A Pan-American 5-Year Study of Fluconazole Therapy for Deep Mycoses in the Immunocompetent Host

Díaz, Manuel Concha; Negroni, Ricardo; Montero-Gei, F.; Castro, Luiz Guilherme Martins; Sampaio, S. A. P.; Borelli, Dante; Restrepo, Ángela; Franco, Liliana; Bran, Jose L.; Arathoon, Eduardo; Stevens, David A.

doi:10.1093/clinids/14.supplement_1.s68

Cited by 126 publications

(56 citation statements)

References 13 publications

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“…A large therapeutic armamentarium is available for patients with paracoccidioidomycosis. Several classes of antimycotic drugs have been used in the treatment of paracoccidioidomycosis, including sulfonamides (sulfadiazine, sulfadoxine, sulfamethoxypyridazine, cotrimazine, and trimethoprim-sulfamethoxazole), amphotericin B, azoles (ketoconazole, itraconazole, and fluconazole), and terbinafine [6,7,12,13].…”

Section: Discussionmentioning

confidence: 99%

An Open-Label Comparative Pilot Study of Oral Voriconazole and Itraconazole for Long-Term Treatment of Paracoccidioidomycosis

Telles

Goldani

Schlamm

et al. 2007

Clinical Infectious Diseases

100

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Background. In previous studies, itraconazole was revealed to be an effective therapy and was considered to be the gold standard treatment for mild-to-moderate acute and chronic clinical forms of paracoccidioidomycosis. A pilot study was conducted to investigate the efficacy, safety, and tolerability of voriconazole for the long-term treatment of acute or chronic paracoccidioidomycosis, with itraconazole as the control treatment. Methods.A randomized, open-label study was conducted at 3 Brazilian tertiary care hospitals. Patients were randomized (at a 2:1 ratio) to receive oral therapy with voriconazole or itraconazole for 6 months. Patients receiving у1 dose of study drug were evaluated for safety; patients with confirmed paracoccidioidomycosis who completed у6 months of therapy (treatmentevaluable patients) were evaluated for treatment efficacy. Satisfactory global response was assessed at the end of treatment.Results. Fifty-three patients were evaluated for treatment safety (35 received voriconazole, and 18 received itraconazole). Both drugs were well tolerated. The most common treatment-related adverse events in the voriconazole group included abnormal vision, chromatopsia, rash, and headache; the most common treatment-related adverse events in the itraconazole group included bradycardia, diarrhea, and headache. Liver function test values were slightly higher in patients receiving voriconazole than in those receiving itraconazole; 2 patients in the voriconazole group were withdrawn from treatment because of increased liver function test values. In the intent-to-treat populations, the satisfactory response rate (i.e., complete or partial global response) was 88.6% among the voriconazole group and 94.4% among the itraconazole group. The response rate among treatment-evaluable patients was 100% for both treatment groups; no relapses were observed after 8 weeks of follow-up.Conclusions. This is, to our knowledge, the first study to demonstrate that voriconazole is as well tolerated and effective as itraconazole for the long-term treatment of paracoccidioidomycosis.

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Section: Discussionmentioning

confidence: 99%

An Open-Label Comparative Pilot Study of Oral Voriconazole and Itraconazole for Long-Term Treatment of Paracoccidioidomycosis

Telles

Goldani

Schlamm

et al. 2007

Clinical Infectious Diseases

100

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“…Fluconazole has been tried in some paracoccidioidomycosis patients (90); to date, the results indicate that this triazole is also highly active. One of its advantages is its solubility in water, which allows rapid penetration into the fluid compartments of the patient; this drug is also available for parenteral administration.…”

Section: Imidazole Derivativesmentioning

confidence: 99%

Paracoccidioidomycosis: an update

1993

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This review summarizes knowledge on various aspects of paracoccidioidomycosis. Mycelial propagules, chlamydospores, and arthroconidia exhibit thermal dimorphism; arthroconidia are infectious in animals and, by electron microscopy, appear well provided for survival. The mycelial-to-yeast-phase transformation requires a strict control of glucan synthesis probably mediated by membrane enzymes. Hormonal influences on the transformation of the fungus (mycelium or conidium to yeast phase) have been demonstrated. Estrogen-binding proteins have been detected in the fungal cytosol, and during the transformation novel proteins are produced as a result of estradiol incorporation. Clinical forms have been better defined on the basis of better experimental models. Emphasis has been placed on the lungs as the portal of entry and on the existence of silent pulmonary infections. A specific Paracoccidioides brasiliensis antigen, the 43-kDa glycoprotein (Gp43), has been identified, characterized, and cloned. This has led to improved reproducibility and specificity of serologic tests. The depression of cell-mediated immune responses has been associated with severe disease in humans and in the experimental host. T-cell subsets in patients' tissues were characterized by means of monoclonal antibodies, and a reduced CD4/CD8 ratio was demonstrated. This has been related to alterations in lymphokine and tumor necrosis factor production, production of antigen-antibody complexes, etc. Amphotericin B has provided effective therapy. Azole derivatives have also improved prognosis and facilitated therapy. Itraconazole is presently the drug of choice, yet incapacitating sequelae (mainly pulmonary fibrosis) still constitute major problems.

