1Scholar Student, Delight College of Pharmacy, Koregaon Bhima, Pune, Maharashtra, 412216.
2Department of Pharmaceutics, Assistant Professor, Delight College of Pharmacy, Koregaon Bhima, Pune, Maharashtra, 412216.
3Department of Pharmaceutical Quality Assurance, Assistant Professor, Delight College of Pharmacy, Koregaon Bhima, Pune, Maharashtra, 412216
Mucormycosis, a rare but life-threatening fungal infection, is caused by molds from the order Mucorales. This infection primarily affects immunocompromised individuals, such as those with diabetes, hematologic malignancies, or those undergoing organ transplantation. The clinical manifestations vary depending on the site of infection, with common forms including rhinocerebral, pulmonary, gastrointestinal, and cutaneous mucormycosis. Diagnosis is challenging, as there are no reliable circulating biomarkers. Definitive diagnosis relies on tissue sampling through biopsy or surgical debridement, with histopathological examination identifying broad, non-septate hyphae typical of Mucorales. Direct microscopic examination of fresh tissue, enhanced by optical brighteners and fluorescence microscopy, can aid in early diagnosis. Staining methods like Grocott methenamine silver (GMS) and periodic acid Schiff (PAS) are also helpful. Due to the invasive nature of brain biopsies and the potential for neurological damage, central nervous system mucormycosis is often diagnosed indirectly through identification of the pathogen in the sinuses or lungs. Early diagnosis and prompt antifungal treatment are crucial, as mucormycosis has a high mortality rate. Surgical debridement is often required alongside antifungal therapy. Prevention focuses on controlling risk factors such as blood glucose levels and optimizing immune function in at-risk patients.
Mucormycosis is a group of fungal infections caused by Zygomycetes, within the Mucorales order, and can occur in various forms, including rhino-orbitocerebral, pulmonary, gastrointestinal, cutaneous, and disseminated infections. Pulmonary mucormycosis is the second most frequent manifestation. This study examines the demographics, clinical features, diagnostic methods, radiologic findings, treatments, and outcomes associated with pulmonary mucormycosis. Mucormycosis is the second most common invasive fungal infection after aspergillosis, with an increasing incidence reported in certain countries. This term refers to diseases caused by filamentous fungi within the Mucorales order. People at higher risk include those with poorly controlled diabetes, immunocompromised individuals such as patients undergoing treatment for hematologic cancers or those receiving solid organ or hematopoietic stem cell transplants, as well as individuals who have suffered severe trauma to soft tissues, often with direct contamination of the wound by organic material. The clinical presentation of mucormycosis varies based on the host's immune status. For example, patients with diabetes typically develop rhino-orbital-cerebral mucormycosis (ROCM), while those with hematologic malignancies often present with sino-pulmonary disease. Trauma patients commonly develop necrotizing infections of the skin and soft tissues. Across all forms of mucormycosis, the infection is characterized by aggressive tissue destruction and infarction due to angioinvasion. Involvement of the central nervous system (CNS) is one of the most serious forms of the disease, often determining both survival and long-term outcomes for affected patients.
OBJECTIVE:
This study aims to characterize the demographics, clinical presentation, diagnostic methods, radiologic findings, treatment approaches, and outcomes of patients with pulmonary mucormycosis. Mucormycosis is an emerging, life-threatening fungal infection caused by Mucorales species. It predominantly affects immunocompromised individuals, particularly those with hematological malignancies, organ transplants, or diabetes mellitus. The most common forms of mucormycosis are rhino-orbito-cerebral and pulmonary. Interestingly, the location of the infection is often linked to the patient's underlying condition: pulmonary mucormycosis is more frequently seen in individuals with hematologic cancers, while rhino-orbito-cerebral mucormycosis is more commonly associated with diabetes. Cutaneous mucormycosis typically results from direct fungal inoculation following trauma or surgery. Gastrointestinal mucormycosis occurs after ingesting contaminated food or through the use of contaminated medical devices, affecting the stomach or colon. The disseminated formof the infection is the most severe, often seen in patients with significant immunosuppression. There are also rare presentations of mucormycosis affecting the heart (endocarditis), bones and joints (osteoarticular), or isolated cerebral infections. Healthcare-associated mucormycosis is a particular concern in premature newborns and burn unit patients. Clinical symptoms and CT scan findings are not highly specific, although the early appearance of a reversed halo sign is associated with pulmonary mucormycosis. A promising new diagnostic tool involves the detection of Mucorales DNA in the bloodstream, which could enhance early diagnosis and prompt treatment. Treatment should include antifungal therapy, addressing the underlying condition, and surgical intervention when appropriate.
