rifampin and Aspergillosis

Optimization of antifungal therapy with voriconazole can be challenging due to inter- and intrapatient variability in voriconazole pharmacokinetics (PK). In this case, we introduce challenges in voriconazole therapy due to drug-drug interactions, autoinduction, and saturable metabolism.. A 32-year-old male on chronic prednisone developed central nervous system (CNS) aspergillosis. He was started on high-dose intravenous (IV) voriconazole 8.5 mg/kg every 12 hours due to concerns for lasting induction effects of recent rifampin therapy. The initial voriconazole trough was 2 μg/mL. Frequent dose adjustments were made to maintain the therapeutic trough goal. On day 24 of voriconazole therapy, his trough was undetectable on IV voriconazole 5.5 mg/kg every 12 hours. His dose was escalated to 8.5 mg/kg every 12 hours to avoid subtherapeutic levels and therapeutic failure. On day 48, his trough level was 1.1 μg/mL on the same dose. His regimen was changed to 6.5 mg/kg every 8 hours at this point. Sixteen days after this regimen on day 74 of voriconazole therapy, his trough was 27.2 μg/mL indicating saturable PK of voriconazole in the absence of interacting drugs.. Our findings highlight the unpredictable PK of voriconazole and reinforce the importance of continuous therapeutic drug monitoring in critically ill patients.

Topics: Adult; Antifungal Agents; Aspergillosis; Aspergillus fumigatus; Drug Interactions; Drug Monitoring; Humans; Male; Rifampin; Safety-Based Drug Withdrawals; Voriconazole

Invasive aspergillosis is an opportunist infection in immunosuppressed hosts among the most difficult to diagnose and to treat. A wide variety of clinical forms exist which may not require the same treatment for each of them. Intravenous amphotericin B and itraconazole are the only available antifungal agents. Amphotericin B is often considered as the gold standard treatment despite its high toxicity particularly with high dosage (1-1.5 mg/kg/day) and its poor results namely in bone marrow transplant recipients. Lipidic amphotericin B is less toxic allowing administration of higher dose however relevant data are limited. Itraconazole is an excellent anti Aspergillus antifungal with low toxicity, however there is a wide intersubject variation in intestinal absorption. It may represent a valuable alternative to amphotericin B in case of intolerance or as a relay treatment and possibly in some cases as a first choice treatment. More studies are necessary particularly in granulopenic patients. Comparative study are urgently needed between both drugs and with new molecules to indicate the best treatment according to the clinical form. The use of hematopoietic growth factors and surgery may improve the outcome.

Topics: Amphotericin B; Antifungal Agents; Aspergillosis; Drug Therapy, Combination; Flucytosine; Humans; Itraconazole; Lung Diseases, Fungal; Rifampin

Invasive aspergillosis is generally a life-threatening invasive opportunistic mycosis affecting principally the upper and lower respiratory tract. Therapeutic response rates vary considerably from one host group to another with particularly high mortality rates in bone marrow transplant, liver transplant and patients with aplastic anaemia or AIDS. Only two drugs are useful for therapy, amphotericin and itraconazole. Recent advances in the formulation of amphoterin B (AmBisome and Amphocil) have resulted in intravenous preparations with lower toxicity, particularly nephrotoxicity, but it has yet to be shown that they have an increased therapeutic index for the treatment of invasive aspergillosis. Itraconazole can only be used orally and in some particularly high-risk or critically ill patients adequate serum concentrations cannot be achieved. The addition of flucytosine or rifampicin to amphotericin B therapy has, at best, only a marginal benefit. Surgery is essential for some manifestations of invasive aspergillosis. This article reviews therapeutic strategies including criteria for initiation of therapy, combination and sequential therapy, duration of therapy and secondary prophylaxis and indications for surgery in invasive aspergillosis.

Topics: AIDS-Related Opportunistic Infections; Amphotericin B; Aspergillosis; Cholesterol Esters; Drug Carriers; Drug Therapy, Combination; Flucytosine; Humans; Immunocompromised Host; Infusions, Intravenous; Itraconazole; Liposomes; Opportunistic Infections; Rifampin

Topics: Amphotericin B; Aspergillosis; Candidiasis; Cryptococcosis; Drug Synergism; Drug Therapy, Combination; Flucytosine; Humans; Mycoses; Prospective Studies; Rifampin

We report the first know case of disseminated fungal infection due to Fusarium proliferatum in a bone marrow transplant recipient to our knowledge. Fusarium was cultured from the blood, a paranasal sinus, and necrotic skin lesions. The isolate was sensitive to amphotericin B and on further sensitivity testing, synergy was demonstrated using rifampin in combination with amphotericin B. The patient had this infection while she was receiving alternate-day amphotericin, rifampin, and 5-flucytosine (5-FC) therapy. The infection was documented within 48 h of discontinuing daily granulocyte transfusions, which she had received for 3 weeks. The 5-FC was discontinued when sensitivities showed the organism resistant. After 6 weeks of treatment she showed complete remission of the infection, although neutrophil counts remained below 0.25 X 10(9)/L. From this case and from a review of the literature, it appears that synergic antifungal agents combined with leukocyte transfusions may be beneficial in the successful treatment of fusariosis in the compromised host.

