Combination Therapy of Experimental Histoplasmosis and Cryptococcosis with Amphotericin Band Ketoconazole
68
Citation
9
Reference
10
Related Paper
Citation Trend
Abstract:
Combinations of amphotericin Band ketoconazole had an additive effect in vitro against Histoplasma capsulatum and Cryptococcus neoformans; ketoconazole combined with flucytosine exerted an indifferent effect against C. neoformans. In vivo studies in athymic nude (nu/nu) mice and their heterozygous (nu/ +) littermates demonstrated that treatment with the ketoconazole-amphotericin B combination resulted in longer survival of mice with cryptococcosis than did treatment with ketoconazole plus flucytosine. However, mice given ketoconazole plus amphotericin B did not survive significantly longer than those given amphotericin B alone (cryptococcosis) or ketoconazole alone (histoplasmosis). Combination chemotherapy with ketoconazole and amphotericin B may offer a modest therapeutic advantage over therapy with either drug alone.Keywords:
Flucytosine
The frequency of disseminated fungal infection in patients with the Acquired Immune Deficiency Syndrome (AIDS) has provided a major impetus for the reevaluation of standard antifungal protocols as well as accelerating the development and clinical testing of new agents. As a result, useful clinical guidelines regarding the use of amphotericin B and flucytosine in cryptococcosis are beginning to emerge that relate specifically to patients with AIDS. Oral agents, most notably fluconazole have shown promise and are now being evaluated in controlled clinical trials. Histoplasmosis and coccidioidomycosis have emerged as significant infections and pose new problems in both diagnosis and management. Although amphotericin B and flucytosine must still be used for induction therapy in patients with these infections, preliminary studies of itraconazole suggest that it could be useful for maintenance therapy. Despite there being considerably less clinical experience with histoplasmosis and coccidioidomycosis than with cryptococcosis, it is hoped that the lessons learnt with cryptococcosis will accelerate the development of new diagnostic assays and improved therapeutic approaches.
Flucytosine
Cite
Citations (10)
Summary The in vitro susceptibilities of Malaysian clinical isolates of Cryptococcus neoformans var. grubii and C . gattii to five antifungal drugs (amphotericin B, flucytosine, fluconazole, itraconazole and ketoconazole) were determined using the Etest method. None of the Malaysian isolates was resistant to amphotericin B and ketoconazole. Isolates resistant to flucytosine, fluconazole and itraconazole were observed in this study. Minimum inhibition concentrations (MICs) of ≥32 μ g ml −1 against flucytosine, ≥64 μ g ml −1 against fluconazole and ≥1 μ g ml −1 against itraconazole were noted in four (8.3%), two (4.2%) and one (2.1%) isolates respectively. There was no significant difference in the MICs for both Cryptococcus species ( P > 0.05), indicating that C. gattii was as susceptible as var. grubii to all the antifungal drugs tested. No significant difference in the MICs for both Cryptococcus species collected from 1980 to 1990 and 2002 to 2004 were observed ( P > 0.05).
Flucytosine
Cryptococcus gattii
Etest
Cite
Citations (29)
Objective To study the in vitro susceptibilities of Cryptococcus neoformans and Candida species collected from clinical samples (cerebrospinal fluid, sputum, urine and stool) to fluconazole, amphotericin B, itraconazole, 5 flucytosine and ketoconazole. The consistence of susceptibilities and clinical treatment efficacy was also evaluated. Methods 35 isolates of Cryptococcus neoformans and 56 isolates of Candida species were tested for their susceptibilities to five antifungal agents by broth microdilution method according to the National Committee of Clinical Laboratory Standard Recommendations (document M27 A). Results The susceptibilities of 56 isolates of Candida species to five antifungal agents were listed as follows: fluconazole 0.125～64 μg/ml , 94.6% of them were susceptible, 1.8% were dose dependent susceptible, 3.6% were resistant; itraconazole 0.03～1 μg/ml, 57.1% were susceptible, 37.5% were dose dependent susceptible, 5.4% were resistant; 5 flucytosine 0.125～32 μg/ml, 92.8% were susceptible, 3.6% were intermediate sensitive, 3.6% were resistant; amphotericin B 0.06～2 μg/ml, ketoconazole 0.03～0.5 μg/ml. The MIC ranges of 35 isolates of Cryptococcus neoformans were: fluconazole 2～ 64 μg/ml, itraconazole 0.25～1 μg/ml, amphotericin B 0.03～1 μg/ml, 5 flucytosine 0.25～64 μg/ml, ketoconazole 0.125 ～1 μg/ml.Conclusions The MICs of five antifungal drugs for Cryptococcus neoformans and Candida species obtained by the NCCLS M27 A method were consistent and could be reproduced.
