ライフサイエンスコーパス: echinocandin

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

2 ltidrug resistant to both fluconazole and an echinocandin.

3 tion between the antifungal triazole and the echinocandin.

4 rezafungin is noninferior to the comparator echinocandin.

5 clusters are recognized as relatives of the echinocandins.

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

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

8 commonly used agents such as fluconazole and echinocandins.

9 ng the immunopharmacologic mode of action of echinocandins.

10 ntous fungi does not describe guidelines for echinocandins.

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

12 0%) isolates, were susceptible to comparator echinocandins.

13 atment, but recent guidelines also recommend echinocandins.

14 ffer markedly in their adaptive responses to echinocandins.

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

16 use it exhibits self-resistance to exogenous echinocandins.

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

18 tected, while few isolates were resistant to echinocandins.

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

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

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

22 major antifungal classes, the triazoles and echinocandins.

23 tericin B (61%), flucytosine (5FC) (3%), and echinocandins (1%).

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

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

26 dins, while FLZS-CP patients received either echinocandins (60.5%) or fluconazole (39.5%).

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

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

29 As C. parapsilosis IE was not treated with echinocandins, a subgroup analysis was performed of 33 e

30 Higher doses of echinocandins administered intermittently may be an alte

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

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

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

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

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

36 alysis of the efficacy of the dehydroxylated echinocandins against resistant Candida strains, which c

37 However, the efficacy of echinocandins against the pathogen Aspergillus fumigatus

38 All three echinocandin agents currently available have been shown

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

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

41 tifungal treatment, 1258 (68.6%) received an echinocandin and 543 (29.6%) received fluconazole as ini

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

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

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

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

46 We report the echinocandin and triazole antifungal susceptibility patt

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

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

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

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

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

52 The echinocandins and triazoles were active against Aspergil

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

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

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

56 o acid 3S,4S-dihydroxy-l-homotyrosine of the echinocandins anidulafungin and rezafungin, restored the

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

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

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

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

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

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

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

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

65 Anidulafungin is an echinocandin antifungal agent with potent activity again

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

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

68 The echinocandin antifungal caspofungin inhibits synthesis o

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

70 against C. albicans resistant to first-line echinocandin antifungals and potentiate non-curative ech

71 rn Asian lineage by exposure to triazole and echinocandin antifungals but not by exposure to amphoter

72 f reduced susceptibility to the triazole and echinocandin antifungals.

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

74 Echinocandins are a family of fungal lipidated cyclic he

75 Echinocandins are a group of antifungal agents that targ

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

77 The echinocandins are being used increasingly as therapy for

78 Echinocandins are frontline antifungals, but rising resi

79 The echinocandins are large lipopeptide molecules that are i

80 The echinocandins are large lipopeptide molecules that, sinc

81 Echinocandins are N-acyl-substituted cyclic hexapeptides

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

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

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

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

86 Echinocandins are recommended for Candia glabrata candid

87 The echinocandins are relatively new antifungal drugs that r

88 Echinocandins are the recommended treatment for invasive

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

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

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

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

93 ycete Glarea lozoyensis than to those of the echinocandin B gene cluster from A. pachycristatus.

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

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

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

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

98 ion therapy with a mold-active triazole plus echinocandin be administered versus mold-active triazole

99 ion therapy with a mold-active triazole plus echinocandin be administered vs. mold-active triazole mo

100 Phylogenetic analysis of the genes of the echinocandin biosynthetic family indicated that most of

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

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

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

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

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

106 Echinocandins (caspofungin, micafungin, and anidulafungi

107 By inhibiting beta-1,3-glucan synthesis, echinocandins cause both fungistatic stunting of hyphal

108 Echinocandin CBPs are insensitive for detecting emerging

109 The echinocandin class of antifungal agents is considered to

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

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

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

113 Echinocandins comprise a class of lipopeptide compounds

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

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

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

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

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

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

120 All echinocandins displayed limited activity against Cryptoc

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

122 Although echinocandins do not completely inhibit in vitro growth

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

124 The echinocandin drugs (micafungin, anidulafungin, and caspo

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

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

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

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

129 Echinocandins exert in vitro and in vivo fungicidal acti

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

131 Rezafungin (RZF) is a novel echinocandin exhibiting distinctive pharmacokinetics/pha

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

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

134 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 </=

135 During echinocandin exposure, the tps2Delta strain fails to com

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

137 ains at baseline and then were selected upon echinocandin exposure.

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

139 Echinocandin failure in C. glabrata is linked exclusivel

140 onclude that membrane sphingolipids modulate echinocandin-Fks interaction.

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

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

143 e cluster suggest a closer relationship with echinocandins from Leotiomycete fungi.

144 cated the divergent evolutionary lineages of echinocandin gene clusters are descendants from a common

145 nto a comprehensive phylogenetic analysis of echinocandin gene clusters indicated the divergent evolu

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

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

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

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

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

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

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

153 All three echinocandins have excellent in vitro activities against

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

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

156 ilable in 363 (94%) of the institutions, one echinocandin in 346 (89%), and liposomal amphotericin B

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

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

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

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

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

162 ce (ssNMR) and other techniques to show that echinocandins induce dynamic changes in the assembly of

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

164 Antifungal echinocandins inhibit the biosynthesis of beta-1,3-gluca

165 ates susceptibility of enzymatic activity to echinocandin inhibition.

