Role of granulocyte colony-stimulating factor in the treatment of mucormycosis

Several problems in the management of life-threatening mucormycosis remain unresolved, necessitating new methods of management. Four patients with histopathologically proven rhinocerebral mucormycosis were treated with high cumulative doses of granulocyte colony-stimulating factor (G-CSF). All had multiple predisposing factors for mucormycosis, particularly leukemia and neutropenia. Two patients refractory to fluconazole therapy were treated with liposomal amphotericin B. The improvement in clinical manifestations was closely related to neutrophil recovery, and all patients were alive at the end of therapy. In addition to surgical debridement and antifungal therapy, G-CSF seems to have played a role in their survival.     

Paranasal sinus mucormycosis in an immunocompetent host: efficacy and safety of combination therapy with Liposomal Amphotericin B and adjuvant rHuGM-CSF

Invasive mucormycosis is a well-documented disease in the immunocompromised patient, but in recent years it has been reported increasingly in immunocompetent patients. We report a case of maxillary paranasal sinus mucormycosis in an immunologically competent host that was successfully treated with surgery and combined liposomal amphotericin B and rHuGM-CSF. We discuss the emerging incidence of invasive zygomycosis in immunocompetent patients and the potential clinical application of immunotherapy as adjunctive therapy for invasive mucormycosis in association with liposomal amphotericin B and surgical debridement.     

Longterm survival in acute rhinocerebral mucormycosis with giant cell arteritis and foreign body granulomas

A case of rhinocerebral mucormycosis occurring in a 41-year-old man with insulin-treated diabetes mellitus is reported. Microscopically, biopsy samples obtained from the left ethmoid and middle turbinate sinuses contained fungi that formed mycotic granulomas associated with multinucleate giant cell arteritis. The multinucleate giant cells contained broad, infrequently septate hyphase consistent with mucormycosis. The patient received surgical debridement with extenteration of the left orbit, and intravenous liposome-encapsulated amphotericin B. After 12 months, examination of the patient revealed complete healing. Multinucleate giant cell granulomas and arteritis are only exceptionally associated with rhinocerebral mucormycosis, but these histologic findings may be correlated with a progressive disease with better prognosis.     

Cutaneous mucormycosis and diabetes: about one observation

Mucormycosis is a rare opportunistic infection but a fulminant disease. Varying clinical forms have been described, including cutaneous localisations which are mainly observed in diabetic and burned patients. The cutaneous lesions induced by the mucormycosis affection are often atypical and gangrenous. We report a case of cutaneous mucormycosis in a Tunisian patient with diabetic ketoacidosis. He developed cutaneous necrotic lesions at the low limb. The diagnosis of mucormycosis was not initially evoked but tardily confirmed by identifying mucorale hyphae in tissue sections and Rhizopus oryzae in the sample culture. The treatment consisted of an extensive surgical debridement associated with intravenous perfusion of amphotericin B. The patient had a fatal outcome.     

Rhinocerebral mucormycosis: apropos of 4 new Tunisian cases]

Mucormycosis is a rare opportunistic infection but a fulminant disease. We report the 4 first cases of rhinocerebral mucormycosis diagnosed in Sfax region (Tunisia). They occurred in insulin dependent diabetes and developed varying clinical manifestations from facial cellulites to ocular and cerebral extension. The diagnosis of mucormycosis was not initially evoked, but confirmed tardively by anatomopathologic and mycologic examinations. The evolution was favourable in 2 cases by administration of amphotericine B associated with extensive surgical debridement and correction of the diabetes. Two patients had a fatal outcome. This infection has a severe prognosis and necessitates early diagnosis.     