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“…This is an interesting topic for further study. FLC is considered the second-line treatment for sporotrichosis (4). In spite of the poor activity that this drug has shown in this and other studies (6,17), its clinical efficacy has been estimated to be 71% for cases of lymphocutaneous infection (10).…”

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confidence: 95%

In Vitro Antifungal Susceptibilities ofSporothrix schenckiiin Two Growth Phases

Trilles

Fernández-Torres

Lazéra

et al. 2005

Antimicrob Agents Chemother

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We have determined the antifungal susceptibilities of 34 clinical isolates of the dimorphic fungus Sporothrix schenckii to 11 drugs using a microdilution method. In general, the type of growth phase (mycelial or yeast) and the temperature of incubation (30 or 35°C) exerted a significant influence on the MICs.Sporothrix schenckii is a thermally dimorphic fungus and the most common agent of subcutaneous mycosis in Latin America (2, 12). Pulmonary and disseminated sporotrichosis can also occur when S. schenckii conidia are inhaled (16). Itraconazole (ITC) is generally used for the treatment of lymphocutaneous infection (3, 13, 21), while amphotericin B (AMB) is indicated for severe infections or when ITC therapy fails (9). Although these drugs are generally effective, the long duration of therapy and the strong toxicity of AMB make it necessary to explore new alternatives for the treatment of severe infections.The infective form of sporotrichosis is the yeast phase (Y). However, the reference methods for in vitro antifungal susceptibility testing propose conditions only for the testing of its mycelial phase (M) (19). Testing of Y requires the use of other conditions. Although the optimal temperature for the in vitro growth of S. schenckii ranges from 25°C to 30°C (7), the reference method recommends a temperature of incubation of 35°C. The few studies that have determined the in vitro antifungal susceptibility of S. schenckii have used as the inoculum a mixture of hyphae and conidia obtained from its M (8, 14). We have evaluated the in vitro activities of 11 antifungal agents against clinical isolates of S. schenckii in order to determine if the form of growth and temperature of incubation can influence the MICs.A total of 34 isolates were tested (18 were from patients with disseminated sporotrichosis, 15 were from patients with the lymphocutaneous or cutaneous form of infection, and 1 was from domestic dust). Candida parapsilosis ATCC 22019 and Candida krusei ATCC 6258 were used as control strains.The following 11 antifungal agents were tested by a microdilution method (18, 19): albaconazole (ABC), AMB, eberconazole (EBC), flucytosine (5FC), fluconazole (FLC), ITC, ketoconazole (KTC), micafungin (MFG), ravuconazole (RVC), terbinafine (TRB), and voriconazole (VRC).To convert S. schenckii into Y, the procedure was performed as described by Ghosh et al. (7). Mycelial cultures grown on potato dextrose agar (PDA) were subcultured on brain heart infusion agar supplemented with 5% defibrinated sheep blood at 37°C for approximately 6 to 9 days. Several successive passages were done to achieve Y. The suspensions were adjusted hemacytometrically, diluted 1:50, and further diluted 1:20 in RPMI to obtain double the final inoculum, which ranged from 1.0 ϫ 10 5 to 5.0 ϫ 10 5 CFU/ml. This inoculum was similar to that used by Nakai et al. schenckii from patients with cutaneous and disseminated sporotrichosis. Geometric means for panel A, disseminated, 2.13 g/ml; cutaneous, 0.63 g/ml (P ϭ 0.035, independent samples t test); geomet...

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A Pan-American 5-Year Study of Fluconazole Therapy for Deep Mycoses in the Immunocompetent Host

Cited by 126 publications

References 13 publications

An Open-Label Comparative Pilot Study of Oral Voriconazole and Itraconazole for Long-Term Treatment of Paracoccidioidomycosis

An Open-Label Comparative Pilot Study of Oral Voriconazole and Itraconazole for Long-Term Treatment of Paracoccidioidomycosis

Paracoccidioidomycosis: an update

In Vitro Antifungal Susceptibilities ofSporothrix schenckiiin Two Growth Phases

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