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

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

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

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

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

171 The antifungal echinocandin lipopeptide, acrophiarin, was circumscribed

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

173 Echinocandins may be used for empiric therapy for C. gui

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

175 The new echinocandin micafungin has excellent in vitro activity

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

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

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

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

180 Treatment response and echinocandin minimum inhibitory concentrations varied am

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

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

183 A total of 51 episodes were treated with echinocandins (n=21), amphotericin-B-based therapy (n=22

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

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

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

187 de to administer a mold-active agent with an echinocandin or a mold-active azole when systemic antifu

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

189 therapy with a mold-active triazole plus an echinocandin or initial mold-active triazole monotherapy

190 n therapy was common (37.0%), mainly with an echinocandin or liposomal amphotericin B.

191 ved appropriate targeted therapy with either echinocandins or fluconazole were included.

192 ed treatment guidelines in 2016 to recommend echinocandins over fluconazole as first-line treatment f

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

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

195 tericin B can kill intracellular C. glabrata echinocandin persisters, reducing emergence of resistanc

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

197 The echinocandins prevent fungal cell wall synthesis by inhi

198 Penicillium arenicola and echinocandin-producing Aspergillus species belong to the

199 . arenicola bears similarity to Leotiomycete echinocandin-producing species because it exhibits self-

200 In total, 161 patients (58%) received echinocandin prophylaxis prior to azole initiation.

201 The echinocandins provide a new therapy for Candida esophagi

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

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

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

205 Clinical echinocandin resistance among Candida glabrata strains i

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

207 the link between ergosterol biosynthesis and echinocandin resistance and have implications for combin

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

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

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

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

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

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

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

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

216 Echinocandin resistance is increasing, including among F

217 so in Candida tropicalis infection; acquired echinocandin resistance remains uncommon.

218 ain-containing protein, CgSet4, in azole and echinocandin resistance via negative regulation of multi

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

220 mutations associated to azole resistance and echinocandin resistance were detected in Candida glabrat

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

222 troduction of the Fks1S639F allele increased echinocandin resistance, while correction of the Fks1S63

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

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

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

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

227 fungicidal activity with caspofungin against echinocandin resistant isolates.

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

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

230 e facilities worldwide, and the emergence of echinocandin-resistant C. auris is a concern.

231 g their effectiveness in the surveillance of echinocandin-resistant C. auris.

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

233 ored their efficacy against a large panel of echinocandin-resistant Candida strains.

234 f the Fks1S639F to the Fks1WT sequence in an echinocandin-resistant clade I isolate restored echinoca

235 All echinocandin-resistant isolates carried a mutation eithe

236 expanding the persister reservoir from which echinocandin-resistant mutants emerge.

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

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

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

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

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

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

243 inocandin-resistant clade I isolate restored echinocandin sensitivity.

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

245 tantly, all isolates remained susceptible to echinocandins, suggesting their efficacy as first-line t

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

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

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

249 ch encodes beta-1,6-glucan synthase, reduces echinocandin susceptibility in C. auris, further highlig

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

251 Echinocandin susceptibility was determined by Clinical a

252 r a synonymous mutation was introduced in an echinocandin-susceptible clade III isolate.

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

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

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

256 clinical blood culture who received empiric echinocandin therapy (+/-2 days of index Candida sp. blo

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

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

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

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

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

262 Initial echinocandin therapy was not associated with clinical fa

263 come in patients with IC receiving primarily echinocandin therapy.

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

265 Here, we uncover an endogenous mechanism of echinocandin tolerance in A. fumigatus whereby the induc

266 nical relevance of C. albicans diversity and echinocandin tolerance merits further investigation.

267 Findings suggest that echinocandin tolerant, euploid strains were a subpopulat

268 other concern is the multidrug-resistant and echinocandin-tolerant C parapsilosis isolates, which eme

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

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

271 no routine susceptibility testing with full echinocandin treatment course.

272 4; P </= .01) were independent predictors of echinocandin treatment failure.

273 Here we analyze the impact of echinocandin treatment of C. auris on beta-glucan exposu

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

275 ndin antifungals and potentiate non-curative echinocandin treatment.

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

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

278 da albicans, subinhibitory concentrations of echinocandins unmask immunostimulatory beta-glucan, augm

279 cytoskeletal organization, thereby enhancing echinocandin uptake and potency.

280 Echinocandin use prior to, but not concomitantly with, t

281 cantly associated with initial receipt of an echinocandin (versus fluconazole).

282 or children younger than 13 years of age, an echinocandin, voriconazole, or itraconazole is suggested

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

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

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

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

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

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

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

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

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

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

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

294 Echinocandins, which inhibit beta-glucan synthesis, are

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

296 recently developed antifungal drugs are the echinocandins, which noncompetitively inhibit beta-gluca

297 ant to the latest generation of antifungals, echinocandins, while Candida auris, a notorious global t

298 All FLZR-CP patients received targeted echinocandins, while FLZS-CP patients received either ec

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

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

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