Efficacy of a Single 6 mg/kg versus Two 3 mg/Kg Caspofungin Doses for Treatment of Disseminated Candidiasis Caused byCandida albicansin a Neutropenic Mouse Model

Bayegan, Sedigh; Szilágyi, Judit; Kemény-Beke, Ádám; Földi, Richárd; Kardos, Gábor; Gesztelyi, Rudolf; Juhász, Béla; Adnan, Awid; Majoros, László

doi:10.1179/joc.2011.23.2.107

Cited by 3 publications

(2 citation statements)

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“…In the fungal tissue burden experiments BALB/c female mice (23–25 g) were given cyclophosphamide 4 days before infection (150 mg/kg), 1 day before infection (100 mg/kg), 2 and 5 days post-infection (100 mg/kg) 13,18,19. In the lethality experiments, this immunosuppression was continued by administration of 100 mg/kg cyclophosphamide every third day until the end of the experiment at the 21st day.…”

Section: Methodsmentioning

confidence: 99%

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Efficacy of humanized single large doses of caspofungin on the lethality and fungal tissue burden in a deeply neutropenic murine model against Candida albicans and Candida dubliniensis

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Tóth

Perlin

et al. 2019

IDR

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Background Echinocandins are the first-line therapy for treatment of invasive Candida infections, but the mortality rate remains high, calling for novel strategies. Giving single larger echinocandin doses infrequently is an alternative regimen. Our aim was to test this novel approach in a neutropenic murine model. Materials and methods We compared the in vivo efficacy of single 10 and 40 mg/kg of caspofungin (2.5× and 10× the normal humanized dose) to that of the same cumulative doses of daily 2 and 8 mg/kg doses for 5 days against 2 each of wild-type C. albicans and C. dubliniensis as well as echinocandin resistant C. albicans . As a comparator, we tested daily 1 mg/kg amphotericin B. Results In lethality experiments, all caspofungin and amphotericin B regimens improved survival against wild-type C. albicans and C. dubliniensis clinical isolates ( P <0.0001) and decreased the mean fungal kidney burdens of both species compared to controls. However, fungal kidney burden decreases were not always statistically significant, especially with single 10 or 40 mg/kg caspofungin doses. Amphotericin B was the least active drug against wild-type C. albicans . Against echinocandin-resistant strains, monodose 40 mg/kg caspofungin and 1 mg/kg of daily amphotericin B were effective in lethality experiments. Although, significant kidney CFU decreases were never found, except for amphotericin B against one of the isolates ( p <0.05 at day 3 and p <0.001 at day 6). Conclusion Single 40 mg/kg caspofungin and 1 mg/kg amphotericin B proved to be effective in the lethality experiments against wild-type and echinocandin-resistant C. albicans and wild-type C. dubliniensis . This was not always shown regarding fungal tissue burdens. Single caspofungin doses used in mice in this study are attainable in humans as well, suggesting a potential place of this dosing strategy not only in prevention but also in curative treatment of evolved invasive Candida infections.

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Section: Methodsmentioning

confidence: 99%

“…All groups were monitored twice daily for lethality 18. After 21 days, survival rate was analyzed by Kaplan–Meier test; the effect of different caspofungin doses and amphotericin B was compared using the logrank test 17–19…”

Section: Methodsmentioning

confidence: 99%

Efficacy of humanized single large doses of caspofungin on the lethality and fungal tissue burden in a deeply neutropenic murine model against Candida albicans and Candida dubliniensis

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Tóth

Perlin

et al. 2019

IDR

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Echinocandins: production and applications

Emri

Majoros

Tóth

et al. 2013

Appl Microbiol Biotechnol

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The first echinocandin-type antimycotic (echinocandin B) was discovered in the 1970s. It was followed by the isolation of more than 20 natural echinocandins. These cyclic lipo-hexapeptides are biosynthesized on non-ribosomal peptide synthase complexes by different ascomycota fungi. They have a unique mechanism of action; as non-competitive inhibitors of β-1,3-glucan synthase complex they target the fungal cell wall. Results of the structure-activity relationship experiments let us develop semisynthetic derivatives with improved properties. Three cyclic lipohiexapeptides (caspofungin, micafungin and anidulafungin) are currently approved for use in clinics. As they show good fungicidal (Candida spp.) or fungistatic (Aspergillus spp.) activity against the most important human pathogenic fungi including azole-resistant strains, they are an important addition to the antifungal armamentarium. Some evidence of acquired resistance against echinocandins has been detected among Candida glabrata strains in recent years, which enhanced the importance of data collected on the mechanism of acquired resistance developing against the echinocandins. In this review, we show the structural diversity of natural echinocandins, and we summarize the emerging data on their mode of action, biosynthesis and industrial production. Their clinical significance as well as the mechanism of natural and acquired resistance is also discussed.

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Comparison of In Vitro and Vivo Efficacy of Caspofungin Against Candida parapsilosis, C. orthopsilosis, C. metapsilosis and C. albicans

et al. 2012

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Caspofungin activity was determined in vitro and in vivo against three Candida orthopsilosis, three C. metapsilosis, two C. parapsilosis sensu stricto and two C. albicans isolates. MIC values and killing activity were determined in RPMI-1640 plus 50 % human serum. Neutropenic (cyclophosphamide-treated) mice were infected intravenously. Five-day intraperitoneal treatment with caspofungin was started after 24 h postinfection. Kidney burden was analyzed using the Kruskal-Wallis test with Dunn's post-test. In killing studies, caspofungin was fungistatic and fungicidal against C. albicans at ≥0.25 and ≥2 μg/ml concentrations, respectively. Caspofungin was fungistatic at ≥8-16, ≥2-8 and at ≥2-8 μg/ml against C. parapsilosis, C. orthopsilosis and C. metapsilosis, respectively. In the murine model, C. albicans was inhibited by 1, 2 and 5 mg/kg of caspofungin (P < 0.001 compared to the controls). Against C. parapsilosis, only 5 mg/kg caspofungin was effective against both isolates (P < 0.05). Two and five mg/kg of caspofungin was effective against all C. orthopsilosis and C. metapsilosis isolates (P < 0.05 to <0.001). Serum-based killing tests proved to be useful in predicting in vivo efficacy of caspofungin against four Candida species. Caspofungin at clinically attainable concentrations proved to be effective against all four species.

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Efficacy of a Single 6 mg/kg versus Two 3 mg/Kg Caspofungin Doses for Treatment of Disseminated Candidiasis Caused byCandida albicansin a Neutropenic Mouse Model

Cited by 3 publications

References 6 publications

<p>Efficacy of humanized single large doses of caspofungin on the lethality and fungal tissue burden in a deeply neutropenic murine model against <em>Candida albicans</em> and <em>Candida dubliniensis</em></p>

<p>Efficacy of humanized single large doses of caspofungin on the lethality and fungal tissue burden in a deeply neutropenic murine model against <em>Candida albicans</em> and <em>Candida dubliniensis</em></p>

Echinocandins: production and applications

Comparison of In Vitro and Vivo Efficacy of Caspofungin Against Candida parapsilosis, C. orthopsilosis, C. metapsilosis and C. albicans

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