ArticleAntimicrobial agents and chemotherapy2011
Paradoxical effect of caspofungin against Candida bloodstream isolates is mediated by multiple pathways but eliminated in human serum.
Article in Antimicrobial agents and chemotherapy, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
31 citing papers in PubMed, 1 synthesis or guideline pooled it, 64 citations in OpenAlex.
- Antifungal pharmacodynamics: Latin America's perspective.The Brazilian journal of infectious diseases : an official publication of the Brazilian Society of Infectious DiseasesPooled it
- Genomic and Molecular Identification of Genes Contributing to the Caspofungin Paradoxical Effect inMicrobiology spectrum · 2022Article
- Crosstalk between the calcineurin and cell wall integrity pathways prevents chitin overexpression in Candida albicans.Journal of cell science · 2021Article
- Relative Frequency of Paradoxical Growth and Trailing Effect with Caspofungin, Micafungin, Anidulafungin, and the Novel Echinocandin Rezafungin againstJournal of fungi (Basel, Switzerland) · 2020Article
- Review
- Aspergillus fumigatus and Aspergillosis in 2019.Clinical microbiology reviews · 2019Review
- Paradoxical growth effect of caspofungin on Candida spp. sessile cells not only at high drug concentrations.The Journal of antibiotics · 2019Article
- Treatment of Invasive Candidiasis: A Narrative Review.Journal of fungi (Basel, Switzerland) · 2018Review
- Dynamics of Mixed- Candida Species Biofilms in Response to Antifungals.Journal of dental research · 2018Article
- Review
- Recent Insights into the Paradoxical Effect of Echinocandins.Journal of fungi (Basel, Switzerland) · 2017Review
- Role of Virulence Determinants in Candida albicans' Resistance to Novel 2-bromo-2-chloro-2-(4-chlorophenylsulfonyl)-1-phenylethanone.Journal of fungi (Basel, Switzerland) · 2017Article
- ThemBio · 2017Article
- Frequency of the Paradoxical Effect Measured Using the EUCAST Procedure with Micafungin, Anidulafungin, and Caspofungin against Candida Species Isolates Causing Candidemia.Antimicrobial agents and chemotherapy · 2017Article
- Characterization of In Vitro Resistance Development to the Novel Echinocandin CD101 in Candida Species.Antimicrobial agents and chemotherapy · 2016Article
- Highly Dynamic and Specific Phosphatidylinositol 4,5-Bisphosphate, Septin, and Cell Wall Integrity Pathway Responses Correlate with Caspofungin Activity against Candida albicans.Antimicrobial agents and chemotherapy · 2016Article
- Antifungal Effect of Novel 2-Bromo-2-Chloro-2-(4-Chlorophenylsulfonyl)-1-Phenylethanone against Candida Strains.Frontiers in microbiology · 2016Article
- Antifungal pharmacokinetics and pharmacodynamics.Cold Spring Harbor perspectives in medicine · 2014Review
- Mechanisms of Antifungal Drug Resistance.Cold Spring Harbor perspectives in medicine · 2014Review
- Killing rates for caspofungin against Candida albicans after brief and continuous caspofungin exposure in the presence and absence of serum.Mycopathologia · 2014Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Paradoxical growth of Candida in vitro at echinocandin concentrations exceeding the MIC is well described, but the clinical relevance is unknown. We assessed echinocandin paradoxical effects against Candida bloodstream isolates (BSI) in the presence or absence of human serum and investigated regulatory mechanisms. As determined by broth microdilution, a paradoxical effect was evident for 60% (18/30), 23% (7/30), and 13% (4/30) of Candida albicans BSI exposed to caspofungin, anidulafungin, and micafungin, respectively, at achievable human serum concentrations (≤8 μg/ml). A paradoxical effect was not evident among 34 C. glabrata BSI and was observed only for caspofungin against C. parapsilosis (4%, 1/23). As determined in time-kill studies, a caspofungin paradoxical effect was demonstrated by C. albicans (2/3), C. glabrata (1/3), and C. parapsilosis (1/3), including BSI that were determined to be negative by microdilution. In 50% human serum, a paradoxical effect was eliminated at caspofungin concentrations up to 64 μg/ml for 100% (8/8) of the C. albicans BSI. A caspofungin paradoxical effect was also eliminated by chitin synthase inhibitor nikkomycin Z and at achievable concentrations of calcineurin pathway inhibitors, tacrolimus and cyclosporine. Moreover, these agents were synergistic with caspofungin against 100, 100, and 88% (7/8) of C. albicans, respectively, and exerted their own paradoxical effects. Finally, paradoxical growth was eliminated in C. albicans irs4- and inp51-null mutants, which lack phosphatidylinositol-(4,5)-bisphosphate 5'-phosphatase. Our findings suggest that the paradoxical effect is unlikely to be important in vivo but remains an important tool to study cell wall stress responses. We implicate the Irs4-Inp51 phosphatidylinositol-(4,5)-bisphosphate 5'-phosphatase as a novel regulator of paradoxical growth.
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Registered trials
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