help differentiate it from aspergillosis in immunocompromised individuals [119].

● A halo sign (ground-glass attenuation surrounding a nodule) is highly suggestive of angioinvasive fungi, including mucormycosis.

● Reversed halo signs (focal areas of ground-glass attenuation surrounded by a ring of consolidation) have been reported and may be more common in mucormycosis than other invasive mold infections [120-122]. In one study of 189 patients with fungal pneumonia, a reversed halo sign was seen in 7 of 37 patients with mucormycosis (19 percent), 1 of 132 patients with invasive aspergillosis (<1 percent), and none of 20 patients with fusariosis [120].

● Cavitary lesions with or without air crescent signs are unusual, although cavitation may be more common in COVID-19-associated mucormycosis [80,123].

Sputum or bronchoalveolar lavage (BAL) specimens can show the characteristic broad nonseptate hyphae, which is often the first indicator of mucormycosis [81]. However, in one case series, only 25 percent of sputum or BAL specimens were positive premortem [23]. Hyphae can also be demonstrated on lung biopsy (picture 1).

Other syndromes — The diagnosis of gastrointestinal mucormycosis can be made with endoscopic biopsy of the lesions that show the characteristic hyphae. For isolated renal involvement, percutaneous biopsy or nephrectomy can establish a diagnosis [21]. Urine cultures are almost always sterile. Imaging of the kidneys with CT can demonstrate either ill-defined areas of low attenuation and diminished enhancement suggestive of pyelonephritis or multiple small foci suggestive of abscesses.

In isolated central nervous system involvement, CT scan usually shows poorly enhancing lesions; cerebrospinal fluid cultures are negative. Diagnosis can be made with biopsy or resection of the involved areas.

Approach to treatment — Treatment of mucormycosis involves a combination of surgical debridement of involved tissues and antifungal therapy [2,28]. 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 [124,125]. 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 [126,127]. 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 [127].

Antifungal drugs — Early initiation of antifungal therapy improves the outcome of infection with mucormycosis. This was illustrated in a retrospective study of 70 patients with hematologic malignancy who had mucormycosis in which delayed amphotericin B therapy (starting treatment ≥6 days after diagnosis) resulted in an almost twofold increase in mortality at 12 weeks after diagnosis (83 versus 49 percent) [129].

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.

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 [130-133]. 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 [134]. 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 (see "Pharmacology of azoles", section on 'Posaconazole'). The data supporting the use of posaconazole for mucormycosis are discussed below.

When using isavuconazole, loading doses are necessary for the first 48 hours. Loading doses of 200 mg (ie, two capsules) of oral isavuconazole (equivalent to 372 mg of the prodrug isavuconazonium sulfate) should be given every 8 hours for six doses, followed by 200 mg orally once daily starting 12 to 24 hours after the last loading dose [135]. More detail regarding pharmacology of isavuconazole is found elsewhere. (See "Pharmacology of azoles", section on 'Isavuconazole' and "Pharmacology of azoles", section on 'Isavuconazole'.)

Salvage therapy — We use posaconazole or isavuconazole as salvage therapy for patients who do not respond to or cannot tolerate amphotericin B [134,135]. 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 (equivalent to 372 mg of the prodrug isavuconazonium sulfate) 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.

Duration of therapy — As noted above, patients can be switched from a lipid formulation of amphotericin B to delayed-release posaconazole or isavuconazole tablets for oral step-down therapy once a favorable clinical response has been achieved, which usually takes several weeks.

Therapy should continue until there is clinical resolution of the signs and symptoms of infection, as well as resolution of radiographic signs of active disease; therapy should also continue until reversal of underlying immunosuppression has been achieved, when feasible [138]. Therapy often extends for months, and some patients remain on therapy for life if immunosuppression cannot be corrected.

Combination antifungal therapy — As noted above, there are no convincing data to support any form of combination antifungal therapy, and combination therapy is not recommended in the major treatment guidelines. Larger studies are needed to establish whether combination therapy is beneficial [139].

Other antifungal agents, including voriconazole, fluconazole, and flucytosine, are not effective against the Mucorales [130,131,133,149,150].

Hyperbaric oxygen — Hyperbaric oxygen has been used in some patients with mucormycosis, but the benefit of this therapy has not been established [75,155,156].

Independent risk factors for mortality include disseminated infection, renal failure, and infection with Cunninghamella species, while the use of surgery and administration of any antifungal agent were associated with a better outcome [5].

Rhino-orbital-cerebral infection — A review of 208 patients with rhino-orbital-cerebral infection showed that the most significant factors associated with death were delayed diagnosis, the presence of hemiparesis/hemiplegia, bilateral sinus involvement, leukemia, renal disease, and treatment with deferoxamine [75].

Overall mortality from rhino-orbital-cerebral mucormycosis ranges from 25 to 62 percent, with the best prognosis in patients with infection confined to the sinuses [ 5,157]

Among COVID-19-associated cases, severe COVID-19 with need for mechanical ventilation appears to predict increased mortality [157].

Pulmonary mucormycosis — The outcome in patients with pulmonary mucormycosis is worse than for patients with rhino-orbital-cerebral involvement, with mortality rates as high as 87 percent [5,31,78]. This may be in part due to underlying conditions and the inability to widely excise the involved tissues. Widely disseminated mucormycosis carries a mortality rate of 90 to 100 percent [5].