ライフサイエンスコーパス: echinocandin

1 ltidrug resistant to both fluconazole and an echinocandin.

2 tion between the antifungal triazole and the echinocandin.

3 isolates, 14.1% were resistant to 1 or more echinocandin.

4 and a newer class of antifungal agents, the echinocandins.

5 da species from WT strains using each of the echinocandins.

6 commonly used agents such as fluconazole and echinocandins.

7 ng the immunopharmacologic mode of action of echinocandins.

8 ple drug classes, including triazoles and/or echinocandins.

9 ntous fungi does not describe guidelines for echinocandins.

10 by the FKS genes, as the molecular target of echinocandins.

11 ds for strains exhibiting mid-range MECs for echinocandins.

12 the beta-1,3-glucan synthase, the target of echinocandins.

13 SI) in view of its reduced susceptibility to echinocandins.

14 y high MICs, except for voriconazole and the echinocandins.

15 major antifungal classes, the triazoles and echinocandins.

16 es that were resistant to one or more of the echinocandins (11.1% of all fluconazole-resistant isolat

17 luconazole, 35% to amphotericin B, and 7% to echinocandins; 41% were resistant to 2 antifungal classe

18 Of BSI isolates tested against the three echinocandins, 92, 99, and 100% were inhibited by concen

19 ith responses to cell wall stress induced by echinocandins, a front-line class of antifungal drugs.

20 Higher doses of echinocandins administered intermittently may be an alte

21 anted to expand our knowledge on the role of echinocandins against biofilm-related infections.

22 The activity of the echinocandins against Candida species known to express i

23 they are currently not suitable for testing echinocandins against Candida spp.

24 ting caspofungin acetate (MK-0991) and other echinocandins against molds.

25 cin B (AMB) and terbinafine (TRB) and of the echinocandins against Penicillium and Talaromyces specie

26 All three echinocandin agents currently available have been shown

27 We evaluated the new echinocandin aminocandin (AMN) for its antifungal activi

28 the emergence of in vitro resistance to the echinocandins among invasive Candida sp. isolates is ind

29 occurred in 7 patients (20%) treated with an echinocandin and in 15 (17.1%) treated with fluconazole

30 challenges to clinical success, followed by echinocandin and multidrug resistance among some Candida

31 ival and greater clinical success: use of an echinocandin and removal of the CVC.

32 trating intermediate or resistant MICs to an echinocandin and treated with an echinocandin failed to

33 We report the echinocandin and triazole antifungal susceptibility patt

34 Overall, echinocandin and triazole resistance rates were low; how

35 d in 17 (30%) of 57 patients who received an echinocandin and was more common in patients with FKS mu

36 s is important in determining R trends among echinocandins and Candida.

37 ggest inducement of beta-glucan unmasking by echinocandins and enhancement of PMN activity against mo

38 Novel antifungal agents, such as the echinocandins and the second-generation triazoles, were

39 The echinocandins and triazoles were active against Aspergil

40 andida isolates was observed for each of the echinocandins and varied by species.

41 ports of multidrug resistance to the azoles, echinocandins, and polyenes have occurred in several Can

42 ts but high activity overall for the azoles, echinocandins, and terbinafine.

43 ng the susceptibility of Candida spp. to the echinocandins anidulafungin, caspofungin, and micafungin

44 Resistance to echinocandins (anidulafungin [2.4%] and micafungin [1.9%

45 For each isolate, MICs to FLC and echinocandins (anidulafungin, caspofungin, and micafungi

46 ion (BSI) isolates of C. parapsilosis to the echinocandins, anidulafungin, caspofungin, and micafungi

47 All three echinocandins--anidulafungin (50% minimum effective conc

48 I, .35-.72; P = .0001) and treatment with an echinocandin antifungal (OR, 0.65; 95% CI, .45-.94; P =

49 Micafungin is an echinocandin antifungal agent that has recently been app

50 Caspofungin is a synthetic echinocandin antifungal agent that inhibits the synthesi

51 Anidulafungin is an echinocandin antifungal agent with potent activity again

52 The efficacy of anidulafungin, an echinocandin antifungal agent with potent anti-Candida a

53 increased potencies of the new triazole and echinocandin antifungal agents may provide effective the

54 The echinocandin antifungal caspofungin inhibits synthesis o

55 ivities of several of the newer triazole and echinocandin antifungals against isolates of C. dublinie

56 f reduced susceptibility to the triazole and echinocandin antifungals.