Fine-needle aspiration cytology of desmoplastic malignant melanoma metastatic to the parotid gland: case report and review of the literature

Rhinocerebral mucormycosis is a rapidly progressing, often fatal fungal infection that occurs commonly in diabetics and immunocompromised individuals. We present 2 cases of rhinocerebral mucormycosis with a paranasal mass. One patient had an intracranial extension. Nasal scrapings and fine-needle aspiration cytology (FNAC) of the paranasal masses showed fungal hyphae morphologically resembling Mucor. Surgical material showed features of mucormycosis. FNAC and scrape smears can give a conclusive diagnosis of mucormycosis, and the patient can be treated with appropriate antifungal therapy and surgical debridement. Preoperative cytology is an effective technique to establish a diagnosis of mucormycosis and obviates the need for a preoperative biopsy.     

Identification of the asexual state of Rhizopus species on histologic tissue sections in a patient with rhinocerebral mucormycosis

Mucormycosis is an infection caused by a group of fungi in the order Mucorales in the phylum Zygomycota. The most well-known form of this disease is rhinocerebral mucormycosis, which usually develops in diabetic or immunocompromised patients. The fungal hyphal elements are easily detected in biopsy specimens by direct or histologic examination. However, the confirmatory identification of the genus or species requires culture of the specimen. This article presents a case of rhinocerebral mucormycosis in which presumptive identification of the genus was made without microbiologic cultures and was based on the extraordinarily rare appearance of fungal sporangia and sporangiospores in histologic tissue sections. Identification of these structures allowed an early and accurate diagnosis of rhinocerebral invasive mucormycosis.     

Treatment of 21 Cases of Invasive Mucormycosis with Amphotericin B Colloidal Dispersion

 The aim of this study was to review the characteristics and outcome of 21 patients with invasive mucormycosis treated with amphotericin B colloidal dispersion (ABCD) in five phase I and phase II studies. Mucormycosis is an increasing concern in immunocompromised patients, in whom mortality exceeds 60%. The standard treatment has been amphotericin B combined with surgical debridement. Twenty-one patients with invasive mucormycosis treated with ABCD, a lipid complex of amphotericin B and cholesteryl sulfate, were identified. Patients were given ABCD on the basis of pre-existing renal insufficiency, development of nephrotoxicity during amphotericin B therapy, or fungal infection that failed to respond to amphotericin B. Response could be evaluated in 20 patients, all of whom had bone marrow or organ transplantation, haematologic malignancies, or diabetes. Infection was disseminated in six patients and localised to the sinuses, lower respiratory tract, or skin in the other patients. ABCD was given at a mean dose of 4.8 mg/kg per infusion for a mean duration of 37 days. Twelve of 20 patients responded to ABCD therapy. Response rates were similar when patients were treated with ABCD alone (4/7) and ABCD combined with surgery (8/13), with more complete response obtained in the latter group. No difference in response rate was observed in leukaemic patients (3/5) or transplant recipients (6/10) compared to diabetics (3/5). No renal or hepatic toxicity was observed. These results compare favourably with the results of standard treatment and suggest that ABCD combined with surgery may be a useful therapy in patients with mucormycosis.     

Rhino-orbitocerebral mucormycosis caused by Apophysomyces elegans

Rhino-orbitocerebral mucormycosis (ROCM) caused by more common zygomycetes (e.g., Mucor) is known to cause rapidly fatal infections in immunocompromised patients. Apophysomyces elegans is an emerging zygomycete that has been reported to cause invasive cutaneous and rhino-orbitocerebral infections in immunocompetent individuals. Limited data exist describing the syndrome of ROCM caused by A. elegans. We describe a recent case and performed a comprehensive literature review to delineate the clinical characteristics of ROCM caused by A. elegans. Our case is a 50-year-old man with diabetes mellitus who presented with facial pain and right eye proptosis. Endoscopic sinus sampling revealed A. elegans. He was treated with liposomal amphotericin B and multiple debridements, with no disease on 1.5-year follow-up examination. Seven cases were identified on literature review, including the present case. Most patients (86%) were male, with a mean age of 40 years. Most patients (71%) did not have predisposing medical conditions. Three patients had predisposing head trauma. All presented with facial and/or periorbital pain. All had magnetic resonance imaging or computed tomography of the head showing intraorbital and/or sinus inflammation. Diagnosis was confirmed by histopathology and deep tissue culture in all cases. All patients required eye exenteration and extensive surgical debridement, in addition to intravenous amphotericin B. Six of the seven patients (86%) recovered. ROCM caused by A. elegans is rarely reported in the literature. Most such infections occurred in immunocompetent patients, often after facial trauma. Survival in ROCM caused by A. elegans is favorable in reported cases, with prompt surgical debridement and antifungal therapy.     

