Antimicrobial Activity of Econazole and Miconazole <i>in vitro</i> and in Experimental Candidiasis and Aspergillosis

Abstract

The antibacterial and antimycotic activity of econazole base, an imidazole derivative, was examined in vitro and in experimental infections of mice. Comparative minimal inhibitory concentration (MIC) determinations indicate econazole as well as miconazole to be of moderate activity against gram-positive bacteria (MICs: 0.78–25 μg/ml) and yeasts (MICs: 1.56–25 μg/ml). Against filamentous fungi, econazole exhibits better in vitro activity than miconazole and – with the exception of Rhizopus oryzae and Absidia corymbifera – MICs are markedly lower than against yeasts. No effect of nutrient media and no effect of the inoculum were observed with the four drugs. A strong influence of bovine serum on MIC values, however, suggested a strong protein binding. In experimental candidiasis of mice, no therapeutic effect with econazole base administered orally or intraperitoneally could be observed (ED₅₀ and ‘minimum life-prolonging dose’: > 200mg/kg). In experimental aspergillosis of mice, a slight effect, as demonstrated by the ‘minimum life-prolonging dose’ of 100 mg/kg, was found. The in vitro and in vivo results are discussed in the light of the available pharmacokinetic and toxicological data. It is concluded that more studies, especially on the pharmacology of econazole and about the clinical efficacy, are needed to come to a definite judgement.

Imidazole Antibiotics Inhibit the Nitric Oxide Dioxygenase Function of Microbial Flavohemoglobin

“…E. coli expressing a level of NOD activity of 116 Ϯ 12 nmol NO/min/ 10 8 cells was inhibited by 34 Ϯ 5, 41 Ϯ 3, and 24 Ϯ 3% following incubation with 50 M miconazole, econazole, and clotrimazole, respectively. The results are consistent with the poor membrane permeability and antibiotic activity of imidazoles toward gram-negative E. coli (3,48). By comparison, NO metabolism in gram-positive S. aureus was more sensitive to imidazole inhibition.…”

“…Azoles are widely used for treating various mycoses of skin, mucosa, and subcutaneous tissue. Ketoconazole, and more commonly itraconazole, and other potent triazole-based inhibitors of the lanosterol 14␣-demethylase are administered for systemic fungal infections (5,29,42,48,52,54,58). In addition, antifungal imidazoles show antibacterial activity (5,48,49,52,56,59), yet the antibiotic mechanisms remain to be fully elucidated.…”

Overview of medically important antifungal azole derivatives

“…Since econazole appears to be bound strongly by serum proteins, it is unsuitable for systemic therapy. The in vitro antifungal activity of econazole is comparable to that of miconazole; broad-spectrum activity against dermatophytes, Candida species, other pathogenic yeasts, filamentous fungi, and some gram-positive bacteria (26,202,255,303).…”

“…The drug was less effective in the treatment of aspergillosis (255) and coccidioidomycosis in the mouse (176). In the latter disease, for example, despite the fact that survival time was prolonged, cultures of organs remained positive.…”

Antifungal Activity of Tioconazole (UK-20,349), a New Imidazole Derivative

“…Some infections of the vagina and glabrous skin are treated satisfactorily by topical therapy with a variety of agents, and some dermatophyte infections are treated by oral therapy with griseofulvin (2, 10). The newer imidazole antifungal drugs, clotrimazole and miconazole, possess a very broad spectrum of antifungal activity (13,14,17,19,22), and resistance to them is rare (13). Their proven efficacy has led to their widespread acceptance for topical use (5,8,9,23).…”