Mucormycosis In Covid 19
Coronavirus Disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been linked to various opportunistic bacterial and fungal infections. Aspergillus and Candida are the primary fungal pathogens responsible for co-infections in COVID-19 patients. Recently, there has been a significant increase in cases of mucormycosis among people with COVID-19, particularly in India. The factors contributing to the growth of Mucorales spores in these patients include a combination of low oxygen levels (hypoxia), high blood glucose (due to diabetes, new-onset hyperglycemia, or steroid-induced hyperglycemia), acidic conditions (such as metabolic acidosis and diabetic ketoacidosis), elevated iron levels (high ferritin), and reduced white blood cell (WBC) function due to immunosuppression (from the SARS-CoV-2 virus, steroids, or underlying comorbidities). Additional risk factors include prolonged hospitalizations and mechanical ventilation. Mucormycosis, initially described as phycomycosis or zygomycosis in 1885 by Paltauf and later named by American pathologist Baker in 1957, is an aggressive infection caused by molds from the genera Rhizopus, Mucor, Rhizomucor, Cunninghamella, and Absidia of the Mucorales order. The most common species, Rhizopus oryzae, is responsible for approximately 60% of mucormycosis cases and accounts for 90% of rhino-orbital-cerebral mucormycosis (ROCM) cases. Infection occurs primarily through the inhalation of fungal spores.
An unusual outbreak of mucormycosis took place in India during the second wave of COVID-19 in the spring of 2021. COVID-19-associated mucormycosis (CAM), particularly rhino-orbital-cerebral mucormycosis (ROCM), was predominantly observed in patients with poorly controlled diabetes who had been treated with excessive doses of glucocorticoids.
Fig .1) Mucormycosis In Covid-19
Background Treatment Strategies For Mucormycosis
The effective treatment of mucormycosis requires four key steps: 1) early diagnosis, 2) addressing any underlying predisposing risk factors, 3) surgical debridement when necessary, and 4) prompt antifungal therapy.
Early Diagnosis
A study by Chamilosetal. demonstrated the significant benefit of initiating polyene antifungal therapy early. They found that starting treatment within 5 days of diagnosing mucormycosis significantly improved survival rates compared to beginning therapy after 6 days or more (83% vs. 49% survival). Therefore, early diagnosis is critical to ensure timely initiation of appropriate antifungal treatment. There is a pressing need for the development of more effective diagnostic methods. The creation of quantitative polymerase chain reaction (PCR) systems is an area of ongoing research, which could facilitate faster and more accurate diagnosis.
Imaging and Diagnostic Tools
In patients with rhino-orbital-cerebral mucormycosis, CT scans often only reveal sinusitis, meaning that the absence of deeper infection on a CT scan does not exclude mucormycosis. MRI scans, however, are more sensitive than CT scans for detecting orbital and central nervous system (CNS) involvement. For pulmonary mucormycosis, particularly in cancer patients, CT scans can be helpful in early detection. Logistic regression analysis has shown that pulmonary mucormycosis in cancer patients can be differentiated from aspergillosis based on the presence of sinusitis, multiple nodules on the CT scan, and pleural effusion.
