Effect of cilofungin on phagocytosis and intracellular killing ofCandida albicans by human neutrophils

Richardson, Malcolm; Scott, G. D.; Shankland, G. S.

doi:10.1007/bf01971266

Cited by 12 publications

(21 citation statements)

References 14 publications

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“…The majority of systemic antifungal drugs do not significantly influence the phagocytic activity of PMNs against Candida spp. (8,13,14). We reported that fluconazole enhances the in vitro killing activity of phagocytes against C. albicans, without improving phagocytosis (18,19).…”

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confidence: 99%

Synergy of Caspofungin with Human Polymorphonuclear Granulocytes for Killing Candida albicans

Tullio

Mandras

Scalas

et al. 2010

Antimicrob Agents Chemother

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The influence of caspofungin on polymorphonuclear leukocyte (PMN) phagocytosis and intracellular killing of Candida albicans was investigated. Caspofungin, at all of the concentrations tested (2, 3.2, and 8 g/ml), significantly increased intracellular killing by PMNs through its direct action on both yeast cells and PMNs, indicating the potential ability of caspofungin to synergize with phagocytes for candidal killing. Caspofungin may therefore constitute an effective therapeutic option for the treatment of invasive fungal infections, including those refractory to conventional treatment with azole agents.Echinocandins, such as caspofungin, are new drugs that broaden the available therapeutic arsenal for invasive fungal infection (IFI) treatment (6,7,11). Caspofungin displays favorable pharmacodynamic and pharmacokinetic characteristics and has an excellent toxicological profile and antifungal activity against Candida spp., Aspergillus spp., Histoplasma spp., Blastomyces spp., and Coccidioides spp. (3,7,11,12,15). As the current trend in therapy requires drugs with high in vitro activity associated with the capacity to potentiate host defense mechanisms, especially in immunocompromised hosts (2, 19), the interaction of caspofungin with human polymorphonuclear leukocytes (PMNs) was evaluated, focusing on both the phagocytosis and intracellular killing of Candida albicans.(This study was presented in part at the Congress of the Italian Society of Pharmaceutical Microbiology, Turin, Italy, 20 to 22 June 2008.)A clinical C. albicans strain isolated from blood and identified by biochemical methods was subcultured on Sabouraud dextrose agar (Oxoid S.p.A., Milan, Italy) to ensure viability and purity. Yeast cultures consisted entirely of blastoconidia and had a slight tendency to differentiate into pseudohyphae during the course of the experiments.Caspofungin acetate (Merck Sharp & Dohme Ltd., Hoddesdon, United Kingdom) was dissolved in pyrogen-free water and stored at Ϫ20°C. Antifungal susceptibility testing was performed with an inoculum of 10 3 CFU/ml, in accordance with CLSI M27-A3 (4), and an inoculum of 10 6 CFU/ml was used to perform tests with phagocytes.PMNs were separated from lithium heparinized venous blood using Ficoll-Paque (Pharmacia S.p.A., Milan, Italy) and adjusted to 10 6 cells/ml in RPMI 1640 medium (Gibco Laboratories, Grand Island, NY) (1, 5). Viability, determined by trypan blue exclusion, was greater than 95%.The effect of caspofungin on the phagocytosis of radiolabeled C. albicans ([ 3 H]uracil [specific activity, 1,270 GBq/ mmol; NEN Life Science Products, Milan, Italy]) by PMNs was investigated by incubating the yeast cells (10 6 invasive fungal cells/ml) and PMNs (10 6 cells/ml) at 37°C in a shaking water bath in the presence of 2 g/ml (MIC), 3.2 g/ml, or 8 g/ml caspofungin; the last two concentrations were within the range achieved clinically (8, 9). Caspofungin-free controls were included. After 30, 60, or 90 min, phagocytosis was assessed (18,19). PMNs were centrifuged twice at 200 ϫ g fo...

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confidence: 99%

Synergy of Caspofungin with Human Polymorphonuclear Granulocytes for Killing Candida albicans

Tullio

Mandras

Scalas

et al. 2010

Antimicrob Agents Chemother

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“…Fluconazole, too, is of assistance in this regard. Other antifungal agents, such as amphotericin B and cylofungin, interact with various cell mechanisms and promote an immune response [28,29]. Fluconazole does not inhibit T cell proliferation, cytokine secretion (i.e.…”

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confidence: 99%

Combined effect of fluconazole and thymosin α1 on systemic candidiasis in mice immunosuppressed by morphine treatments