57 e systemically active antifungal agents, the echinocandins appear to be the most active against this

58 Echinocandins are a family of fungal lipidated cyclic he

59 Echinocandins are a group of antifungal agents that targ

60 The echinocandins are a small group of fungal N-acylated cyc

61 The echinocandins are being used increasingly as therapy for

62 The echinocandins are large lipopeptide molecules that are i

63 The echinocandins are large lipopeptide molecules that, sinc

64 Echinocandins are N-acyl-substituted cyclic hexapeptides

65 New therapeutic strategies using echinocandins are needed to improve clinical outcomes in

66 abrata resistant to both fluconazole and the echinocandins are of concern and prompted us to review t

67 FLC) resistance is common in C. glabrata and echinocandins are often used as first-line therapy.

68 In vitro and in vivo, the echinocandins are rapidly fungicidal against most Candid

69 Echinocandins are recommended for Candia glabrata candid

70 The echinocandins are relatively new antifungal drugs that r

71 Echinocandins are the recommended treatment for invasive

72 The echinocandins are widely distributed in the body, and ar

73 Limited data exist regarding echinocandins as antifungal prophylaxis in liver transpl

74 report here the biosynthetic gene cluster of echinocandin B 1 from Emericella rugulosa NRRL 11440 con

75 e antifungal agent cilofungin (LY121019), an echinocandin B analog.

76 htyA genes validate their essential roles in echinocandin B production.

77 We further analyzed the impact of echinocandin-based regimen as the initial antifungal the

78 The initial use of an echinocandin-based regimen does not seem to negatively i

79 analysis revealed that the initial use of an echinocandin-based regimen had any impact on the risk of

80 ral Candida spp. and the newer triazoles and echinocandins but are not yet available for older antifu

81 ynthase inhibitors, such as papulacandin and echinocandins, but no change in sensitivity to other ant

82 ole, ravuconazole, and voriconazole) and the echinocandin caspofungin acetate for 100 isolates of Can

83 a glabrata are now commonly treated with the echinocandins caspofungin (CSF) or micafungin (MCF).

84 three isolates from patients treated with an echinocandin (caspofungin) for which the MICs were > 2 m

85 Echinocandins (caspofungin, micafungin, and anidulafungi

86 Echinocandin CBPs are insensitive for detecting emerging

87 The echinocandin class of antifungal agents is considered to

88 and voriconazole and a representative of the echinocandin class of antifungal agents, MK-0991.

89 Caspofungin, a member of the new echinocandin class of compounds, may be an effective alt

90 ocandins are potent antifungal agents of the echinocandin class which are under development for use a

91 Echinocandins comprise a class of lipopeptide compounds

92 Azoles, polyenes and echinocandins constitute the mainstay of antifungal ther

93 rates were low; however, the fluconazole and echinocandin coresistance among C. glabrata strains warr

94 Whether echinocandins could be used to treat candidemia of a uri

95 rugulosa generates an echinocandin scaffold (echinocandin D) lacking both hydroxyl groups on Orn1.

96 The echinocandin derivative caspofungin (MK-0991, L-743,872)

97 en Histoplasma capsulatum, susceptibility to echinocandins differs for the yeast and the filamentous

98 Anidulafungin and the other echinocandins displayed sustained, excellent activity ag

99 Although echinocandins do not completely inhibit in vitro growth

100 In part because echinocandins do not induce clear growth inhibition end

101 The echinocandin drugs (micafungin, anidulafungin, and caspo

102 gene mutations responsible for resistance to echinocandin drugs was designed and evaluated.

103 lactic use of antifungal agents, such as the echinocandins, during periods of neutropenia or graft-ve

104 The echinocandin (ecd) gene cluster contains two predicted n

105 MICs of < or = 2 microg/ml for all three echinocandins encompass 98.8 to 100% of all clinical iso

106 Echinocandins exert in vitro and in vivo fungicidal acti

107 Micafungin is a new echinocandin exhibiting broad-spectrum activity against

108 es, a bimodal wild-type MIC distribution for echinocandins exists, but resistance to echinocandins is

109 ficant predictor for FKS mutations was prior echinocandin exposure (odds ratio [OR], 19.9; 95% confid

110 R, 4.7; 95% CI, 1.1-20.9; P = .04) and prior echinocandin exposure (OR, 8.3; 95% CI, 1.7-40.4; P </=

111 rs for FKS mutant isolates included previous echinocandin exposure, which also influenced response ra

112 MICs to an echinocandin and treated with an echinocandin failed to respond or responded initially bu

113 Echinocandin failure in C. glabrata is linked exclusivel

114 onclude that membrane sphingolipids modulate echinocandin-Fks interaction.