Characteristics Of Mucormycosis
Clinical Manifestations
Invasive mucormycosis is characterized by rapid tissue necrosis due to vascular invasion and subsequent thrombosis. The disease can manifest in several forms, including rhino-orbital-cerebral, pulmonary, cutaneous, gastrointestinal, and disseminated mucormycosis. In a review of 929 mucormycosis patients between 1940 and 2003, diabetes was the most common underlying condition (36%). The clinical presentation varies depending on the host's health status. Patients with diabetes most commonly present with rhino-orbital-cerebral mucormycosis (66%), followed by pulmonary (16%) and cutaneous (10%) forms. In contrast, individuals without underlying conditions typically experience cutaneous mucormycosis (50%). Patients treated with deferoxamine more often present with pulmonary mucormycosis (28%), followed by rhino-orbital-cerebral (26%) and disseminated disease (23%). Among intravenous drug users, cerebral mucormycosis is the most common (62%), followed by cutaneous (11%) cases, while solid-organ transplant recipients most often present with pulmonary (37-53%) or rhino-orbital-cerebral disease (31%). Rhino-orbital-cerebral mucormycosis can begin as rhinosinusitis or sinusitis, evolving into rhino-orbital or rhinocerebral disease. Signs of disease progression include necrosis or black eschar in the nasal cavity or palate, as well as cranial nerve palsies (trigeminal or facial), ophthalmoplegia, and loss of vision. Intracranial complications, such as epidural and subdural abscesses, cavernous sinus thrombosis, and, less commonly, sagittal sinus thrombosis, may occur, although meningitis is rare.
Pulmonary mucormycosis typically presents with fever unresponsive to antibiotics, cough, pleuritic chest pain, and dyspnea. Vascular invasion can lead to fatal hemoptysis. Pulmonary mucormycosis and pulmonary aspergillosis often have similar clinical characteristics, but patients with leukemia and pulmonary aspergillosis are more likely to have concurrent sinusitis, a history of prophylactic voriconazole use, more than ten nodules, and pleural effusion on chest CT. The reverse halo sign may be an early radiographic indicator of pulmonary mucormycosis. Cutaneous mucormycosis is usually acquired through direct inoculation of fungal spores, burns, or traumatic wounds. The infection typically begins with erythema and skin induration, progressing to necrosis and the formation of a black eschar.
Gastrointestinal mucormycosis is rare and challenging to diagnose, with only 25% of cases being identified before death due to its nonspecific symptoms. Risk factors include severe malnutrition, premature birth, and immunosuppression. Neutropenic patients may present with fever, typhlitis, and hematochezia. Disseminated mucormycosis can affect multiple organs and is commonly reported in patients with cerebral (48%), cutaneous (39%), and pulmonary (20%) involvement.
METHODS:
We conducted a retrospective review of clinical data from 35 patients diagnosed with pulmonary mucormycosis between 2000 and 2015. The diagnosis was confirmed either by positive cultures from sterile sites or histopathological evidence of mucormycosis. Logistic regression was used to identify independent predictors of 28-day mortality, and survival was analyzed using the Kaplan-Meier method.
Type Of Mucormycosis
Rhino-orbital-cerebral mucormycosis (ROCM) is the most common clinical form of mucormycosis. The infection typically begins when fungal spores are inhaled, allowing the fungus to infect the paranasal sinuses. From there, the infection can rapidly spread to nearby structures, including the palate, sphenoid sinuses, orbits, cavernous sinuses, and eventually the brain. The development of tissue necrosis, often visible as a black eschar, is a concerning sign of the infection’s local progression. In a meta-analysis of 175 cases of rhino-orbital-cerebral mucormycosis (ROCM) published between 1994 and 2005, diabetes mellitus was the most common underlying condition, present in 64% of cases, followed by hematological malignancies (15%) and renal diseases (13%). In two separate studies, Rhizopus species were most commonly associated with the rhino-cerebral form of the disease. This observation may be attributed to differences in virulence among the various genera within the Mucorales order. Experimental studies have shown that ketoacidosis predisposes mice to infections caused by Rhizopus species but not Lichtheimia species. This could be related to the discovery that glucose-regulated protein 78 (GRP78), a chaperone protein induced by elevated glucose levels, serves as the host receptor for R. arrhizus in endothelial cells in mice. In a study of 22 patients with rhino-orbital-cerebral mucormycosis (ROCM), the most common presenting symptoms included unilateral facial pain (86%), multiple cranial nerve palsies (68%), periorbital edema (59%), fever (50%), and diplopia (41%). Three clinical signs were found to significantly impact survival, and their presence should trigger urgent treatment: chemosis, sixth cranial nerve palsy, and cognitive disturbances.
