Echinocandin Resistance in<i>Candida</i>Species: Mechanisms of Reduced Susceptibility and Therapeutic Approaches

Beyda, Nicholas D.; Lewis, Russell E.; Garey, Kevin W.

doi:10.1345/aph.1r020

Cited by 91 publications

(70 citation statements)

References 70 publications

(73 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The clinical impact of misidentifying C. albicans as C. dubliniensis is likely to be minimal, although it has been suggested that the development of fluconazole resistance is more likely for C. dubliniensis than for C. albicans (31). C. parapsilosis exhibits higher MICs for the echinocandins than do most other Candida species (8,32); therefore, misidentification might be clinically significant. However, data on the susceptibility profile of C. pelliculosa are sparse, and it is not obvious what empirical therapy might be initiated based on this identification.…”

Section: Discussionmentioning

confidence: 99%

Multicenter Study Evaluating the Vitek MS System for Identification of Medically Important Yeasts

et al. 2013

View full text Add to dashboard Cite

The optimal management of fungal infections is correlated with timely organism identification. Matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry (MS) is revolutionizing the identification of yeasts isolated from clinical specimens. We present a multicenter study assessing the performance of the Vitek MS system (bioMérieux) in identifying medically important yeasts. A collection of 852 isolates was tested, including 20 Candida species (626 isolates, including 58 C. albicans, 62 C. glabrata, and 53 C. krusei isolates), 35 Cryptococcus neoformans isolates, and 191 other clinically relevant yeast isolates; in total, 31 different species were evaluated. Isolates were directly applied to a target plate, followed by a formic acid overlay. Mass spectra were acquired using the Vitek MS system and were analyzed using the Vitek MS v2.0 database. The gold standard for identification was sequence analysis of the D2 region of the 26S rRNA gene. In total, 823 isolates (96.6%) were identified to the genus level and 819 isolates (96.1%) were identified to the species level. Twenty-four isolates (2.8%) were not identified, and five isolates (0.6%) were misidentified. Misidentified isolates included one isolate of C. albicans (n ‫؍‬ 58) identified as Candida dubliniensis, one isolate of Candida parapsilosis (n ‫؍‬ 73) identified as Candida pelliculosa, and three isolates of Geotrichum klebahnii (n ‫؍‬ 6) identified as Geotrichum candidum. The identification of clinically relevant yeasts using MS is superior to the phenotypic identification systems currently employed in clinical microbiology laboratories.

show abstract

Section: Discussionmentioning

confidence: 99%

Multicenter Study Evaluating the Vitek MS System for Identification of Medically Important Yeasts

et al. 2013

View full text Add to dashboard Cite

show abstract

“…However, the reason for the high MIC values for CAS is unclear (45) . Recent works have described a functional point mutation in the glucan synthase (FKS) gene of the C. parapsilosis complex species, which may explain this observation (46) (47) . FKS gene mutations have been shown to be associated with resistance to CAS, as demonstrated by increases in MICs in mutant isolates compared with those of wild-type isolates (48) (49) (50) .…”

Section: In Vitro Susceptibility Testingmentioning

confidence: 99%

Molecular identification and antifungal susceptibility profiles of Candida parapsilosis complex species isolated from culture collection of clinical samples

Ataídes

Costa

Souza

et al. 2015

Rev. Soc. Bras. Med. Trop.

View full text Add to dashboard Cite

Introduction:Candida parapsilosis is a common yeast species found in cases of onychomycosis and candidemia associated with infected intravascular devices. In this study, we differentiated Candida parapsilosis sensu stricto, Candida orthopsilosis, and Candida metapsilosis from a culture collection containing blood and subungual scraping samples. Furthermore, we assessed the in vitro antifungal susceptibility of these species to fl uconazole, itraconazole, voriconazole, posaconazole, amphotericin B, and caspofungin. Methods: Differentiation of C. parapsilosis complex species was performed by amplifi cation of the secondary alcohol dehydrogenase (SADH) gene and digestion by the restriction enzyme BanI. All isolates were evaluated for the determination of minimal inhibitory concentrations using Etest, a method for antifungal susceptibility testing. Results: Among the 87 isolates, 78 (89.7%) were identifi ed as C. parapsilosis sensu stricto, fi ve (5.7%) were identifi ed as C. orthopsilosis, and four (4.6%) were identifi ed as C. metapsilosis. Analysis of antifungal susceptibility showed that C. parapsilosis sensu stricto isolates were less susceptible to amphotericin B and itraconazole. One C. parapsilosis sensu stricto isolate was resistant to amphotericin B and itraconazole. Moreover, 10.2% of C. parapsilosis sensu stricto isolates were resistant to caspofungin. Two C. parapsilosis sensu stricto isolates and one C. metapsilosis isolate were susceptible to fl uconazole in a dose-dependent manner. Conclusions: We reported the fi rst molecular identifi cation of C. parapsilosis complex species in State of Goiás, Brazil. Additionally, we showed that although the three species exhibited differences in antifungal susceptibility profi les, the primary susceptibility of this species was to caspofungin.

show abstract

“…In contrast, pathogenic fungi resistant to azole and echinocandin antifungal drugs are now a serious concern. [1][2][3][4] These traits make AMB an ideal therapy for patients with unidentified invasive fungal infections.…”

Section: Introductionmentioning

confidence: 99%

NanoDisk containing super aggregated amphotericin B: a high therapeutic index antifungal formulation with enhanced potency

Burgess¹,

He²,

Baker³

et al. 2013

IJN

View full text Add to dashboard Cite

Objectives NanoDisk–amphotericin B (ND-AMB) is a protein-phospholipid bioparticle containing a “super aggregate” form of antifungal AMB. While lipid-based formulations of AMB, including liposomal AMB (L-AMB), are safer than the deoxycholate (DOC) solubilized form (DOC-AMB), the potency of lipid-based formulations is attenuated. We have developed an AMB-based therapy that is both well tolerated and fully efficacious. Methods Potency was determined using broth culture growth-inhibition assays and candidacidal kinetics by quantitative culture plating. Toxicology studies were performed in healthy mice. Efficacy was assessed using both immune-competent and leukopenic murine models of systemic Candida albicans infection. Results ND-AMB C. albicans and Aspergillus fumigatus minimum inhibitory concentrations were fourfold and sixfold lower, respectively, than that observed for L-AMB. ND-AMB exhibited candidacidal activity at 0.125 mg/L, 16-fold lower than L-AMB. In mice, ND-AMB produced no statistically significant kidney or liver toxicity at 15 mg/kg, the highest dose tested. When evaluated in immune-competent mice infected with C. albicans , ND-AMB was at least as effective as DOC-AMB or L-AMB. In a leukopenic model of candidiasis, the 50% effective dose of ND-AMB was around threefold lower than L-AMB. Conclusion These results indicate that ND-AMB exhibits a more favorable safety profile while maintaining uncompromised antifungal properties compared to both DOC-AMB and L-AMB. ND-AMB is a promising therapy for the treatment of invasive fungal infections.

show abstract

Echinocandin Resistance inCandidaSpecies: Mechanisms of Reduced Susceptibility and Therapeutic Approaches

Cited by 91 publications

References 70 publications

Multicenter Study Evaluating the Vitek MS System for Identification of Medically Important Yeasts

Multicenter Study Evaluating the Vitek MS System for Identification of Medically Important Yeasts

Molecular identification and antifungal susceptibility profiles of Candida parapsilosis complex species isolated from culture collection of clinical samples

NanoDisk containing super aggregated amphotericin B: a high therapeutic index antifungal formulation with enhanced potency

Contact Info

Product

Resources

About