Amy Elizabeth Delorme University of Alberta

Characterization of the Paradoxical Growth Effect of Candida Albicans Exposed to Caspofungin by Amy

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Characterization of the Paradoxical Growth Effect of Candida Albicans Exposed to Caspofungin

Author : Amy Elizabeth Delorme

Publisher : University of Alberta

Published : 2015

ISBN-10 :

ISBN-13 :

Number of Pages : 235 Pages

Language : en

Descriptions Characterization of the Paradoxical Growth Effect of Candida Albicans Exposed to Caspofungin

Candida albicans is an opportunistic pathogen and major cause of invasive fungal infections. Choice of antifungal therapy is complicated by the underlying associated diseases of patients infected, other drug interactions, and in vitro susceptibility of the isolate. Echinocandins are emerging as a preferred first line therapy in candidiasis, as they have few drug interactions or patient side effects, and have a fungal specific mode of action. However, in vitro susceptibility testing of caspofungin by broth microdilution has revealed an unexplained paradoxical growth (PG) effect in which there is noticeable growth at concentrations above the minimum inhibitory concentration (MIC) of susceptible isolates. This effect has not been fully characterized, but is believed to be a strictly in vitro phenomenon. The incidence of the PG effect varies between Candida strains, species, and growth forms and is affected my growth medium composition. My objectives were to more fully understand this effect by evaluating factors that affect in vitro growth with the echinocandin caspofungin (CASPO), including inoculum density and medium carbon source. I demonstrated that all C. albicans demonstrate the PG effect while C. glabrata, suggesting an intrinsic difference between species that demonstrate PG. Sequence and phylogenetic evaluation of the echinocandin target, glucan synthase, does not correlate with MIC or PG. Further in vitro evaluation by time kill analysis determined that medium carbon source modulates the PG effect. My research findings contribute to the growing body of evidence that suggests the action of echinocandins is not entirely concentration dependent and highlights the significant physiological differences between yeast grown at PG and inhibitory CASPO concentrations.

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Results Characterization of the Paradoxical Growth Effect of Candida Albicans Exposed to Caspofungin

Quadriphasic nature of the paradoxical growth effect observed in - [12][13][14] Second, a possible downside of high dosing of echinocandins is the Eagle effect or paradoxical growth effect, in which higher concentrations seem less effective than lower concentrations

Paradoxical Growth of Candida albicans in the Presence ... - ResearchGate - Many initial hypotheses to explain the paradoxical effect could be excluded: It has been demonstrated that paradoxical growth is not a result of resistance-associated mutations in the β-GS

Recent Insights into the Paradoxical Effect of Echinocandins - The occurrence of the paradoxical effect (PE) is a strain-and echinocandin-dependent trait, as five out of seven A. fumigatus clinical isolates presented paradoxical growth in the presence of

PDF Recent Insights into the Paradoxical Effect of Echinocandins - Another factor that was repeatedly reported to affect the occurrence of a paradoxical effect is sessile growth within a bioﬁlm as compared to conventional growth as planktonic cells [25,30,31]. Melo et al. analyzed the manifestation of the paradoxical effect for several isolates of C. albicans,

Paradoxical growth effect of caspofungin on - Nature - The Journal of Antibiotics - Paradoxical growth effect of caspofungin on Candida spp. sessile cells not only at high drug concentrations. ... characterization of less common bloodstream isolates

Deciphering Candida auris Paradoxical Growth Effect (Eagle Effect) in - The paradoxical growth effect (PGE; also known as Eagle effect) is an in vitro phenomenon observed during antifungal susceptibility testing (AFST). In PGE, some fungal isolates grow in medium containing high concentrations of an echinocandin, above the minimal inhibitory concentration (MIC), despite being fully susceptible at lower concentrations

(PDF) Paradoxical effect to caspofungin in Candida ... - ResearchGate - deﬁcient ﬂy model of cand ... C. parapsilosis , C. krusei ) were chosen for resistance characterization with CD101, anidulafungin and caspofungin. ... The Eagle effect is a paradoxical growth