Differentiating ROCM from bacterial orbital cellulitis (BOC), which is much more common, is critical for preventing the infection from spreading to orbital and cerebral tissues. However, this can be challenging, as the early clinical signs of both conditions often overlap. A case-controlled study comparing 14 ROCM patients to 20 BOC patients found that extraocular muscle limitation was more common in ROCM cases, while eyelid swelling was more frequently observed in BOC patients.
2) Pulmonary Mucormycosis (PM)
Pulmonary mucormycosis (PM) is strongly associated with hematologic malignancies. Three recent studies from Europe, North America, and France have shown that hematologic malignancies are the most common underlying conditions in patients with PM, accounting for 51%, 70%, and 79% of cases, respectively. Similarly, the lungs are the most frequent site of mucormycosis in patients with hematologic malignancies, representing 34%, 43%, and 44% of cases in these studies. Additionally, pulmonary mucormycosis is the predominant form of the disease seen in solid organ transplant recipients. Among patients with hematologic malignancies, several key risk factors for mucormycosis have been identified. These include neutropenia (80%), corticosteroid use (26%), hematopoietic stem cell transplant (24%), diabetes (18%), and graft-versus-host disease (GVHD) (10%). The symptoms of pulmonary mucormycosis (PM) are nonspecific and typically include fever, cough, dyspnea, and chest pain. Lesions usually affect the pulmonary parenchyma but can extend to the chest wall, pulmonary arteries, aorta, mediastinum, or pericardium. Invasion of the pulmonary arteries can lead to hemoptysis. In a review of localized pulmonary mucormycosis, Lee et al. found that 97% of cases showed visible endobronchial changes, such as stenosis, mucosal erythema, airway obstruction, mucoid secretions, polypoid masses, and granulation tissue. Among patients with hematologic malignancies, several key risk factors for mucormycosis have been identified. These include neutropenia (80%), corticosteroid use (26%), hematopoietic stem cell transplant (24%), diabetes (18%), and graft-versus-host disease (GVHD) (10%). The symptoms of pulmonary mucormycosis (PM) are nonspecific and typically include fever, cough, dyspnea, and chest pain. Lesions usually affect the pulmonary parenchyma but can extend to the chest wall, pulmonary arteries, aorta, mediastinum, or pericardium. Invasion of the pulmonary arteries can lead to hemoptysis. In a review of localized pulmonary mucormycosis, Lee et al. found that 97% of cases showed visible endobronchial changes, such as stenosis, mucosal erythema, airway obstruction, mucoid secretions, polypoid masses, and granulation tissue. In patients with risk factors for pulmonary mucormycosis (PM), symptoms such as fever, cough, and chest pain should prompt an immediate high-resolution computed tomography (CT) scan. Although CT findings are not specific, they can suggest a fungal infection, with common features including nodules (with or without a halo sign or reverse halo sign), masses, cavitation, micronodules, and pleural effusion. Differentiating mucormycosis from invasive pulmonary aspergillosis (IPA) can be difficult, as both conditions share similar clinical and radiological features, as well as common risk factors. However, the reverse halo sign (RHS), which appears as a focal ground-glass opacity surrounded by a ring or crescent-shaped consolidation, is a radiological pattern that may indicate mucormycosis.
Fig 2) Pulmonary Mucormycosis
A. CT of a patient with PM showing atoll sign (arrow). B. Chest radiograph of the same patient showing right lower lobe lesion with air-fluid level (arrow). C.Fungal ball with air crescent sign (arrow) mimicking an aspergilloma. D. Cavitatory lesion (arrow) mimicking a malignancy. CT, computed tomography; PM, pulmonary mucormycosis.
