Miconazole in Coccidioidomycosis. I. Assays of Activity in Mice and in Vitro

Levine, Howard B.; Stevens, David A.; Cobb, J.M.; Gebhardt, A. E.

doi:10.1093/infdis/132.4.407

Cited by 76 publications

(33 citation statements)

References 13 publications

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“…Van Cutsem and Thienpont (323) demonstrated the efficacy of miconazole given orally or topically against cutaneous infections with T. mentagrophytes, Microsporum canis, and C. albicans in guinea pigs. In another study, all mice given miconazole intramuscularly and subcutaneously 4 days after infection with 50 or 100% lethal doses of Coccidioides immitis were protected, whereas 60 to 100% of the untreated mice succumbed (178). Cultural assays of lung tissue confirmed that the drug limited proliferation of the fungus at that site.…”

Section: Clotrimazolementioning

confidence: 95%

Overview of medically important antifungal azole derivatives

1988

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Fungal infections are a major burden to the health and welfare of modern humans. They range from simply cosmetic, non-life-threatening skin infections to severe, systemic infections that may lead to significant debilitation or death. The selection of chemotherapeutic agents useful for the treatment of fungal infections is small. In this overview, a major chemical group with antifungal activity, the azole derivatives, is examined. Included are historical and state of the art information on the in vitro activity, experimental in vivo activity, mode of action, pharmacokinetics, clinical studies, and uses and adverse reactions of imidazoles currently marketed (clotrimazole, miconazole, econazole, ketoconazole, bifonazole, butoconazole, croconazole, fenticonazole, isoconazole, oxiconazole, sulconazole, and tioconazole) and under development (aliconazole and omoconazole), as well as triazoles currently marketed (terconazole) and under development (fluconazole, itraconazole, vibunazole, alteconazole, and ICI 195,739).

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Section: Clotrimazolementioning

confidence: 95%

Overview of medically important antifungal azole derivatives

1988

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“…immitis strain Silveira (ATCC 28868), that has been used in many previous studies (2,14,17). However, it is reasonable to monitor periodically the serum levels of amB in patients with coccidioidomycosis so that the intravenous dosage can be adjusted to provide serum levels of 1.0 to 2.0 ug/ml, which appears to suffice for inhibition of C. immitis.…”

Section: Discussionmentioning

confidence: 99%

“…coccidioidomycosis, though recent work has indicated that miconazole may assume a position of some importance (5, 17,31,32). The effectiveness of amB in treating various forms of disseminated coccidioidomycosis of humans has been difficult to assess precisely, though it has proved lifesaving in coccidioidal meningitis.…”

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confidence: 99%

Uniform Susceptibility of Various Strains of Coccidioides immitis to Amphotericin B

Collins

Pappagianis

1977

Antimicrob Agents Chemother

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The susceptibility of 12 strains of Coccidioides immitis to amphotericin B. (amB) was studied in vitro and in vivo. The minimal inhibitory concentration (MIC) of the mycelial phase of these strains was 0.078 to 0.16 ,ug/ml after 3 days of incubation, but by 15 days all strains were inhibited by 2.5 ,ug/ml. Mice infected intraperitoneally with these strains were sucessfully treated with 0.5 mg of amB per kg per day. These strains included several studied by others and which reportedly varied widely in susceptibility (MIC from 0.24 to 24.01 ,ug/ml) to amB. Four of these strains representing this putative broad range of susceptibility were used to infect mice intranasally. Regardless of infecting strain, mice were sucessfully treated with 0.38, 0.75, and 1.5 mg/kg, but 0.19 mg/kg was only partially effective. Thus, in vivo as well as in vitro there was a uniform response of C. immitis strains to amB.

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“…Because of these favorable properties, ketoconazole is currently undergoing clinical investigation in a number of medical centers. A method which has been used for measurement of ketoconazole in serum and other body fluids is tedious and hazardous to perform due to the use of Coccidioides immitis as a test microorganism (3). The present report describes a rapid, simple, very sensitive bioassay for the measurement of ketoconazole in serum, cerebrospinal fluid, and other body fluids alone or in the presence of amphotericin B. several times; then the seeded medium was dispensed into plastic petri dishes (150 by 15 mm) arranged on a level surface.…”

mentioning

confidence: 99%

Sensitive bioassay for ketoconazole in serum and cerebrospinal fluid

Jorgensen¹,

Alexander²,

Graybill³

et al. 1981

Antimicrob Agents Chemother

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Ketoconazole is a broad-spectrum antifungal agent which appears promising for treatment of a variety of systemic mycoses. Pharmacokinetic studies are limited due to a lack of readily available methods for quantitation of ketoconazole in serum or cerebrospinal fluid. We developed a rapid, simple bioassay for measurement of ketoconazole alone or in the presence of therapeutic levels of amphotericin B, using an agar diffusion assay incorporating Candida pseudotropicalis. Pairs of 8-mm wells cut in the seeded assay medium were filled with four duplicate ketoconazole standards and duplicate patient specimens. Zones of inhibition were visible after 7 to 8 h of incubation, but were most easily measured after overnight growth. The assay allowed determinations of serum ketoconazole levels as low as 0.3 ,ug/ml with a 4.4% coefficient of variation. Thirty-five serum samples from patients receiving the drug were assayed by this method, and the results were compared with the Coccidioides immitis endospore assay. The correlation coefficient between the assays was 0.90. This assay allows any microbiology laboratory to easily and safely determine ketoconazole levels in serum or cerebrospinal fluid.

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Miconazole in Coccidioidomycosis. I. Assays of Activity in Mice and in Vitro

Cited by 76 publications

References 13 publications

Overview of medically important antifungal azole derivatives

Overview of medically important antifungal azole derivatives

Uniform Susceptibility of Various Strains of Coccidioides immitis to Amphotericin B

Sensitive bioassay for ketoconazole in serum and cerebrospinal fluid

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