J. Allan Waitz

KIJANIMICIN (Sch 25663), A NOVEL ANTIBIOTIC PRODUCED BY ACTINOMAD URA KIJANIATA SCC 1256

A novel antibiotic complex has been isolated form the fermentation broth of a new species of Actinomadura, A. kijaniata SCC 1256. The complex was separated form the broth by a solvent extraction procedure and consists of 1 major component, designated kijanimicin, and 3 minor components. Kijanimicin was isolated form the complex by column chromatography and/or preparative high pressure liquid chromatography. Structurally the compound is a unique, large acid enol antibiotic and possesses an unusual in vitro spectrum of activity against some Gram-positive and anaerobic microorganisms. In vivo it has also shown interesting activity against malaria.

Antibiotic G-418, a New Micromonospora-Produced Aminoglycoside with Activity Against Protozoa and Helminths: Antiparasitic Activity

Antibiotic G-418 was shown to be superior to paromomycin and metronidazole in cecal amoebiasis. Of particular interest was the high degree of activity seen with a relatively short treatment at low levels. Although the antibiotic was trichomonacidal in vitro at low levels, in vivo results indicated that at levels tested the antibiotic did not always affect cures. The antibiotic appears to have promise as an anticestode agent, being more active than paromomycin against Hymenolepis nana and active as a single oral dose at low levels against Taenia spp.

Interrelationships Between Disk and Tube Dilution Sensitivity Tests for the Aminoglycoside Antibiotics Gentamicin, Kanamycin, Sisomicin, and Tobramycin

Poor statistical correlation was obtained between tube dilution test results and disk test results by using standard procedures. Significant regressions were obtained although they were not linear. Different regressions were obtained with different bacterial species. It is suggested that for the aminoglycosides studied (gentamicin, kanamycin, tobramycin, and sisomicin) both disk and dilution tests are useful in separating resistant from sensitive organisms. However, poor relationships were obtained between the two test types among sensitive organisms.

Chapter 11. Antifungal Agents

Publisher Summary This chapter describes the synthesis and chemistry of antifungal agents. A review of the treatment of mycoses by use of antibiotics such as griseofulvin, nystatin, amphotericin B, pimaricin, 5-fluoro-cytosine, trichomycin, cycloheximide, clotrimazole, and miconazole covers the source of the antibiotic, chemistry, in vitro effects, clinical dosages, together with indications and side effects. A new animal model for acute oral candidiasis in rats may provide an additional system for the preclinical evaluation of new antifungal agents. Experimentally induced blastomycosis and histoplasmosis tend to mimic natural infections and are susceptible to amphotericin B therapy. Use of analog-resistant mutants to increase levels of end products, has been directed towards biosynthesis of pyrrolnitrins. β-Alanine has been shown to increase the yield of antifungal antibiotic AYF produced by Streptomyces aureofaciens . UV light and X-ray generate low-producing mutants as well as high producing mutants of Streptomyces nigrifaciens, with reference to antifungal production. Griseofulvin continues to be the main oral therapy for a number of dermatophyte infections and attempts to improve the speed and degree of absorption of griseofulvin following oral administration have continued. Dispersions of griseofulvin in a solid matrix of polyethylene glycol 6000, is demonstrated to lead to higher serum levels in man than those obtained with commercial micronized griseofulvin.

Chapter 13. Antifungal Agents

Publisher Summary This chapter presents an overview of some reviews that focus on antifungal agents. A review of pharmacokinetics of antifungal therapy included data on several systemic antifungals. Griseofulvin and clotrimazole were reviewed relative to their mechanism of action. Two reviews cover chemotherapy of mycoses, including most clinically useful antifungal agents, and hamycin, 5-fluorocytosine and clotrimazoles. Experimental dermatophyte infections in man are reviewed but therapeutic discussions are limited to griseofulvin and sodium omadine. A review related to problems in therapy and diagnosis of systemic candidiasis covers therapeutic evaluation of amphotericin B, 5-fluorocytosine, and clotrimazole. Side effects of intravenous amphotericin B therapy were evaluated; fever, chills, weakness, nausea, and nephrotoxicity were the prime consistent toxic manifestations. A series of 5,7-difluoro, dichloro, dibromo and diiodo quinolines, and 8 amino auinolhnes were prepared and tested for antifungal activity. The 5,7-difluoro derivative of quinoline was most active, while other halo derivatives were less active. Eight nitro quinolines showed greater activity than quinoline but halo substituted 8 nitro quinolines other than fluoro were less active. Amongst 8-aminoquinolines, all halo analogs were less active than the parent compounds.