Amphotericin B colloidal dispersion: an effective drug for the treatment of mucormycosis in China.

Objective: Mucormycosis has emerged as an increasingly important cause of morbidity and mortality in immunocompromised patients, but the effective drugs for the treatment are limited. Hence, the study aimed to summarize the characteristics of mucormycosis in patients with hematological malignancies, and investigate the efficacy and safety of Amphotericin B Colloidal Dispersion (ABCD) in treating mucormycosis. Methods: In this study, patients with mucormycosis complicated by hematological malignancies who received ABCD at the First Affiliated Hospital of Zhengzhou University from April 2021 to May 2022 were retrospectively enrolled. The clinical data of the enrolled patients were collected, and then, the drug response at 2 weeks, 4 weeks, and the end of treatment; the survival rate at 4, 8, and 12 weeks; and the laboratory-related indicators and adverse events (AEs) associated with ABCD were evaluated. Results: In total, 9 patients with mucormycosis complicated by hematological malignancies were enrolled. The main symptoms were fever, cough, and chest pain. In addition, reversed halo signs (RHS) were found on chest CTs. The responses to ABCD at 2 weeks, 4 weeks, and the end of treatment were 100% (9/9), 77.8% (7/9), and 77.8% (7/9), respectively. The survival rates of the patients at 4, 8, and 12 weeks were 77.8% (7/9), 66.7% (6/9), and 66.7% (6/9), respectively. Among laboratory-related indicators, white blood cell (WBC) counts were significantly increased from baseline after 1 and 2 weeks of ABCD treatment (P<0.05), whereas neutrophil counts were only increased significantly from baseline at 2 weeks post-treatment (P<0.05). The most common AEs were infusion-related AEs manifesting as fever, chills, and pruritus. Moreover, none of the patients suffered from renal injury once again. Conclusion: ABCD is a promising treatment strategy for patients with mucormycosis complicated by hematologic malignancies, showing remarkable efficacy and safety.

COVID-19 associated mucormycosis: A Descriptive Multisite Study from India.

BACKGROUND AND AIMS: Mucormycosis is an invasive fungal infection and carries a significant morbidity and mortality. A number of cases of mucormycosis have been reported in association with COVID-19. In this study, a consortium of clinicians from various parts of India studied clinical profile of COVID-19 associated mucormycosis (CAM) and this analysis is presented here. METHODS: Investigators from multiple sites in India were involved in this study. Clinical details included the treatment and severity of COVID-19, associated morbidities, as well as the diagnosis, treatment and prognosis of mucormycosis. These data were collected using google spreadsheet at one centre. Descriptive analysis was done. RESULTS: There were 115 patients with CAM. Importantly, all patients had received corticosteroids. Diabetes was present in 85.2% of patients and 13.9% of patients had newly detected diabetes. The most common site of involvement was rhino-orbital. Mortality occurred in 25 (21.7%) patients. On logistic regression analysis, CT scan-based score for severity of lung involvement was associated with mortality. CONCLUSION: Universal administration of corticosteroids in our patients is notable. A large majority of patients had diabetes, while mortality was seen in ∼1/5th of patients, lower as compared to recently published data.

Concomitant cerebral aspergillosis and mucormycosis in an immunocompetent woman treated with corticosteroids.

We present the case of an immunocompetent 55-year-old woman, treated with corticosteroids, developing a cerebral fungal infection with autoptic ascertainment of aspergillosis and mucormycosis. This is the first report of cerebral co-infection by mucorales and aspergillus in an immunocompetent host. A possible explanation is that corticosteroids, even if taken for a short time, led to a transient lowering of immune function and contributed to negative outcome.

Gastric mucormycosis complicated by a gastropleural fistula: A case report and review of the literature.

RATIONALE: Mucormycosis is a rare opportunistic fungal infection with poor prognosis. The incidence of mucormycosis has been increasing, and it is a threat to immunocompromised hosts. We present a case of gastric mucormycosis complicated by a gastropleural fistula during immunosuppressive treatment for adult-onset Still disease (AOSD). PATIENT CONCERNS: An 82-year-old woman diagnosed with AOSD who developed gastric ulcers during the administration of an immunosuppressive therapy with corticosteroids, cyclosporine, and tocilizumab complained of melena and epigastralgia. Esophagogastroduodenoscopy showed multiple ulcers covered with grayish or greenish exudates. DIAGNOSES: The patient diagnosed with mucormycosis based on culture and biopsy of the ulcers, which showed nonseptate hyphae branching at wide angles. Mucor indicus was identified using polymerase chain reaction. INTERVENTIONS AND OUTCOMES: Although liposomal amphotericin B was administered, gastric mucormycosis was found to be complicated by a gastropleural fistula. The patient died because of pneumonia due to cytomegalovirus infection, and autopsy revealed the presence of Mucorales around the fistula connecting the stomach and diaphragm. LESSONS: Gastric mucormycosis is refractory to treatment and fatal. Surgical resection, if possible, along with antifungal drugs can result in better outcomes.

