Fluconazole therapy for chronic disseminated candidiasis in patients with leukemia and prior amphotericin B therapy

Article Abstract:

Advances have been made in the treatment of leukemia, a type of blood cancer. Some leukemia patients can now achieve complete remission and survive longer. However, infection frequently prevents the development of complete remission. Candidiasis is an infection with the yeast-like fungi Candida, and is a frequent cause of death of leukemia patients. Disseminated, or widespread, candidiasis, can be classified as acute or chronic. Acute disseminated candidiasis is characterized by skin lesions, fungi in the blood, low blood pressure, and develops over a period of days. Chronic disseminated candidiasis develops over months and is associated with progressive deterioration. A chronic form of disseminated candidiasis, referred to as hepatosplenic candidiasis, often occurs in leukemia patients. Hepatosplenic candidiasis develops during neutropenia, a decrease in numbers of neutrophils (a type of white blood cell), which is a common side effect of chemotherapy or bone marrow transplantation. This fungal infection is characterized by fever, enlargement of the liver and spleen, abdominal tenderness, and abscesses in the liver, spleen, and kidney. Intravenous amphotericin B and flucytosine are used to treat hepatosplenic candidiasis, but are effective in only 50 percent of patients. The efficacy of the fluconazole, a drug that has been shown to be effective against various fungal infections, was assessed in 16 leukemia patients with hepatosplenic candidiasis. Fluconazole was effective in 14 patients, including seven patients for whom amphotericin B therapy had failed, and seven patients who developed toxicities related to amphotericin B treatment. Anticancer treatment was continued in 12 patients without recurrence of the fungal infection. Fluconazole caused few side effects and was tolerated by the patients. However, infection with another fungus, Aspergillus, occurred in three patients, and two of these patients did not survive. It is concluded that fluconazole is a safe and effective treatment for hepatosplenic candidiasis. (Consumer Summary produced by Reliance Medical Information, Inc.)

Drug therapy, Leukemia

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Hepatosplenic candidiasis: successful treatment with fluconazole

Article Abstract:

Hepatosplenic candidiasis is the infection of the spleen and liver with the yeast-like fungi Candida, and is characterized by the formation of very small abscesses in the liver, spleen, and kidney. It most often develops in patients with leukemia, a type of blood cancer, who are recovering from neutropenia, a decreased number of neutrophils, a type of white blood cell. Signs and symptoms of hepatosplenic candidiasis include fever, abdominal pain, loss of appetite, nausea, and vomiting. Hepatosplenic candidiasis may be difficult to treat and may persist for months, despite treatment. The effectiveness of the drug fluconazole was assessed in six patients with leukemia and hepatosplenic candidiasis, which did not respond to treatment with the antifungal agents amphotericin B and flucytosine. Fever developed in all patients, who ranged in age from 3 to 44 years. Nausea and vomiting occurred in three patients, and imaging methods revealed abnormalities of the liver (six patients), the spleen (five patients), and the kidney (three patients). Daily doses of 200 to 400 milligrams (mg) of fluconazole for adults for 2 to 14 months improved symptoms. Fever and other symptoms were improved within two to eight weeks, and lesions began to heal within four to eight weeks in all patients. Complete healing of the lesions occurred within four weeks in two patients, four to five months in three patients, and within 13 months in one patient. Leukemia recurred in three patients, including two who died, and bone marrow transplantation was successfully performed in two other patients. These findings show that fluconazole is effective in treating hepatosplenic candidiasis that is not responsive to treatment with amphotericin B and flucytosine. (Consumer Summary produced by Reliance Medical Information, Inc.)

Case studies, Immunosuppression

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Mucormycosis: association with deferoxamine therapy

Article Abstract:

Mucormycosis is a rare, often fatal opportunistic fungal infection that has been documented in patients with poorly controlled diabetes, acute leukemia and immunosuppressive diseases. In the past two years this disease has also been diagnosed in patients being treated with deferoxamine, a medication for chelating iron and/or aluminum overload in patients undergoing kidney dialysis or frequent transfusions. This case study describes a fatal mucormycosis infection in a 56-year-old female with myelodysplastic syndrome (defective formation of the spinal cord) who was treated with deferoxamine for transfusion-related iron overload. The patient initially entered the hospital with fever and nonproductive cough and was treated for presumptive pneumonia. However, over the following week her condition worsened, her chest x-ray showed a 6-cm mass and head CT scan (computed tomography) revealed a 3-cm by 4-cm right brain lesion. Despite treatment with additional antibiotics and mechanical ventilation, the patient's neurological status deteriorated and she died. Post mortem examination revealed mucormycosis fungal infection of the brain and lung, with tissue invasion through blood vessel walls and multiple abscesses. It is suggested that deferoxamine may alter the balance between iron metabolism in the patient and the iron requirements of the fungus. The paradox of an increased risk of mucormycosis while a patient is being treated with a medication that binds iron may be explained by understanding how pathogenic organisms acquire iron from the patient's body. It is not known whether the iron overload, the chelating drug, or both increase the risk for mucormycosis infection.

Research, Analysis, Causes of, Iron in the body, Iron (Nutrient), Medical microbiology, Mucormycosis, Deferoxamine

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