Topics: Amphotericin B; Antineoplastic Combined Chemotherapy Protocols; Aspergillosis; Bone Marrow Transplantation; Child, Preschool; Combined Modality Therapy; Female; Fusarium; Humans; Mycoses; Neutropenia; Opportunistic Infections; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Rifampin; Skin; Spider Bites; Staphylococcal Infections

Topics: Adult; Antifungal Agents; Aspergillosis; Azoles; Candidiasis; Cyclosporine; Drug Interactions; Erythromycin; Female; Humans; Kidney Transplantation; Legionnaires' Disease; Male; Middle Aged; Opportunistic Infections; Postoperative Complications; Rifampin; Streptococcal Infections; Tuberculosis, Pulmonary

Topics: Amphotericin B; Aspergillosis; Candidiasis; Cryptococcosis; Drug Synergism; Drug Therapy, Combination; Flucytosine; Humans; Mycoses; Prospective Studies; Rifampin

Topics: Adult; Amphotericin B; Antifungal Agents; Aspergillosis; Bone Marrow Transplantation; Brain Diseases; Female; Humans; Rifampin; Transplantation, Homologous

Topics: Amphotericin B; Aspergillosis; Child; Femur; Flucytosine; Humans; Male; Osteomyelitis; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Rifampin

Topics: Abscess; Adrenal Gland Diseases; Amphotericin B; Aspergillosis; Aspergillus fumigatus; Diagnosis, Differential; Drainage; Drug Therapy, Combination; Humans; Ketoconazole; Male; Middle Aged; Opportunistic Infections; Rifampin; Sarcoidosis

Topics: Acute Disease; Adult; Aspergillosis; Aspergillus fumigatus; Cyclosporins; Dose-Response Relationship, Drug; Female; Graft Rejection; Heart Transplantation; Humans; Lung Diseases, Fungal; Rifampin

Topics: Adolescent; Amphotericin B; Aspergillosis; Drug Therapy, Combination; Granulomatous Disease, Chronic; Humans; Male; Rifampin

Topics: Amphotericin B; Aspergillosis; Child, Preschool; Drug Therapy, Combination; Granulomatous Disease, Chronic; Humans; Male; Osteomyelitis; Rifampin

We have reported the successful treatment of a patient with acute leukemia complicated by pulmonary aspergillosis, a commonly fatal situation. Specific diagnosis was obtained easily by transbronchial lung biopsy. Our therapeutic approach included aggressive treatment of both the underlying malignant process and the aspergillosis with a combination of amphotericin B and rifampin.

Topics: Amphotericin B; Aspergillosis; Drug Therapy, Combination; Humans; Leukemia, Myeloid; Lung Diseases, Fungal; Male; Middle Aged; Rifampin

Suboptimal doses of amphotericin B in combination with either rifampin or 5-fluorocytosine were better than single-drug therapy in the treatment of disseminated Aspergillus fumigatus infection in mice. Despite the increased effectiveness of combination therapy, none of the therapeutic regimens we used completely eradicated infections in the mice when evaluated by mycological culture, even in long-term survivors.

Topics: Amphotericin B; Animals; Aspergillosis; Aspergillus fumigatus; Cytosine; Drug Therapy, Combination; Female; Flucytosine; Mice; Mice, Inbred AKR; Rifampin

Pulmonary aspergillosis developed in a 62-year-old man with acute myelogenous leukemia. Therapy with amphotericin B and 5-fluorocytosine was begun. Synergy between amphotericin B and rifampin was demonstrated in vitro, and therapy with firampin replaced 5-fluorocytosine. Progressive clearing of the pulmonary lesion ensued, suggesting in vivo efficacy as well. Further studies of patients utilizing this regimen are warranted.

Topics: Amphotericin B; Aspergillosis; Aspergillus fumigatus; Drug Synergism; Flucytosine; Humans; In Vitro Techniques; Leukemia, Myeloid, Acute; Lung Diseases, Fungal; Male; Middle Aged; Radiography; Rifampin

The recent increased use of steriods, immunosuppressive agents and cytotoxic drugs has been associated with a rise in the incidence of significant fungal disease. The first case of bilateral renal aspergillosis without disseminated involvement is reported. A multitherapeutic approach, including surgical evacuation of masses of hyphae, parenteral antimycotic chemotherapy and topical instillations of amphotericin B, were necessary to clear the kidneys. Newer systemic agents such as 5-fluorocytosine and rifampicin were also used. Treatment of fungal infections of the urinary tract is discussed.

Topics: Adult; Amphotericin B; Aspergillosis; Drug Synergism; Flucytosine; Humans; Kidney Diseases; Male; Rifampin; Therapeutic Irrigation

Topics: Adult; Aspergillosis; Hemoptysis; Humans; Isoniazid; Lung; Lung Diseases, Fungal; Male; Radiography; Rifampin; Tuberculosis, Pulmonary

Topics: Administration, Oral; Adult; Antifungal Agents; Antitubercular Agents; Aspergillosis; Benzene Derivatives; Bronchial Fistula; Chronic Disease; Female; Humans; Imidazoles; Lung Diseases, Fungal; Pneumothorax; Radiography; Rifampin; Tuberculosis, Pulmonary