115 n institutions and susceptibility testing of echinocandins for C. glabrata to guide therapeutic decis

116 y contrast, the demonstrated efficacy of the echinocandins for the treatment of invasive aspergillosi

117 Neither echinocandin had in vitro activity (MICs, >16 microgram/

118 pecies tested) for the molds tested, but the echinocandins had a broader spectrum of fungicidal activ

119 Resistance to azoles and echinocandins has emerged as a significant factor affect

120 nt progress in the translational research of echinocandins has led to new approaches for treatment of

121 Anidulafungin, a new echinocandin, has potent activity against candida specie

122 e newer class of antifungal agents, known as echinocandins, has the potential to be useful in polymic

123 CBPs) for fluconazole, voriconazole, and the echinocandins have been revised to provide species-speci

124 All three echinocandins have excellent in vitro activities against

125 e investigated whether caspofungin and other echinocandins have immune-enhancing properties that infl

126 n that remains susceptible to the azoles and echinocandins; however, both the frequency of isolation

127 of coresistance over time to both azoles and echinocandins in clinical isolates of C. glabrata.

128 ended dosing intervals for administration of echinocandins in treatment and prevention of candidemia

129 the antifungal activity of micafungin, a new echinocandin, in combination with ravuconazole, a second

130 Resistance to echinocandins increased from 4.9% to 12.3% and to FLC fr

131 ss costly and less effective than ET with an echinocandin (incremental cost-effectiveness ratio, $111

132 Our experiments demonstrate that echinocandin-induced morphological changes in A. fumigat

133 ates susceptibility of enzymatic activity to echinocandin inhibition.

134 Previous studies suggested that echinocandin inhibitory activity is evident within 1 h o

135 Resistance to echinocandins is known to be caused by nonsynonymous mut

136 ffect, understanding the specific actions of echinocandins is paramount to optimizing their use at ei

137 for echinocandins exists, but resistance to echinocandins is rare.

138 beta(1-->3)glucan synthesis abolished by an echinocandin-like inhibitor, a strain carrying a wild-ty

139 he combination of an antifungal triazole and echinocandin may represent a new strategy for treatment

140 Limited clinical data suggest that echinocandins may have role to play in the treatment of

141 The new echinocandin micafungin has excellent in vitro activity

142 hods was achieved for all three FDA-approved echinocandins (micafungin, caspofungin, and anidulafungi

143 o the standard M27-A3 method for determining echinocandin MICs for Candida species.

144 mechanism contributes to the nonsusceptible echinocandin MICs in C. parapsilosis requires further st

145 The remaining isolates retained echinocandin MICs of <or=2 microg/ml and wild-type FKS g

146 Treatment response and echinocandin minimum inhibitory concentrations varied am

147 olates not susceptible to one or more of the echinocandins, most (68%) were C. guilliermondii.

148 versal of growth inhibition at high doses of echinocandins, most usually caspofungin.

149 equencing of fks hot spots was performed for echinocandin non-wild-type (WT) strains.

150 amphotericin B of > or = 1 microg/ml and of echinocandins of > or = 16 microg/ml, but they displayed

151 in-1 receptor, we investigated the effect of echinocandins on inflammatory responses to A. fumigatus.

152 ndidemia) in patients treated with either an echinocandin or fluconazole.

153 ficant change in the activities of the three echinocandins over the 6-year study period and no differ

154 herapy could become a general feature of the echinocandins, particularly for invasive aspergillosis.

155 Drugs in clinical development include echinocandins, pneumocandins, and improved azoles.

156 The echinocandins prevent fungal cell wall synthesis by inhi

157 The echinocandins provide a new therapy for Candida esophagi

158 review of this topic, evidence suggests that echinocandin-related cardiac dysfunction is a mitochondr

159 this population, such as the new azoles and echinocandins, remains to be determined.

160 rd of treatment of invasive candidiasis with echinocandins requires once-daily therapy.

161 Clinical echinocandin resistance among Candida glabrata strains i

162 surveillance reveals no evidence of emerging echinocandin resistance among invasive clinical isolates

163 We conclude that fks1 mutations that confer echinocandin resistance come at fitness and virulence co

164 utations in Candida albicans associated with echinocandin resistance has raised concerns over the spr

165 and FKS2 HS1 domains, which confer in vitro echinocandin resistance in C. glabrata isolates.

166 ctively detect the most common mechanisms of echinocandin resistance in C. glabrata within 4 h.

167 MIC of < or = 2 microg/ml due to the lack of echinocandin resistance in the population of Candida iso

168 Finally, clinical factors that promote echinocandin resistance include prophylaxis, host reserv

169 The mechanism of echinocandin resistance involves amino acid changes in "

170 clinical and molecular factors that promote echinocandin resistance is critical to develop better di

171 Echinocandin resistance is increasing, including among F

172 Overall echinocandin resistance was low (1% of isolates) but was

173 en the increase at both sites and the higher echinocandin resistance, C. glabrata should be closely m

174 e failed to detect C. glabrata isolates with echinocandin resistance-associated FKS2 mutations.

