Amphotericin B and amphotericin B methyl ester ascorbate. I. Chemotherapeutic activity against Candida albicans, Cryptococcus neoformans, and Blastomyces dermatitidis in mice.

Amphotericin B methyl ester (AME) has been reported to possess in vitro antifungal activity similar to that of amphotericin B and to have less intrinsic toxicity in mice and dogs. For these reasons AME has been porposed as an alternative to amphotericin B in the therapy of deep mycoses. For comparison of the therapeutic efficacy of the two polyenes in laboratory animals before initiation of studies in humans, groups of mice were infected with Candida albicans, Cryptococcus neoformans, and Blastomyces dermatitidis. Treatment consisted of two or more doses of each drug given by the intravenous route. Concurrently, studies of subacute toxicity were conducted in the same species to permit calculation of therapeutic indices. These studies have shown that AME, as the ascorbate salt, is substantially less efficacious than amphotericin B (in colloidal dispersion with sodium deoxycholate) for treatment of the fungal infections and that amphotericin B had a higher therapeutic ratio for all infections studied than did AME.

New antimicrobial nitrofuran, trans-5-amino-3-[2-(5-nitro-2-furyl)vinyl]-delta2-1,2,4-oxadiazole: antimicrobial efficacy in mice, rats, and guinea pigs.

A new antimicrobial nitrofuran designated SQ 18,506 showed some therapeutic activity when administered orally to mice infected with Escherichia coli, Salmonella schottmuelleri, Shigella flexneri, or Klebsiella pneumoniae. Animals infected parenterally with Streptococcus pyogenes, Proteus mirabilis, Mycobacterium tuberculosis, and Candida albicans, or topically with Trichophyton mentagrophytes, did not respond to therapy with the drug at the dosage levels used. The compound was as effective as metronidazole in the topical treatment of experimental trichomonal infections in mice and in guinea pigs and as effective as nystatin, candicidin, or a sulfanilamide-aminacrine hydrochloride cream in the treatment of a candidal vaginal infection in rats. The chemotherapeutic efficacy of SQ 18,506 in experimental vaginitis caused by Escherichia coli in the rat surpassed that shown by four commercial products available for the treatment of bacterial vaginitis.

Epicillin: experimental chemotherapy, pharmacodynamics, and susceptibility testing.

Epicillin exhibits excellent therapeutic activity when administered orally or subcutaneously to mice infected with a variety of pathogenic bacteria. These included single strains of Streptococcus pyogenes, non-penicillinase-producing Staphylococcus aureus, Proteus mirabilis, Escherichia coli, Salmonella schottmuelleri, and Pseudomonas aeruginosa, strains of microorganisms selected as typical of those that frequently cause serious clinical infections. In oral chemotherapeutic comparisons of tetracycline, chloramphenicol, cephalexin, ampicillin, and epicillin, the latter, with but minor exceptions, exhibited activity comparable to that of most of the other antibiotics studied. Oral administration to mice of a loading dose of epicillin or ampicillin resulted in similar peak blood levels and decay curves. The concentration in urine and the excretion rates were significantly higher in epicillin than in ampicillin-treated animals. Presumptive evidence suggests that the inter-pretation of zone diameters obtained with 10-mug epicillin discs should be the same as is used for 10-mug ampicillin discs.

Biological characterization of prasinomycin, a phosphorus-containing antibiotic.

Prasinomycin, a new antibiotic from the green spore streptomycete, Streptomyces prasinus, primarily inhibits the growth of gram-positive microorganisms. Like penicillin, it is effective only against growing cells. Though primarily bacteriostatic at levels about the minimal inhibitory concentration, it is bactericidal at higher levels. Neither synergism nor antagonism could be demonstrated for prasinomycin with a variety of other antibiotics. It is highly active upon subcutaneous administration to mice infected with Staphylococcus aureus, Streptococcus pyogenes C203, or Diplococcus pneumoniae. Prasinomycin has a unique prophylactic action whereby one dose protects mice against experimental infections for as long as 2 months. It is more effective against S. aureus infections in mice when administered subcutaneously 20 hr prior to infection than when given in divided doses 1 hr before and 4 hr after infection.