3) Cutaneous Mucormycosis (CM)
Cutaneous mucormycosis occurs when fungal spores are directly inoculated into damaged skin, potentially leading to disseminated disease. However, dissemination from internal organs to the skin is extremely rare. In a review of 929 reported cases of mucormycosis, cutaneous involvement was the third most common site, affecting 19% of patients. While most cases were limited to the skin, 24% involved deep extension into bone or muscle. Hematogenous spread from the skin to other noncontiguous organs occurred in 20% of cases, whereas dissemination from other organs to the skin was observed in only 3%. A history of skin barrier disruption, such as trauma (40%), surgery (15%), use of dressings, or burns, was common among these patients. Cases of cutaneous mucormycosis have also been reported following natural disasters and blast injuries in combat situations. Post-traumatic mucormycosis was the third most common cause of mucormycosis in the French "RetroZygo" study (18%) and the second most common cause (17%) in a concurrent European study. Notably, it primarily affected immunocompetent patients, with 75% of patients having no underlying disease according to a literature review. The main forms of trauma leading to post-traumatic mucormycosis included traffic accidents (37%), domestic accidents (15%), and natural disasters (13%). The clinical presentation of cutaneous mucormycosis can vary. Typically, it begins with induration of the skin accompanied by erythema, which rapidly progresses to necrosis. However, in immunosuppressed patients, a nonspecific erythematous macule may be an early sign of disseminated disease. Common symptoms included necrosis (76%), redness (48%), swelling (43%), purulent discharge (23%), and a moldy appearance (22%). The main species isolated from these cases were Apophysomyces elegans, Lichtheimia, and Mucor species. In 41% of cases, Mucorales were associated with bacterial infections, which can delay the diagnosis of mucormycosis. Skin or wound biopsies should be performed routinely, as mucormycosis can be diagnosed easily through direct examination and culture.
4) Gastro-intestinal Mucormycosis
Primary gastrointestinal mucormycosis is the least common form of the infection. It can result from ingesting contaminated food, such as fermented milk or dried bread products, or from healthcare-associated contamination via devices. The stomach is the most frequently affected site, followed by the colon, small intestine, and esophagus. In a retrospective study of 31 cases, intestinal mucormycosis was the most common form (52%), followed by gastric disease (42%). The primary underlying conditions for gastrointestinal mucormycosis were solid organ transplantation (SOT) (52%) and hematologic malignancies (35%). This form of mucormycosis has also been reported in premature neonates. The most common presenting symptom was abdominal pain (68%), followed by gastrointestinal bleeding (48%) and changes in bowel habits (10%). Fever was observed in only 19% of cases. A larger proportion of patients with gastric mucormycosis were SOT recipients (11 out of 13), while intestinal mucormycosis was more common in patients with hematologic malignancies (12 out of 16). Diagnosis can often be suspected based on endoscopic findings, such as fungal masses or necrotic lesions overlying ulcerated areas, which can lead to perforation and peritonitis. The optimal treatment involves urgent surgical intervention combined with intravenous amphotericin B. However, due to the nonspecific nature of the symptoms, diagnosis is frequently delayed, and the mortality rate remains high at 57%.
5) Disseminated Mucormycosis
infection refers to an infection affecting at least two separate, non-contiguous Disseminated areas of the body. A prospective study conducted across 13 European countries from 2005 to 2007 found that 15% of patients had disseminated disease. The most commonly affected areas were the lungs, sinuses, soft tissues, central nervous system, liver, and kidneys. Individuals with iron overload, particularly those treated with deferoxamine, and those with severe immunosuppression—such as stem cell transplant recipients with graft-versus-host disease undergoing corticosteroid treatment or prolonged neutropenia are most at risk for developing disseminated mucormycosis. To diagnose disseminated mucormycosis, comprehensive imaging such as cerebral MRI and a sinus-thoraco-abdominal CT scan should be conducted. Patients with disseminated disease generally have a higher mortality rate compared to those with other clinical forms, with mortality ranging from 58% to 79%.
