Inhibition and killing of Candida albicans in vitro by five imidazoles in clinical use

Lefler, Eli; Da, Stevens

doi:10.1128/aac.25.4.450

Cited by 40 publications

(17 citation statements)

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“…When susceptible strains were tested, discrepant results were the rule (29), although there are reports of spectrophotometric determination of 50% growth inhibition with very low MICs for most imidazoles (19), as we also found (Tables 1 and 2). Nevertheless, for the best-documented strains clinically resistant to KZ, most results indicated that the strains were cross-resistant in vitro to other azoles (17,25,33).…”

Section: Discussionsupporting

confidence: 61%

Patterns of in vitro activity of itraconazole and imidazole antifungal agents against Candida albicans with decreased susceptibility to fluconazole from Spain

Martı́nez-Suárez

Rodríguez-Tudela

1995

Antimicrob Agents Chemother

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Two groups of recent clinical isolates of Candida albicans consisting of 101 isolates for which fluconazole MICs were <0.5 g/ml (n ‫؍‬ 50) and >4.0 g/ml (n ‫؍‬ 51), respectively, were compared for their susceptibilities to fluconazole, clotrimazole, miconazole, ketoconazole, and itraconazole. Susceptibility tests were performed by a photometer-read broth microdilution method with an improved RPMI 1640 medium supplemented with 18 g of glucose per liter (RPMI-2% glucose; J. L. Rodríguez-Tudela and J. V. Martínez-Suárez, Antimicrob. Agents Chemother. 38:45-48, 1994). Preparation of drugs, basal medium, and inocula was done by the recommendations of the National Committee for Clinical Laboratory Standards. The MIC endpoint was calculated objectively from the turbidimetric data read at 24 h as the lowest drug concentration at which growth was just equal to or less than 20% of that in the positive control well (MIC 80%). In vitro susceptibility testing separated azole-susceptible strains from the strains with decreased susceptibilities to azoles if wide ranges of concentrations (20 doubling dilutions) were used for ketoconazole, miconazole, and clotrimazole. By comparison with isolates for which fluconazole MICs were <0.5 g/ml, those isolates for which fluconazole MICs were >4.0 g/ml were in general less susceptible to other azole drugs, but different patterns of decreased susceptibility were found, including uniform increases in the MICs of all azole derivatives, higher MICs of several azoles but not others, and elevated MICs of fluconazole only. On the other hand, decreased susceptibility to any other azole drug was never found among strains for which MICs of fluconazole were lower. Secondary resistance to azole antifungal agents in Candida albicans first appeared in the 1980s in patients with chronic mucocutaneous candidiasis treated with KZ for very long periods of time (25,33,36). The isolates involved had markedly reduced susceptibilities to KZ and cross-resistance to other azole drugs. More recently, resistance to the triazole FZ has been described in C. albicans strains isolated from the oral cavities of AIDS patients in different parts of the world (2, 5-8, 15, 18, 22, 24, 25, 28, 29, 32, 34, 36). The absence in most cases of comparative susceptibility data for alternative azole antifungal agents in these isolates still leaves open the question of whether cross-resistance to azole drugs in C. albicans is a general phenomenon.All of the azole antifungal agents share certain properties that makes in vitro susceptibility testing difficult, mainly partial inhibition of fungal growth that makes MIC endpoint determinations both very difficult and subjective (12,29,35). In the proposed standard of the National Committee for Clinical Laboratory Standards (NCCLS) (23), endpoints for azoles are determined visually at 48 h and the MIC is defined as the lowest drug concentration that reduces growth by 80% relative to the growth of the control (MIC 80%). We have previously shown that increased growth of C. albicans in RP...

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Section: Discussionsupporting

confidence: 61%

Patterns of in vitro activity of itraconazole and imidazole antifungal agents against Candida albicans with decreased susceptibility to fluconazole from Spain

Martı́nez-Suárez

Rodríguez-Tudela

1995

Antimicrob Agents Chemother

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“…It has a broad spectrum of activity and is more active than other imidazoles against Candida albicans in vitro (10,11,18). In a randomized study of 109 women with vaginal candidiasis, a 3-day course of treatment with 2% tioconazole vaginal cream produced higher cure rates 7 to 10 days (P = 0.01) and 4 weeks (P < 0.05) after therapy than did clotrimazole vaginal tablets (6).…”

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confidence: 99%

Single-dose tioconazole compared with 3-day clotrimazole treatment in vulvovaginal candidiasis