Flucytosine
Broth microdilution
Cite
Citations (0)
A total of 53 Cryptococcus neoformans strains, including clinical and environmental Brazilian isolates, were tested for their susceptibilities to amphotericin B, 5-flucytosine, ketoconazole, fluconazole, and itraconazole. The tests were performed according to the National Committee of Clinical Laboratory Standards recommendations (document M27-P). In general, there was a remarkable homogeneity of results for all strains, and comparable MICs were found for environmental and clinical isolates. This paper represents the first contribution in which susceptibility data for Brazilian C. neoformans isolates are provided.
Flucytosine
Cite
Citations (54)
Combinations of amphotericin Band ketoconazole had an additive effect in vitro against Histoplasma capsulatum and Cryptococcus neoformans; ketoconazole combined with flucytosine exerted an indifferent effect against C. neoformans. In vivo studies in athymic nude (nu/nu) mice and their heterozygous (nu/ +) littermates demonstrated that treatment with the ketoconazole-amphotericin B combination resulted in longer survival of mice with cryptococcosis than did treatment with ketoconazole plus flucytosine. However, mice given ketoconazole plus amphotericin B did not survive significantly longer than those given amphotericin B alone (cryptococcosis) or ketoconazole alone (histoplasmosis). Combination chemotherapy with ketoconazole and amphotericin B may offer a modest therapeutic advantage over therapy with either drug alone.
Flucytosine
Cite
Citations (68)
Fungal infections figures large in HIV-infected patients. Candida infections of the mucous membranes belong to the main manifestations of immunodeficiency in HIV infection. For therapy and prophylaxis of oropharyngeal candidosis mainly systemically acting azoles as ketoconazole, fluconazole and itraconazole are applied; antimycotics to be administered topically regularly fail to act in patients with progressing disease. Ketoconazole tablets were used with good success in previous years of the AIDS epidemics. Application of ketoconazole in liquid formulation led to a significant increase in efficacy. Subsequently fluconazole proved to be a triazole with evidently better pharmacological properties leading to good clinical efficacy. Presently it represents the drug of first choice in acute and maintenance therapy of recurrent oropharyngeal and oesopharyngeal candidosis. In the case of therapy failure with fluconazole the administration of itraconazole in liquid cyclodextrine formulation can replace or at least delay the administration of amphotericin B plus flucytosine, a therapy rich in toxic side effects. The standard therapy of disseminated cryptococcosis--particularly of cerebral manifestation--is still the administration of amphotericin B combined with flucytosine. Alternative drugs are represented by fluconazole and itraconazole. However, an azole monotherapy seems to be legitimate only in primary cryptococcosis of the lungs or in early stages of secondary extrapulmonary infection. Cryptococcal meningitis requires an intense initial therapy. New therapy strategies were developed combining azoles with standard antimycotic drugs. The value of amphotericin B in liposomal or lipid complex formulations is still undetermined due to the up to now low number of AIDS patients treated.(ABSTRACT TRUNCATED AT 250 WORDS)
Flucytosine
Azole
Cite
Citations (7)
Abstract Susceptibility profiles of medically important fungi in less-developed countries remain uncharacterized. We measured the MICs of amphotericin B, 5-flucytosine, fluconazole, itraconazole, and ketoconazole for Cryptococcus neoformans clinical isolates from Thailand, Malawi, and the United States and found no evidence of resistance or MIC profile differences among the countries.
Flucytosine
Cite
Citations (54)
Flucytosine
Cite
Citations (14)
Flucytosine
Systemic candidiasis
Combination therapy
Cite
Citations (59)