Flucytosine—what is its future?

Viviani, M. A.

doi:10.1093/jac/35.2.241

Cited by 29 publications

(18 citation statements)

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“…Flucytosine would only rarely be used as monotherapy in humans, such as for urinary tract infections (27). However, studies of flucytosine in combination with several classes of antibiotics have shown that the pharmacodynamic parameter predictive of efficacy in combination therapy is the same as that observed with monotherapy (12,20).…”

Section: Discussionmentioning

confidence: 99%

In Vivo Characterization of the Pharmacodynamics of Flucytosine in a Neutropenic Murine Disseminated Candidiasis Model

Andes

Ogtrop

2000

Antimicrob Agents Chemother

121

137

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In vivo pharmacodynamic parameters have been characterized for a variety of antibacterial agents. These parameters have been studied in correlation with in vivo outcomes in order to determine (i) which dosing parameter is predictive of outcome and (ii) the magnitude of that parameter associated with efficacy. Very little is known of the pharmacodynamics of antifungal agents. We used a neutropenic murine model of disseminated candidiasis to correlate the pharmacodynamic parameters ( Groups of mice were treated with fourfold escalating total doses of 5-FC ranging from 1.56 to 400 mg/kg of body weight/day divided into one, two, four, or eight doses over 24 h. Increasing doses produced minimal concentration-dependent killing ranging from 0 to 0.9 log 10 CFU/kidneys. 5-FC did, however, produce a dosedependent suppression of growth after levels in serum had fallen below the MIC. The fungistatic dose increased from 6 to 8 mg/kg with dosing every 3 and 6 h to 70 mg/kg at with dosing every 24 h. Nonlinear regression analysis was used to determine which pharmacodynamic parameter best correlated with efficacy. Time above the MIC was the parameter best predictive of outcome, while AUC/MIC was only slightly less predictive (time above MIC, R 2 ‫؍‬ 85%; AUC/MIC, R 2 ‫؍‬ 77%; peak level/MIC, R 2 ‫؍‬ 53%). Maximal efficacy was observed when levels exceeded the MIC for only 20 to 25% of the dosing interval. If one considers drug kinetics in humans, these results suggest reevaluation of current dosing regimens.

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Section: Discussionmentioning

confidence: 99%

In Vivo Characterization of the Pharmacodynamics of Flucytosine in a Neutropenic Murine Disseminated Candidiasis Model

Andes

Ogtrop

2000

Antimicrob Agents Chemother

121

137

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“…Thus, 5FC has been used only in combination antifungal therapy [1,2,4]. Thus, 5FC has been used only in combination antifungal therapy [1,2,4].…”

Section: Introductionmentioning

confidence: 99%

Flucytosine Primary Resistance in Candida Species and Cryptococcus neoformans

Cuenca-Estrella

Diaz-Guerra

Mellado

et al. 2001

EJCMID

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The in vitro activity of flucytosine (5FC) against 1,140 clinical isolates of Candida spp. and Cryptococcus neoformans was evaluated and compared with the activity of amphotericin B, fluconazole and itraconazole. Overall, 87.72% (1,000/1,140) of yeasts were susceptible to 5FC. This agent showed less potent in vitro activity against Candida glabrata, Candida krusei, Candida guilliermondii and Cryptococcus neoformans (MIC90s, 8-16 microg/ml) and intermediate activity or resistance to 6.5% of Candida albicans, 5.1% of Candida tropicalis and 0.8% of Candida parapsilosis strains. Amphotericin B showed potent activity against isolates with an MIC of 5FC > or = 8 microg/ml. A total of 112 of 140 strains that were SFC-intermediate or -resistant showed decreased susceptibility to azoles (P < 0.01).

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“…The use of 5-FC is often made dif cult by development of secondary resistance in patients undergoing monotherapy [28][29][30][31]. Resistance may occur due to the de ciency or lack of enzymes involved in the uptake or metabolism of 5-FC, or may be due to disturbed regulation of the pyrimidine biosynthetic pathway, products of which can compete with the uorinated metabolites of 5-FC [32,33].…”

Section: Discussionmentioning

confidence: 99%

A flucytosine-resistantCryptococcus neoformans(serotype D) strain isolated in Turkey from cutaneous lesions

Kantarcıoğlu

Yücel²

2002

Med Mycol

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A Cryptococcus neoformans strain from cutaneous lesions of a patient with thrombotic thrombocytopenia purpura was tested for in vitro susceptibility against seven conventional antifungal agents. The strain was susceptible to fluconazole, itraconazole, ketoconazole and miconazole but was resistant to 5-fluorocytosine (5-FC). Minimal inhibitory concentration (MIC) values obtained against amphotericin B and terbinafine were 1 and 4 microg ml(-1), respectively. The isolate belonged to serotype D. Few human cases of cryptococcosis have been reported over the last 50 years in Turkey. This is the first C. neoformans isolate in Turkey shown to have primary resistance to 5-FC. Primary resistance to flucytosine is rarely reported in C. neoformans and may be associated with treatment failure in some cases.

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Flucytosine—what is its future?

Cited by 29 publications

References 0 publications

In Vivo Characterization of the Pharmacodynamics of Flucytosine in a Neutropenic Murine Disseminated Candidiasis Model

In Vivo Characterization of the Pharmacodynamics of Flucytosine in a Neutropenic Murine Disseminated Candidiasis Model

Flucytosine Primary Resistance in Candida Species and Cryptococcus neoformans

A flucytosine-resistantCryptococcus neoformans(serotype D) strain isolated in Turkey from cutaneous lesions

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