PDF Identification of the Paradoxical Effect of Caspofungin ... - ResearchGate - Growth curves indicated the occurrence of the paradoxical effect varied between different echinocandins. Moreover, increased turbidity in the sensitivity test did not correlate with increased

The Eagle-Like Effect of the Echinocandins: Is It Relevant ... - Springer - The Eagle effect is a paradoxical growth phenomenon long known to exist in vitro with specific antimicrobial agents, particularly the penicillins. More recent reports have indicated that this effect also exists when Candida or Aspergillus species are exposed to the echinocandin antifungals. While the majority of data for this effect exists for caspofungin, there are also reports that

Paradoxical Effect of Echinocandins across Candida Species In Vitro - Paradoxical growth of some Candida isolates occurs at concentrations above the MIC for echinocandins. In 60 Candida bloodstream isolates from cancer patients (20 C. albicans isolates and 10 isolates each of C. parapsilosis, C. tropicalis, C. krusei, and

Changes in cell wall synthesis and ultrastructure during paradoxical - Paradoxical growth (PG) has been described for echinocandins and is characterized by cell growth at drug concentrations above the MIC. In this study, two isolates each of Candida albicans, C. tropicalis, C. orthopsilosis, and C. parapsilosis, all of which displaying PG in response to caspofungin, were subjected to MIC, minimal fungicidal concentration (MFC), and time-kill curve assays to

Paradoxical effect of caspofungin: reduced activity against Candida - Among a selected series of isolates tested at concentrations up to 50 microg/ml, an additional 53% showed a "mini-paradoxical effect": no turbid growth but incomplete killing at high concentrations (supra-minimum fungicidal concentration). These effects were reproducible; medium dependent in extent; noted in macro- and microdilution, in the

Evaluation of the possible influence of trailing and paradoxical - Paradoxical growth Trailing effect abstract Objective: Paradoxical growth (PG) and trailing effect (TE) are frequently observed during antifungal susceptibility testing (AFST). These two phenomena interfere with the determination of the minimal inhibitory concentration (MIC). The aim of this study was to assess the clinical impact of TE and PG

Recent Insights into the Paradoxical Effect of Echinocandins - MDPI - The paradoxical effect is characterized by the ability of certain fungal isolates to reconstitute growth in the presence of higher echinocandin concentrations, while being fully susceptible at lower concentrations. The nature of the paradoxical effect is not fully understood and has been the focus of multiple studies in the last two decades

Paradoxical growth effect of caspofungin observed on biofilms and - The paradoxical growth (PG) of Candida sp. biofilms in the presence of high caspofungin (CAS) concentrations was previously unknown. ... Paradoxical growth effect of caspofungin observed on biofilms and planktonic cells of five different Candida species Antimicrob Agents Chemother. 2007 Sep;51(9):3081-8. doi: 10.1128/AAC.00676-07

Paradoxical Growth Effect of Caspofungin Observed on Biofilms and - The paradoxical growth (PG) of Candida sp. biofilms in the presence of high caspofungin (CAS) concentrations was previously unknown. We sought to characterize the PG at supra-MICs of CAS among clinical Candida sp. isolates grown as biofilms in 96-well polystyrene microtiter plates. The MICs of CAS were determined for 30 clinical Candida sp. isolates (4 Candida albicans, 6 C. tropicalis, 7 C

Identification of the Paradoxical Effect of Caspofungin ... - ScienceDirect - Background: The paradoxical effect of fungi, (which is a special phenomenon that certain Candida spp. might exhibit augmented growth in the presence of echinocandin at some concentration higher than the minimum inhibitory concentration) would be better illustrated through growth ls and Methods: We investigated the paradoxical effect of caspofungin and micafungin on the growth and

Evaluation of the possible influence of trailing and paradoxical - Paradoxical growth (PG) and trailing effect (TE) are frequently observed during antifungal susceptibility testing (AFST). These two phenomena interfere with the determination of the minimal inhibitory concentration (MIC). The aim of this study was to assess the clinical impact of TE and PG