6) Health-Care Associated Mucormycosis (HCM)
Healthcare-associated mucormycosis (HCM) is a significant concern, particularly in neonatal care, hematology, transplant, and intensive care units, especially among burn patients. A review of 169 HCM cases from 1970 to 2008 identified several major underlying conditions, including solid organ transplantation (24%), diabetes (22%), and extreme prematurity (21%). Among transplant recipients, 60% developed mucormycosis due to graft transmission. Forty-one percent of the cases were linked to surgical site infections, with cardiovascular surgery being the most common procedure associated with HCM. Other outbreaks were clustered and tied to contaminated medical devices like adhesive bandages, wooden tongue depressors, and ostomy bags, as well as environmental sources such as water systems and nearby construction. More recent outbreaks have been connected to contaminated hospital linens. The skin was the most frequently affected area (57%), followed by the gastrointestinal tract (15%). Rhizopus was the most commonly identified fungal genus (43%), consistent with other forms of mucormycosis. Healthcare-associated mucormycosis (HCM) is a significant concern, particularly in neonatal care, hematology, transplant, and intensive care units, especially among burn patients. A review of 169 HCM cases from 1970 to 2008 identified several major underlying conditions, including solid organ transplantation (24%), diabetes (22%), and extreme prematurity (21%). Among transplant recipients, 60% developed mucormycosis due to graft transmission. Forty-one percent of the cases were linked to surgical site infections, with cardiovascular surgery being the most common procedure associated with HCM. Other outbreaks were clustered and tied to contaminated medical devices like adhesive bandages, wooden tongue depressors, and ostomy bags, as well as environmental sources such as water systems and nearby construction. More recent outbreaks have been connected to contaminated hospital linens. The skin was the most frequently affected area (57%), followed by the gastrointestinal tract (15%). Rhizopus was the most commonly identified fungal genus (43%), consistent with other forms of mucormycosis.
DIAGNOSIS
Currently, there are no clinically available circulating biomarkers for mucormycosis. As a result, a definitive diagnosis is based on microbiological analysis of tissue obtained through biopsy or surgical debridement. A presumptive diagnosis can be made by examining fresh tissue directly under a microscope. The sensitivity of direct microscopy is significantly improved when using optical brighteners, like Calcofluor white, and fluorescence microscopy. On direct microscopy, the presence of broad (6-16 micrometer), non-septate (or pauci-septate) hyphae with right-angle branching suggests a Mucorales infection, as opposed to Aspergillus species. The non-septate hyphae of Mucorales are more vulnerable to damage from shear stress, so tissue grinding may reduce the effectiveness of culture. Therefore, homogenizing tissue samples should be avoided when mucormycosis is suspected. Staining methods like Grocott methenamine silver (GMS) and periodic acid Schiff (PAS) can enhance the detection of Mucorales on histopathological examination. Mucorales may require longer staining durations than other fungal species. Since brain biopsies are invasive and carry the risk of neurological damage, CNS mucormycosis is often diagnosed indirectly by detecting the pathogen in the sinuses or lungs. Patients suspected of having rhinocerebral mucormycosis (ROCM) should be assessed by an experienced ENT surgeon. Fiberoptic examination of the nasal cavity and septum may reveal ischemic or necrotic lesions in the mucosa, which should be biopsied. Flexible bronchoscopy, bronchoalveolar lavage (BAL), or CT-guided lung biopsy are commonly used to diagnose pulmonary mucormycosis.
TREATMENT
Among 47 neutropenic patients (80%) who received oral antifungal prophylaxis during their condition, treatments included fluconazole (18 patients), itraconazole (15 patients), nystatin (8 patients), oral amphotericin B (4 patients), and ketoconazole (2 patients). The median duration of prophylaxis was 18 days (ranging from 5 to 90 days). These patients later developed fever and were treated empirically with broad-spectrum antibiotics (β-lactam plus aminoglycoside, with or without a glycopeptide), for a median of 10 days (ranging from 1 to 35 days). After a median of 90 hours of fever unresponsive to antibiotics, 49 patients (83%) received empirical antifungal treatment. Of these, 39 patients were given intravenous deoxycholate amphotericin B (AmB), with 12 of them also receiving oral azoles. The median daily dose of AmB was 1 mg/kg (with a total median dose of 1000 mg, ranging from 500 to 1200 mg). Six patients were treated with either fluconazole (3 cases) or itraconazole (3 cases) alone. Twelve patients received liposomal amphotericin B (L-AmB) at a median daily dose of 3 mg/kg (with a total median dose of 5000 mg, ranging from 2100 to 19,000 mg). In four cases, L-AmB was the first-line treatment, while in eight others, it replaced AmB due to issues such as renal impairment, drug intolerance, or failure of the initial AmB treatment. Seven patients underwent radical surgical procedures: two had eye enucleation, four had sinus debridements, and one underwent lung lobectomy.