Mucormycosis diagnosed during induction chemotherapy in five pediatric patients with acute lymphoblastic leukemia.

Mucormycosis in pediatric oncology patients is a rare invasive fungal infection associated with significant morbidity and mortality. We describe five patients diagnosed with mucormycosis during induction chemotherapy for acute lymphoblastic leukemia at our institution. All of the patients in our series survived, some in spite of having disseminated disease. Most of the patients' chemotherapy was modified with the aim of controlling their leukemia while minimizing immunosuppression until their fungal infection was under control. Although mucormycosis is frequently fatal, rapid diagnosis and a multidisciplinary approach can lead to excellent outcomes, even in patients undergoing intensive chemotherapy.

Voriconazole associated mucormycosis in a patient with relapsed acute lymphoblastic leukemia and hematopoietic stem cell transplant failure: A case report.

The patients with hematologic malignancies and hematopoietic stem cell transplantation (HSCT) recipients are at high risk for invasive fungal diseases (IFDs) mainly due to the severe and prolonged neutropenia related to high-dose chemotherapy. Voriconazole prophylaxis is recommended for possible IFDs. Mucormycosis is a fulminant infection, which may occur after voriconazole prophylaxis for invasive aspergillosis in immunocompromised hosts. Here, we report mucormycosis after 4 months of voriconazole prophylaxis in a young patient with relapsed acute lymphoblastic leukemia and hematopoietic stem cell transplant failure and discuss the clinical manifestation, imaging, laboratory findings and therapeutic regimens. Clinician's awareness of this entity and timely diagnosis using conventional and molecular methods are the promising approach for the management of this devastating infection.

Disseminated mucormycosis infection after the first course of dose-modified R-EPOCH for advanced-stage lymphoma.

We report the case of a 63-year-old man who presented at our hospital after experiencing fever and dyspnea for more than 1 month. Because his general condition was deteriorating, he was referred to our intensive care unit. He needed critical care and was treated with vasopressors, artificial ventilation, and continuous hemodialysis. Considering his systemic condition, hematological malignancy was suspected. Bone marrow and skin biopsies were performed, and the condition was diagnosed as diffuse large B-cell lymphoma. On the 15th day, suspecting infectious lung disease, we performed bronchoscopy, which showed Rhizopus infection. Thus, the patient was administered high-dose liposomal amphotericin B (10 mg/kg) therapy. On the 54th day, he died of a massive pulmonary hemorrhage. Autopsy revealed mucormycosis infection in multiple organs, including the lungs and liver. Vigilance regarding possible mucormycosis infection is required, even after initial chemotherapy in patients whose bone marrow is significantly affected by lymphoma cells and leukemic changes.

Activity and safety of combination chemotherapy with methotrexate, ifosfamide, l-asparaginase and dexamethasone (MILD) for refractory lymphoid malignancies: a pilot study.

Optimal salvage chemotherapy has not been established for lymphoid malignancy, which is refractory to the conventional cyclophosphamide, doxorubicin, vincristine, and prednisone regimen. To explore an effective regimen, we conducted a phase I pilot study of combination chemotherapy with methotrexate, ifosfamide, l-asparaginase and dexamethasone (MILD), which are unaffected by MDR1-encoded P-glycoprotein. A total of 18 patients with lethal lymphoid malignancy were enrolled over a 2-yr period. The median age was 63 yr. Eleven patients had T/NK-cell malignancies, six had B-cell malignancies, and one was diagnosed with a blastic plasmacytoid dendritic cell neoplasm. Patients aged >/=60 and <60 yr were planned to receive a set of starting doses of methotrexate and ifosfamide, which should induce myelosuppression. Eleven patients completed two courses of MILD therapy. Treatment-related death because of systemic mucormycosis was observed in one patient. Major treatment-related adverse events were grade 3 or more hematologic toxicities, which included lymphopenia corresponding to dose-limiting toxicity. The most common grade 3 non-hematologic toxicity was febrile neutropenia. Of the 14 evaluated patients, three achieved a complete response, and four showed a partial response. The overall response rate was 57%. It was very interesting that all of seven responders had T/NK-cell malignancies. MILD therapy was feasible and presented acceptable toxicity in patients with refractory or lethal lymphoid malignancies. The efficacy for T/NK-cell malignancies should be further evaluated.

[Case report of mucormycosis in a patient with secondary methimazole-induced agranulocytosis]. / Mucormicosis en un paciente con agranulocitosis secundaria a metimazol. Informe de un caso.