Studies of the paradoxical effect of caspofungin at high drug - 1.. IntroductionCaspofungin is an echinocandin inhibitor of fungal cell wall (1,3)-β-glucan synthesis (Deresinski and Stevens, 2003).It has recently been detailed (Stevens et al., 2004) that paradoxical turbid growth of Candida albicans isolates occurs in some high concentrations of caspofungin, above the minimum inhibitory was noted in 16% of isolates studied in broth

[PDF] Paradoxical Growth of Candida albicans in the Presence of - It is demonstrated that paradoxical growth of Candida albicans in the presence of caspofungin is not due to antifungal degradation or instability, and although this adaptation is associated with reduced virulence, the clinical implications remain to be elucidated. ABSTRACT In the last decade, echinocandins have emerged as an important family of antifungal drugs because of their fungicidal

Characterization of the Paradoxical | ERA - The incidence of the PG effect varies between Candida strains, species, and growth forms and is affected my growth medium composition. My objectives were to more fully understand this effect by evaluating factors that affect in vitro growth with the echinocandin caspofungin (CASPO), including inoculum density and medium carbon source

Identification of the paradoxical effect of caspofungin and micafungin - Background: The paradoxical effect of fungi, (which is a special phenomenon that certain Candida spp. might exhibit augmented growth in the presence of echinocandin at some concentration higher than the minimum inhibitory concentration) would be better illustrated through growth curves. Materials and methods: We investigated the paradoxical effect of caspofungin and micafungin on the growth

Download Characterization of the Paradoxical Growth Effect of Candida - Characterization of the Paradoxical Growth Effect of Candida Albicans Exposed to Caspofungin Summary Candida albicans is an opportunistic pathogen and major cause of invasive fungal infections. Choice of antifungal therapy is complicated by the underlying associated diseases of patients infected, other drug interactions, and in vitro

Paradoxical echinocandin activity: a limited in vitro phenomenon? - Quadriphasic nature of the paradoxical effect observed in vitro for caspofungin against (A) Candida albicans, and (B) Aspergillus 1, Subinhibitory phase; Phase 2, inhibition of growth at concentrations above the minimum inhibitory concentration/minimum effective concentration; Phase 3, attenuation of activity at highdrug concentrations; Phase 4, inhibition of growth at the

Paradoxical growth of Candida albicans in the presence of ... - PubMed - Paradoxical growth of Candida albicans in the presence of caspofungin is associated with multiple cell wall rearrangements and decreased virulence ... indicating that chitin is required but not sufficient to protect the cells from the fungicidal effect of caspofungin. Moreover, we found that after paradoxical growth, β-1,3-glucan was exposed

The Eagle-Like Effect of the Echinocandins: Is It Relevant - A paradoxical growth phenomenon with penicillin was first described by Harry Eagle and Musselman in 1948. In these studies, Eagle and Musselman described three “effective” concentrations of penicillin. The lowest is the concentration at which the rate of organism replication is reduced

Identification of the Paradoxical Effect of Caspofungin and - Background: The paradoxical effect of fungi, (which is a special phenomenon that certain Candida spp. might exhibit augmented growth in the presence of echinocandin at some concentration higher than the minimum inhibitory concentration) would be better illustrated through growth curves

Paradoxical growth effect of caspofungin observed on biofilms - What is the paradoxical growth of Candida sp biofilms at supra-MICs of CAS?

Deciphering Candida auris Paradoxical Growth Effect (Eagle - The paradoxical growth effect (PGE; also known as Eagle effect) is an in vitro phenomenon observed during antifungal susceptibility testing (AFST). In PGE, some fungal isolates grow in medium containing high concentrations of an echinocandin, above the minimal inhibitory concentration (MIC), despite being fully susceptible at lower concentrations

Paradoxical growth effect of caspofungin on Candida spp - Despite the growth-inhibitory activity of echinocandins at low drug concentrations, paradoxical growth (PG), defined as a re-growth at drug concentrations above the MIC, has been

Paradoxical growth effect of caspofungin on Candida spp - Paradoxical growth (PG) of Candida spp. planktonic cells promoted by echinocandins is widely reported. Here we report on the ability of Candida spp. sessile cells to display PG when they are exposed to caspofungin in vitro, even at relatively low drug concentrations. Clinical significance of PG during echinocandin therapy of candidiasis remains