MANAGEMENT
Early detection and rapid diagnosis are crucial in managing mucormycosis. While clinical signs and imaging may suggest the condition, obtaining tissue samples (for pathology and culture) as soon as possible is essential. Starting systemic antifungal treatment early directly influences patient outcomes, without affecting the diagnostic yield. Addressing underlying risk factors, like controlling blood sugar in diabetic patients, is also important. In cases where the risk factor can't be removed, such as in cancer patients or transplant recipients, reducing immunosuppressive therapy is critical. Persistent immunosuppression, like ongoing neutropenia, complicates treatment. Amphotericin B (AmB) is the most effective drug against Mucorales and is the preferred choice for initial treatment. Although AmB deoxycholate (AmBD) was the only available form for years, its use was limited by toxicity, particularly kidney damage and infusion reactions. Newer lipid formulations of AmB, like ABLC, ABCD, and L-AmB, were developed to reduce these side effects.Lipid formulations of Amphotericin B (AmB) enable prolonged treatment and higher daily doses with reduced toxicity. However, the optimal daily dosage for mucormycosis remains unclear. Typically, the dose is 5 mg/kg/day, but in severe cases, higher doses (7–10 mg/kg/day) may be used. Research suggests that using high-dose liposomal AmB (10 mg/kg/day) does not improve outcomes and can increase toxicity.
Among azole antifungals, posaconazole and isavuconazole are the most effective against Mucorales and are often used as step-down therapy after an initial response to AmB. They are also used as salvage therapy for patients who cannot tolerate AmB. Mucorales are resistant to other azoles (fluconazole, itraconazole, and voriconazole), echinocandins, and flucytosine. Posaconazole, available in various formulations, has shown activity against Mucorales. Two studies have examined oral suspension posaconazole as salvage therapy in patients with invasive mucormycosis. One study, involving 24 patients, found a favorable response in 79% of cases, but the varying endpoints make the results difficult to interpret. The second study, a retrospective review of 91 patients, reported a 60% success rate at 12 weeks. Both studies used the oral suspension form, which has absorption issues and requires multiple daily doses with fatty foods or supplements.
CONCLUSION
Pulmonary mucormycosis typically presents as rapidly progressing, often fatal pneumonia in patients with hematologic malignancies, diabetes, or those who have undergone organ transplants. However, diabetic patients may experience a more indolent course with a better prognosis. Diagnosing pulmonary mucormycosis is challenging when relying on sputum, needle aspirates, or bronchoalveolar lavage cultures. Although cytological diagnosis is possible, a definitive diagnosis usually requires histologic identification of the organism in the affected tissues. Early diagnosis through invasive biopsy techniques and prompt surgical intervention can help reduce mortality. Radiological findings in pulmonary mucormycosis are nonspecific and may include progressive lobar or multilobar consolidation, pulmonary masses, and nodules. Cavitation occurs in up to 40% of cases, but the air-crescent sign is rare. CT scans may reveal findings that lead to changes in management or diagnostic approach in up to 26% of cases. Mucormycosis is a developing invasive fungal infection that requires prompt and accurate clinical diagnosis to improve survival outcomes. When available, molecular diagnostic tests should be utilized to speed up the process. The primary treatment involves a combination of amphotericin B and surgery, with second-generation azole derivatives also being an option. Managing underlying health conditions is also a critical part of the treatment plan. In recent years, several new treatment options for mucormycosis have emerged. Lipid formulations of amphotericin B are now the preferred first-line treatment, with liposomal amphotericin being particularly favored for central nervous system infections. The potential for combining lipid amphotericin B with echinocandins or an iron-chelation strategy is an area that warrants further research. For salvage therapy, options include posaconazole, deferasirox, adjunctive cytokine therapy, and hyperbaric oxygen. Successful antifungal treatment depends on addressing underlying host factors that predispose to infection, performing surgical debridement of necrotic tissue when possible, and ensuring an early diagnosis to enable prompt initiation of antifungal therapy.
REFERENCE
Mahesh Nalawade*, Anil Panchal, Vishal Madankar, A Review on: Mucormycosis -from the Pathogens to the Disease, Int. J. Sci. R. Tech., 2025, 2 (3), 375-384. https://doi.org/10.5281/zenodo.15067873
10.5281/zenodo.15067873