Post-Traumatic Course Complicated by Cutaneous Infection with Absidia corymbifera

 Cutaneous mucormycosis is a rare but serious infection in trauma patients. Reported here is the case of a young patient with cutaneous mucormycosis due to Absidia corymbifera probably caused by a soil-contaminated wound. Despite daily surgical debridement and amphotericin B therapy, cure could be achieved only by amputation of the lower limb.     

Hepatic and small bowel mucormycosis after chemotherapy in a patient with acute lymphocytic leukemia

Mucormycosis is a rare but invasive opportunistic fungal infection with increased frequency during chemotherapy-induced neutropenia. The clinical infections due to Mucor include rhinocerebral, pulmonary, cutaneous, gastrointestinal and disseminated diseases. The first two are the most common diseases and all entities are associated with a high mortality rate. Still hepatic involvement of Mucor is rarely reported. We experienced a case of hepatic and small bowel mucormycosis in a 56-year-old woman after induction chemotherapy for B-cell acute lymphocytic leukemia. Initial symptoms were a high fever unresponsive to broad spectrum antibiotics and pain in the left lower abdominal quadrant. It was followed by septic shock, deterioration of icterus and progressively elevated transaminase. An abdominal CT demonstrated multiple hypodense lesions with distinct margins in both lobes of liver and pericolic infiltration at small bowel and ascending colon. Diagnosis was confirmed by biopsy of the liver. The histopathology of the liver showed hyphae with the right-angle branching, typical of mucormycosis. The patient was managed with amphotericin B and operative correction of the perforated part of the small bowel was performed. However, the patient expired due to progressive hepatic failure despite corrective surgery and long-term amphotericin B therapy.     

Soft tissue infection with Absidia corymbifera in a patient with idiopathic aplastic anemia

We describe a case of primary cutaneous mucormycosis (zygomycosis) in a patient with idiopathic aplastic anemia which responded to surgical debridement and therapy with liposomal amphotericin B. The tissue removed at surgery showed dense infiltration with fungal hyphae on histopathological examination. Primary cultures of tissue on solid media were negative, but Absidia corymbifera was isolated from unprocessed tissue placed in brain heart infusion broth.     

Two Cases of Disseminated Mucormycosis in Patients with Hematological Malignancies and Literature Review

 Two cases of disseminated mucormycosis in patients with underlying hematological disease are described. Both patients presented with fever and pulmonary infiltrates which did not respond to empirical treatment with broad-spectrum antibiotics and antifungal agents, and in both patients there was rapid progression with a fatal outcome. All cultures were negative and the diagnosis was made postmortem. A review of the literature revealed only three recent reports of successful treatment of disseminated mucormycosis. Survival correlated with control of the underlying disease and early diagnosis based on histological examination of biopsy specimens from suspected lesions. Therapy consisted of surgical debridement and amphotericin B. Standard therapeutic schedules need to be defined for this infection.     

A rare case of mucormycosis of median sternotomy wound caused by Rhizopus arrhizus

We describe a case of mucormycosis of median sternotomy wound caused by Rhizopus arrhizus . The patient, a known diabetic and a case of coronary artery disease underwent coronary artery bypass surgery. In the postoperative period, patient developed infection of the median sternotomy wound, from which R. arrhizus was isolated on culture. Patient succumbed in spite of being treated with surgical debridement and amphotericin B. To the best of our knowledge, this is the first reported case of mucormycosis of median sternotomy wound from India.     

Isolated cerebral mucormycosis associated with intravenous drug use

We present an uncommon case of isolated basal ganglia mucormycosis in a patient without any known cause of immunosuppression, but with a history of drug injection. The patient presented a good clinical and radiological response to antifungal treatment without aggressive surgical debridement (liposomal amphotericin B combined with isavuconazole for 4 weeks followed by isavuconazole as maintenance therapy for 10 months).     