Agranulocytosis is a rare side effect of antithyroid drugs, it occurs in less than 0.5% of patients, usually during the first few months of treatment. It is considered to be the most serious adverse effect of these medications since it may be complicated by serious, life-threatening infections. Mucormycosis is a severe mycotic infection that usually develops in immunocompromised hosts, such aspatients with diabetes mellitus, hematologic malignancies or immunosuppressive therapy. The association of mucormycosis with methimazole-induced agranulocytosis has not been previously described. The objective of this case presentation is to analyze the case ofa woman with diffuse toxic goiter and methimazole-induced agranulocytosis who developed rhino-palatal mucormycosis.

Mucormicosis en un paciente con agranulocitosis secundaria a metimazol: informe de un caso / Case report of mucormycosis in a patient with secondary methimazole-induced agranulocytosis

La agranulocitosis es una complicación poco frecuente de los medicamentos antitiroideos, se presenta en menos de 0.5% de los pacientes en los primeros meses de tratamiento. Se considera el efecto adverso más grave de estos medicamentos, ya que se puede complicar con infecciones severas con una tasa alta de mortalidad. La mucormicosis es una infección micótica severa observada en huéspedes inmunocomprometidos como pacientes con diabetes, neoplasias hematológicas o con tratamiento inmunosupresor; sin embargo, la asociación de mucormicosis con agranulocitosis por metimazol no se ha reseñado previamente. El objetivo de este informe es analizar el caso de una mujer con bocio tóxico difuso y agranulocitosis asociada a metimazol, quien desarrolló mucormicosis rinopalatina.

Agranulocytosis is a rare side effect of antithyroid drugs, it occurs in less than 0.5% of patients, usually during the first few months of treatment. It is considered to be the most serious adverse effect of these medications since it may be complicated by serious, life-threatening infections. Mucormycosis is a severe mycotic infection that usually develops in immunocompromised hosts, such aspatients with diabetes mellitus, hematologic malignancies or immunosuppressive therapy. The association of mucormycosis with methimazole-induced agranulocytosis has not been previously described. The objective of this case presentation is to analyze the case ofa woman with diffuse toxic goiter and methimazole-induced agranulocytosis who developed rhino-palatal mucormycosis.

'Primary cutaneous mucormycosis during induction chemotherapy in a child with acute lymphoblastic leukemia'.

We report a child with acute lymphoblastic leukemia who developed primary cutaneous mucormycosis at the site of lumbar puncture during induction chemotherapy. Though high mortality rates are reported with invasive mucormycosis, prompt biopsy, early identification and antifungal therapy using a combination regime of amphotericin-B and rifampicin along with extensive surgical debridement led to complete cure of the lesions in the index case.

Prior invasive pulmonary and cerebellar mucormycosis is not a primary contraindication to perform an autologous stem cell transplatation in leukemia.

Mucormycosis infections, caused by fungi of the families Rhizopus, Mucor or Absidia, are typically rapidly progressive and often fatal. We report a 27-year-old male with acute myeloid leukemia (AML) developing an invasive pulmonary-CNS mucormycosis during the neutropenic period after salvage induction chemotherapy; the infection was successfully controlled with surgery and antifungal therapy. The patient received two courses of consolidation chemotherapy and underwent autologous stem cells transplantation (ASCT) while receiving secondary antifungal systemic prophylaxis with liposomal Amphotericin B (L-AMB, Ambisome). There was no clinical, radiological or microbiological evidence of mycotic reactivation during the bone marrow transplantation (BMT) procedure.

Pharmacokinetics of aluminoxamine and ferrioxamine and dose finding of desferrioxamine in haemodialysis patients.

We investigated the pharmacokinetics of desferrioxamine and its chelated compounds aluminoxamine and ferrioxamine in normal volunteers and haemodialysis patients with and without iron overload. Desferrioxamine was administered in a single dose of 30 mg per kg body-weight was a 30-min infusion to five healthy volunteers and to 20 haemodialysis patients (five patients without haemosiderosis and 15 patients with haemosiderosis). The interdialytic half-life of ferrioxamine was 2.2 h in normal volunteers, 13.3 h in dialysis patients without haemosiderosis, and 24.6 h in patients with haemosiderosis. There was no interdialytic elimination of aluminoxamine. In a second study, seven dialysis patients received 5, 10, and 20 mg per kg body-weight desferrioxamine in a random order with a time interval of 2 weeks. The peak serum concentrations after these doses were 4.1 +/- 2.9, 6.4 +/- 2.9, and 10.7 +/- 7.1 mumol/l for ferrioxamine and 2.8 +/- 1.5, 3.1 +/- 1.5, and 4.2 +/- 1.7 mumol/l for aluminoxamine. Thus, a 4-fold increase in desferrioxamine dosage resulted in a 2.7-fold increase in peak ferrioxamine levels and in only a 1.5-fold increase in peak aluminoxamine levels. We conclude that dialysis patients, especially those with haemosiderosis, are exposed to persistently elevated ferrioxamine levels. Weekly doses of 5-10 mg/kg of desferrioxamine would be sufficient for aluminium chelation therapy.