175 ctive way to screen C. glabrata isolates for echinocandin resistance.

176 the FKS1 and FKS2 genes are associated with echinocandin resistance.

177 K506 in combination with caspofungin against echinocandin resistant C. lusitaniae clinical isolates.

178 fungicidal activity with caspofungin against echinocandin resistant isolates.

179 In addition, we observed reduced fitness of echinocandin-resistant C. albicans in competitive mixed

180 Compared with wild-type strains for FKS1, echinocandin-resistant C. albicans strains with homozygo

181 Among echinocandin-resistant C. glabrata isolates from 2011, 3

182 The mutants were compared with C. albicans echinocandin-resistant mutants isolated by mutagenesis b

183 nts have many of the properties of FKS1/ETG1 echinocandin-resistant mutants of Saccharomyces cerevisi

184 st C. albicans strain SC5314 and its derived echinocandin-resistant mutants, which harbor an S645Y mu

185 By comparison, there were no echinocandin-resistant strains detected among 110 flucon

186 th prior surveillance; 32 (1%) isolates were echinocandin-resistant, and 9 (8 Candida glabrata) were

187 cing strain Emericella rugulosa generates an echinocandin scaffold (echinocandin D) lacking both hydr

188 In vitro, the echinocandins show potent antifungal activity against Ca

189 Although distinguishable by their echinocandin susceptibilities, all isolates from the cen

190 The CLSI clinical breakpoint (CBP) for echinocandin susceptibility (S; MICs of </= 2 mug/ml) ma

191 useful in surveillance for emerging reduced echinocandin susceptibility among Candida spp. and for d

192 amino acid residues known to be critical for echinocandin susceptibility in Saccharomyces are conserv

193 Echinocandins target fungal beta-1,3 glucan synthesis an

194 l clinical antifungals (azoles, allylamines, echinocandins) that target the ER or cell wall.

195 e availability of parenteral formulations of echinocandins, their synergy in murine models of mucormy

196 e predictor of a FKS mutant strain was prior echinocandin therapy (stepwise multivariable analysis, o

197 ariate nor multivariate analysis showed that echinocandin therapy altered the risk of clinical failur

198 itivity analyses determined that the cost of echinocandin therapy and the turnaround time for send-ou

199 Resistance to echinocandin therapy has been associated with FKS1 and F

200 Combination lipid polyene-echinocandin therapy is the most promising of such regim

201 Initial echinocandin therapy was not associated with clinical fa

202 come in patients with IC receiving primarily echinocandin therapy.

203 iological information of CUTS and to compare echinocandin to fluconazole treatment on CUTS outcomes.

204 ated with diminished beta-glucan exposure on echinocandin-treated germ tubes.

205 n contrast to treated conidia and germlings, echinocandin-treated hyphae stimulated increased release

206 no routine susceptibility testing with full echinocandin treatment course.

207 4; P </= .01) were independent predictors of echinocandin treatment failure.

208 C. neoformans cells are less susceptible to echinocandin treatment, we have cloned a homolog of S. c

209 No toxicity was observed with the echinocandin-triazole combination.

210 e DeltaecdK strain failed to generate mature echinocandin unless supplemented with either 4R-Me-Pro o

211 vidence that preemptive administration of an echinocandin was effective in preventing IC in high-risk

212 Among Candida spp., resistance to the echinocandins was low (0.0 to 1.7%).

213 Resistance to echinocandins was rarely found, occurring in only 0.2% o

214 r classes of drugs, such as the polyenes and echinocandins, was not affected by the presence of triaz

215 treatment outcomes in patients receiving an echinocandin were assessed using multivariate logistic r

216 All agents except for the echinocandins were active against C. neoformans, and the

217 e, posaconazole, voriconazole, and the three echinocandins were assessed against a recent (2011) glob

218 re the lowest, and the MICs of triazoles and echinocandins were higher than those of other antifungal

219 n [MEC90] range, 0.015 to 2 mug/ml), but the echinocandins were not active against other molds (MEC90

220 Overall, all three echinocandins were very active against Candida: anidulaf

221 proper cell cycle dynamics and responses to echinocandins, which inhibit beta-1,3-glucan synthesis.

222 mely broad antifungal spectra, and three are echinocandins, which inhibit synthesis of fungal cell wa

223 in combination antifungal therapy pairing an echinocandin with either an azole or amphotericin B form

224 The purified GS is inhibited by echinocandins with a sensitivity equal to that displayed

225 Excellent EAs were found for echinocandins with highly susceptible (MECs of <0.015 mu