Disseminated mucormycosis in healthy adults

Three patients of disseminated mucormycosis are described. None had predisposing factors. Two of them presented with nonspecific symptoms along with acute renal failure and peritonitis. Third patient had fulminating primary cutaneous mucormycosis which disseminated later. Development of acute renal failure with smooth enlargement of both kidneys in an apparently healthy individual or appearance of mould in a wound should raise the suspicion of mucormycosis. The hallmark of the infection was vascular invasion and thrombosis. Antemortem diagnosis could be made in one patient only. All patients had progressive downhill course despite supportive treatment, antibiotic and amphotericin in-B in one patient.     

Non-sinonasal isolated facio-orbital mucormycosis – A case report

Mucormycosis is a rare clinical entity, often affect immunocompromised patients. It is an emergency situation and has poor prognosis. Prompt diagnosis with tissue biopsy, local control of the disease by aggressive surgical debridement and appropriate systemic antifungal treatment improve the prognosis and survival of the patients. Treatment of mucormycosis needs antifungal agents such as Amphotericin B and wide surgical debridement. Early diagnosis and treatment is often needed for survival of the patients. We describe a rare case of mucormycosis affecting facio-orbital area without involving sinon-nasal cavity.     

Apophysomyces elegans causing acute otogenic cervicofacial zygomycosis involving salivary glands.

Zygomycosis is an invasive, life threatening fungal infection that usually affects immunocompromised hosts. In the head and neck region, rhino-orbito-cerebral zygomycosis is more common than the cervicofacial variety. We report the first case of otogenic cervicofacial zygomycosis caused by Apophysomyces elegans involving the salivary glands, an uncommon site of infection. The case began after a trivial trauma in a diabetic patient and despite surgical debridement and liposomal amphotericin B therapy, the patient died due to extensive involvement and metabolic/hemodynamic complications.     

COVID-19 associated mucormycosis – An emerging threat

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) rapidly become a global threaten since its emergence in the end of 2019. Moreover, SARS-CoV-2 infection could also present with co-infection or secondary infection by other virus, bacteria, or fungi. Among them, mucormycosis is a rare but aggressive fungal disease and it mainly affects patients particularly with poorly controlled diabetes mellitus with diabetic ketoacidosis (DKA). We here did a comprehensive review of literature reporting COVID-19 associated with mucormycosis (CAM) cases, which have been reported worldwide. The prevalence is higher in India, Iran, and Egypt than other countries, particularly highest in the states of Gujarat and Maharashtra in India. Poor diabetic control and the administration of systemic corticosteroids are the common precipitating factors causing mucormycosis in the severe and critical COVID-19 patients. In addition, COVID-19 itself may affect the immune system resulting in vulnerability of the patients to mucormycosis. Appropriate treatments of CAM include strict glycemic control, extensive surgical debridement, and antifungal therapy with amphotericin B formulations.     

Disseminated zygomycosis with involvement of the central nervous system

Zygomycosis of the central nervous system (CNS) can manifest in three distinct clinical forms, as rhinocerebral zygomycosis, as disseminated zygomycosis with CNS involvement, and as isolated cerebral zygomycosis. We present a case of a 2-year-old boy with leukaemia and disseminated zygomycosis, caused by Absidia corymbifera , involving the brain, spinal cord, lung and liver. The child received treatment with liposomal amphotericin B and posaconazole for 6 months. Although the lesions of the lungs and liver resolved, those of the CNS persisted and the child is in a vegetative state. A review of the literature after 2004 identified ten additional cases of disseminated zygomycosis with cerebral involvement, all but one of which had concurrent lung infection. The most common underlying disease in these cases was haematological malignancy and the mortality rate was 70%. Disseminated zygomycosis with cerebral involvement is a fatal disease. Early recognition and prompt intervention with combined medical and surgical treatment may improve the outcome.