Ambruticin represents a new class of antibiotics isolated from a strain of Polyangium cellulosum var. firlvum, a bacterium belonging to the class Myxobacteriales.This antibiotic is a cyclopropyl-polyene-pyran acid and is active in vitro against fungi.Myxobacteria are ubiquitous microorganisms found in soil, on the bark of trees , and on animal dung. These organisms are not detected by the routine methods used in culturing bacteria and fungi but require special techniques for their isolation1). In the course of our program to screen the Myxobacteriales as a source of biologically active compounds, an isolate of Polyangium cellulosum var. firlvum was found to have interesting antifungal properties. The present communication deals with the production and recovery of the antibiotic substances as well as the isolation and characterization of one of the antibiotics from this organism. Fourteen-liter capacity stir vessels (NBS FS-314) containing 10 liters fermentation medium were inoculated with seed culture (5-10 % v/v) and incubated at 32°C with 300 rpm agitation and sterile air supplied at 2 liters/minute through a single sparge hole. Peak titers occurred in -96 hours and harvested broths were pooled and stored at 4°C.Fermentation samples were monitored by a microbiological disc or cylinder-plate assay procedure using SABOURAUD dextrose agar and Microsporum fulvutn or Penicillium sp. (WLRI 0135) as the assay organism.* Proposed USAN

Ambruticin is a cyclopropyl-pyran acid, representing a new class of antibiotics. It has a relatively broad antifungal spectrum in vitro and is highly active against dimorphic as well as filamentous organisms. Of 24 strains of dermatophytic fungi tested, the majority were susceptible to ambruticin at 0.049 ug/ml or less. The minimal inhibitory concentration for the systemic fungi Histoplasma capsulatum and Blastomyces dermatitidis was 0.049 to 0.39 pg/ml. Ambruticin is fungicidal for metabolizing cells of Microsporum fulvum and does not cause cell leakage of 260-nm absorbing material. The antibiotic is effective orally as well as topically in guinea pigs experimentally infected with Trichophyton mentagrophytes. In mice, a single oral dose of 75 mg/kg produced peak serum levels of 45 pig/ml in 1 h with a serum half-life of 3.1 h. Excretion of the antibiotic is principally by the biliary route.

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The azoles are the prominent broad spectrum oral antifungal agents in use or under clinical investigation for the systemic mycoses. This class of antifungal agents is represented by the marketed drug ketoconazole (Nizoral) and the experimental triazoles furthest along in clinical trials in the United States, itraconazole and fluconazole. Ketoconazole use is limited by its side effect profile and activity spectrum. Itraconazole appears to be better tolerated and less toxic to liver function, does not cause adrenal suppression and is more active against Aspergillus and Sporothrix schenckii. Fluconazole appears to be a highly promising agent due its highly favorable pharmacokinetic profile; it is water soluble, is well tolerated, is not metabolized to inactive constituents, it has a long half-life and, unlike the other azoles, high cerebrospinal fluid levels are readily attained for consideration in meningeal mycoses. It remains to be determined what place these new triazoles have in managing immunosuppressed patients including those with acquired immune deficiency syndrome known as AIDS. Other experimental antifungal agents, including ambruticin, amphotericin B methyl ester and saramycetin are also described. Sales figures are presented of drugs marketed in the United States for the systemic mycoses and reflect the growing problem of fungal diseases in the population.

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