Stein¹,

Gurwith²,

Mummaw³

et al. 1986

Antimicrob Agents Chemother

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A total of 80 patients were equally randomized to receive a single dose of 6.5% tioconazole ointment or a 3-day course of 100-mg clotrimazole vaginal tablets for the treatment of vulvovaginal candidiasis. Of the 32 evaluable patients treated with tioconazole, 27 (84%) remained asymptomatic 4 weeks posttreatment, compared with 28 of 33 patients (85%) treated with clotrimazole. A total of 34 patients in each group could be evaluated for mycological response based on culture results 1 and 4 weeks after treatment. Twenty patients (59%) who received tioconazole and twenty-one patients (62%) who received clotrimazole remained culture negative 4 weeks after therapy. Of 40 patients who received tioconazole, 12 (30%) experienced local irritation or itching, compared with 2 of 40 patients (5%) treated with clotrimazole (P < 0.01). Single-dose tioconazole ointment was as effective as a 3-day course of clotrimazole tablets, but significantly more patients in the tioconazole-treated group experienced local side effects.The duration of treatment for Candida vaginitis has changed dramatically over the past several years. New high-dose imidazole derivatives have produced excellent short-term cure rates with treatment durations as short as 1 to 3 days (1,3,4,13,16,21). In addition, 4-week follow-up cultures of patients undergoing short-term treatment have not shown a higher incidence of recolonization by Candida organisms compared with cultures from patients undergoing longer periods of treatment (3,13,16,20,21). Shorter courses of therapy also encourage compliance and decrease expense and inconvenience (1,3,12,16).Tioconazole is a new imidazole antifungal agent similar to miconazole and clotrimazole. It has a broad spectrum of activity and is more active than other imidazoles against Candida albicans in vitro (10,11,18). In a randomized study of 109 women with vaginal candidiasis, a 3-day course of treatment with 2% tioconazole vaginal cream produced higher cure rates 7 to 10 days (P = 0.01) and 4 weeks (P < 0.05) after therapy than did clotrimazole vaginal tablets (6).Houang and Lawrence reported a mean vaginal concentration of 21.4 ,ug/ml 24 h after insertion of a single 300-mg ovule of tioconazole in 10 patients with vaginal candidiasis (8). This concentration is significantly higher than the MIC (1.6 to 12.5 ,ug/ml) of tioconazole for C. albicans (10). These studies suggest that a single application of the agent could be clinically effective in the treatment of Candida vaginitis.The study reported here was designed to compare the efficacy and acceptability of a single intravaginal application of 6.5% tioconazole ointment (325 mg) with a 3-day regimen of clotrimazole vaginal tablets in women with vulvovaginal candidiasis.(The study was presented in part at the 23rd Interscience Conference on Antimicrobial Agents and Chemotherapy, Las Vegas, Nev., 24 Before admission to the study, written informed consent was obtained from each patient. A medical history was taken, and a physical and gynecological examination, including a Pa...

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“…The extent and rapidity of this fungicidal effect of TCZ are greater than those of MCZ and clotrimazole. 9,10) This activity is paralleled by good topical efficacy in a guinea pig dermatomycosis model. 2,9) At the beginning, TCZ was been used as a cream formulation.…”

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confidence: 82%

Difference in Percutaneous Absorption and Intracutaneous Distribution in Guinea Pigs among Topical Antifungal Drugs (Tioconazole Solution, Tioconazole Cream, Miconazole Nitrate Solution and Bifonazole Solution)

Sobue

Sekiguchi

2004

Biological & Pharmaceutical Bulletin

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Tioconazole (TCZ) is an imidazole antifungal agent with broad spectrum activity in vitro against dermatophytes and yeasts, as well as against some chlamydia, trichomonads and Gram-positive bacteria.1,2) Its in vitro antifungal activity against dermatophytes, yeasts and bacteria is equal or stronger in comparison with those of the known imidazoles, miconazole nitrate (MCZ), bifonazole (BFZ) and clotrimazole. [3][4][5] TCZ has a dual mechanism of antifungal action that is inhibition of sterol biosynthesis and direct cell membrane damage. [6][7][8] In growing cultures, TCZ exerts a potent killing action. The extent and rapidity of this fungicidal effect of TCZ are greater than those of MCZ and clotrimazole. 9,10) This activity is paralleled by good topical efficacy in a guinea pig dermatomycosis model. 2,9) At the beginning, TCZ was been used as a cream formulation. Clinical trials for treating superficial dermatophyte or yeast infections of the skin have clearly demonstrated once to three times a day topical applications of TCZ cream were at least as effective as alternative imidazole antifungal drugs, and in a few trials significantly greater efficacy has been reported for TCZ cream, compared with MCZ, clotrimazole, and econazole. 1,[11][12][13][14] After that TCZ solution was developed as over-the-counter drug. The efficacy and safety of twice or three times a day topical preparations of TCZ solution appear to be similar to those of TCZ cream and clotrimazole solution. [15][16][17][18] Pharmacokinetic studies in rats have demonstrated minimal systemic exposure following dermal application of TCZ cream.2) After a single application of TCZ cream about 16% of the applied radioactivity penetrates into rat skin and the percutaneous penetration into swine skin is considerably higher than that of clotrimazole cream.19) BFZ also penetrates far better into human skin than clotrimazole. 20) Clinical trials have clearly demonstrated the efficacy and safety of various formulations of BFZ applied once a daily in the treatment of superficial fungal infections of the skin.4) The skin retention time of MCZ in effective therapeutic concentrations is longer than that of BFZ. MCZ formulations are also recommended for once a daily application. 21) In the present study, in order to support the usefulness of once a daily applications of TCZ solution and cream, the percutaneous absorption and intracutaneous distribution of TCZ solution were investigated and compared with those of TCZ cream, MCZ solution and BFZ solution following a single topical application to abdominal skin of guinea pigs. (Tokyo, Japan). Itraconazole, IS for BFZ, was extracted from commercial preparations purchased from Janssen Kyowa Co., Ltd. (Tokyo, Japan). All other chemicals used were of reagent grade. MATERIALS AND METHODS MaterialsAnimals Guinea pigs of the Hartley strain (Japan SLC, Shizuoka, Japan) weighing approximately 400 g were used in the study. The animals were kept in an animal room main- Tioconazole (TCZ) is an imidazole antifungal agent with broa...

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Inhibition and killing of Candida albicans in vitro by five imidazoles in clinical use

Cited by 40 publications

References 19 publications

Patterns of in vitro activity of itraconazole and imidazole antifungal agents against Candida albicans with decreased susceptibility to fluconazole from Spain

Patterns of in vitro activity of itraconazole and imidazole antifungal agents against Candida albicans with decreased susceptibility to fluconazole from Spain

Single-dose tioconazole compared with 3-day clotrimazole treatment in vulvovaginal candidiasis

Difference in Percutaneous Absorption and Intracutaneous Distribution in Guinea Pigs among Topical Antifungal Drugs (Tioconazole Solution, Tioconazole Cream, Miconazole Nitrate Solution and Bifonazole Solution)

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