Francesco

Gaziano

Casalinuovo

et al. 1994

Clinical and Experimental Immunology

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SUMMARY Treatment of systemic infection with Candida albicans with a combination of an antifungal agent (i.e. fluconazole) and a thymus‐derived immunostimulant (i.e. thymosin α1 (Tal)) in mice immunosuppressed by morphine treatments was investigated. In normal mice, fluconazole given after infection with 106 C. albicans cells was more effective than in mice treated with morphine. Combination treatment with fluconazole and Tal prolonged survival and reduced the fungal burden in the kidneys of immunosuppressed mice. We also investigated the influence of this combined treatment on killing properties of polymorphonuclear leucocytes (PMN) and natural killer (NK) cell activity, inhibited by morphine administrations. Treatment with TQI or fluconazole as single agents promoted a recovery of normal NK cell activity and intracellular killing of C. albicans by PMN, while the combination significantly increased both of these responses, probably through the modulation of lymphokine production. Our data suggest that the additive effect of T α 1 and fluconazole is due lo a direct antifungal action and activation of the immunocompetence.

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“…İnkübasyonun sonunda üreyen maya kolonilerinden, Sabouraud Dextrose Broth (SDB) (Merck) besiyerine tekrar pasaj yapılmış ve 24 saat 37 0 C'de inkübe edilmiştir. İnkübasyonun bitiminde, deneylere başlamadan 1 saat önce bu pasajda üreyen maya kültüründen SDB besiyerine tekrar pasaj yapıl-mış ve 37 0 C'de 1 saat inkübe edilmiştir (18,19). Sonraki aşama-da 1 saatlik bu kültür, besiyeri bileşenlerinin maya hücrelerin-den uzaklaştırılması için 2000 rpm'de 10 dakika santrifüj edilerek 2 kez FTS ile yıkanmıştır.…”

Section: Polimorf Nüveli Lökositler (Pnl)'in Elde Edilmesiunclassified

Bronşektazili hastalarda kolistinin tek başına ve tigesiklin, imipenem ve rifampisin ile kombinasyonlarının polimorf nüveli lökosit fonksiyonları, oksidatif stres, oksidan ve antioksidan enzimler üzerine etkilerinin in vitro araştırılması

Gürbüz¹,

Gürer²,

Çevik³

et al. 2014

Marmara Pharm J

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GİRİŞBronşektazi, bronş duvarının anormal, geri dö-nüşümsüz dilatasyonu ile seyreden kronik inflamatuvar bir hastalıktır. Antibiyotik kullanımı ve aşı uygulamaları sonucu, gelişmiş ülkelerde bronşektazi insidansı azalmakta iken, gelişmekte olan ülkelerde etkin aşılama yapılamaması, tekrarlayan, iyi tedavi edilemeyen alt solunum yolu enfeksiyonları ve yüksek akciğer tüberkülozu prevalansı nedeniyle hala yaygın bir hastalık olarak görülmektedir (1,2,3).Bronşektazili hastaların akut ataklarının tedavisinde, atakların önlenmesinde veya bakteriyel birikimi azaltmak için kullanılan antibiyotikler; oral, intravenöz veya inhalasyon yoluyla uygulanabilir. Genel olarak antibiyotiklerle tedavi sonuçları hastalığın şiddetine bağlıdır. Hafiften ortaya bronşektazili infeksiyonlarda tamamen eradikasyon sağlanabilir. Ancak şiddetli hastalığı olanlarda bronşiyal ağaçta kronik olarak kolonizasyon kalabilir (4).Bakteriler solunum yoluna yerleştikten sonra oluşan inflamasyonda en sık görülen hücreler polimorf nüveli lökositler (PNL) dir. İnflamasyon bölgesine toplanan PNL'lerden serbest oksijen radikalleri (SOR = Oksidanlar) salınması doku hasarına neden olmaktadır. Ayrıca P. aeruginosa'nın etken olduğu infeksiyonlarda bakteriye ait proteazların da ortama katılmasıyla bronş sıvısındaki IgG'lerin %80'inden fazlasının ÖZET: Çalışmamızda, terapötik konsantrasyonlarda kolistinin (4 μg/ml) tek başına ve tigesiklin (0.87 μg/ml), imipenem (30 μg/ml) ve (rifampisin (7 μg/ml) ile kombinasyonlarının bronşektazili hastaların polimorf nüveli lökosit (

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Effect of cilofungin on phagocytosis and intracellular killing ofCandida albicans by human neutrophils

Cited by 12 publications

References 14 publications

Synergy of Caspofungin with Human Polymorphonuclear Granulocytes for Killing Candida albicans

Synergy of Caspofungin with Human Polymorphonuclear Granulocytes for Killing Candida albicans

Combined effect of fluconazole and thymosin α1 on systemic candidiasis in mice immunosuppressed by morphine treatments

Bronşektazili hastalarda kolistinin tek başına ve tigesiklin, imipenem ve rifampisin ile kombinasyonlarının polimorf nüveli lökosit fonksiyonları, oksidatif stres, oksidan ve antioksidan enzimler üzerine etkilerinin in vitro araştırılması

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