Caspofungin: An echinocandin antifungal agent

Stone, Elizabeth; Fung, Horatio B.; Kirschenbaum, Harold L.

doi:10.1016/s0149-2918(02)85039-1

Cited by 105 publications

(77 citation statements)

References 40 publications

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“…In other cases, the MIC value of a specific inhibitor fluctuate, depending on the method of analysis, the strain, or the organism. The MIC values of caspofungin described for C. albicans (0.0125-0.8 g/ml) and other Candida species (0.01-8.0 g/ml) are highly variable, although overall they denote a lower MIC compared with that obtained for S. pombe (11,23,49). This could be due to a lower susceptibility of Bgs4 or to a compensatory mechanism of the intrinsic resistant Bgs1 and Bgs3 subunits.…”

Section: Discussionmentioning

confidence: 90%

Differential Activities of Three Families of Specific β(1,3)Glucan Synthase Inhibitors in Wild-type and Resistant Strains of Fission Yeast

Martins¹,

Cortés²,

Muñoz³

et al. 2011

Journal of Biological Chemistry

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Three specific ␤(1,3)glucan synthase (GS) inhibitor families, papulacandins, acidic terpenoids, and echinocandins, have been analyzed in Schizosaccharomyces pombe wild-type and papulacandin-resistant cells and GS activities. Papulacandin and enfumafungin produced similar in vivo effects, different from that of echinocandins. Also, papulacandin was the strongest in vitro GS inhibitor (IC 50 10 3 -10 4 -fold lower than with enfumafungin or pneumocandin), but caspofungin was by far the most efficient antifungal because of the following. 1) It was the only drug that affected resistant cells (minimal inhibitory concentration close to that of the wild type). 2) It was a strong inhibitor of wild-type GS (IC 50 close to that of papulacandin). 3) It was the best inhibitor of mutant GS. Moreover, caspofungin showed a special effect for two GS inhibition activities, of high and low affinity, separated by 2 log orders, with no increase in inhibition. pbr1-8 and pbr1-6 resistances are due to single substitutions in the essential Bgs4 GS, located close to the resistance hot spot 1 region described in Saccharomyces and Candida Fks mutants. Bgs4 pbr1-8 contains the E700V change, four residues N-terminal from hot spot 1 defining a larger resistance hot spot 1-1 of 13 amino acids. Bgs4 pbr1-6 contains the W760S substitution, defining a new resistance hot spot 1-2. We observed spontaneous revertants of the spherical pbr1-6 phenotype and found that an additional A914V change is involved in the recovery of the wild-type cell shape, but it maintains the resistance phenotype. A better understanding of the mechanism of action of the antifungals available should help to improve their activity and to identify new antifungal targets.

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Section: Discussionmentioning

confidence: 90%

Differential Activities of Three Families of Specific β(1,3)Glucan Synthase Inhibitors in Wild-type and Resistant Strains of Fission Yeast

Martins¹,

Cortés²,

Muñoz³

et al. 2011

Journal of Biological Chemistry

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“…They act by inhibiting the synthesis of 1,3-b-D glucan, which is an important component of the fungal cell wall. 4,[7][8][9] Caspofungin (CAS) is the first antifungal agent in this new class. CAS has proven to be effective and well tolerated in the treatment of infections caused by Aspergillus spp, Candida albicans and non-C. albicans spp.…”

Section: Invasive Fungal Infectionmentioning

confidence: 99%

Caspofungin as second-line therapy for fever of unknown origin or invasive fungal infection following allogeneic stem cell transplantation

Trenschel

Ditschkowski

Elmaagacli

et al. 2005

Bone Marrow Transplant

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“…To overcome this problem and to improve the treatment outcome, advances have been made over the past decade in the fields of both diagnostics and therapeutics, including improvements in diagnostic imaging (7,8,18) and histopathology (1), and the development of broad-spectrum antifungal agents with low toxicities (4,24,29,33). In the field of diagnostics, much attention has recently been given to the development of several types of noninvasive laboratory tests for IA.…”

mentioning

confidence: 99%

Prospective Comparison of the Diagnostic Potential of Real-Time PCR, Double-Sandwich Enzyme-Linked Immunosorbent Assay for Galactomannan, and a (1→3)-β- d -Glucan Test in Weekly Screening for Invasive Aspergillosis in Patients with Hematological Disorders

Kawazu¹,

Kanda²,

Nannya³

et al. 2004

J Clin Microbiol

257

181

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The establishment of an optimal noninvasive method for diagnosing invasive aspergillosis (IA) is needed to improve the management of this life-threatening infection in patients with hematological disorders, and a number of noninvasive tests for IA that target different fungal components, including galactomannan, (133)-␤-D-glucan (BDG), and Aspergillus DNA, have been developed. In this study, we prospectively evaluated the diagnostic potential of three noninvasive tests for IA that were used in a weekly screening strategy: the double-sandwich enzyme-linked immunosorbent assay (ELISA) for galactomannan (Platelia Aspergillus), a real-time PCR assay for Aspergillus DNA (GeniQ-Asper), and an assay for BDG (␤-glucan Wako). We analyzed 149 consecutive treatment episodes in 96 patients with hematological disorders who were at high risk for IA and diagnosed 9 proven IA cases, 2 probable IA cases, and 13 possible invasive fugal infections. In a receiver-operating characteristic (ROC) analysis, the area under the ROC curve was greatest for ELISA, using

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Caspofungin: An echinocandin antifungal agent

Cited by 105 publications

References 40 publications

Differential Activities of Three Families of Specific β(1,3)Glucan Synthase Inhibitors in Wild-type and Resistant Strains of Fission Yeast

Differential Activities of Three Families of Specific β(1,3)Glucan Synthase Inhibitors in Wild-type and Resistant Strains of Fission Yeast

Caspofungin as second-line therapy for fever of unknown origin or invasive fungal infection following allogeneic stem cell transplantation

Prospective Comparison of the Diagnostic Potential of Real-Time PCR, Double-Sandwich Enzyme-Linked Immunosorbent Assay for Galactomannan, and a (1→3)-β- d -Glucan Test in Weekly Screening for Invasive Aspergillosis in Patients with Hematological Disorders

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