Skip to main content
  • ASM
    • Antimicrobial Agents and Chemotherapy
    • Applied and Environmental Microbiology
    • Clinical Microbiology Reviews
    • Clinical and Vaccine Immunology
    • EcoSal Plus
    • Eukaryotic Cell
    • Infection and Immunity
    • Journal of Bacteriology
    • Journal of Clinical Microbiology
    • Journal of Microbiology & Biology Education
    • Journal of Virology
    • mBio
    • Microbiology and Molecular Biology Reviews
    • Microbiology Resource Announcements
    • Microbiology Spectrum
    • Molecular and Cellular Biology
    • mSphere
    • mSystems
  • Log in
  • My alerts
  • My Cart

Main menu

  • Home
  • Articles
    • Current Issue
    • Accepted Manuscripts
    • COVID-19 Special Collection
    • Archive
    • Minireviews
  • For Authors
    • Submit a Manuscript
    • Scope
    • Editorial Policy
    • Submission, Review, & Publication Processes
    • Organization and Format
    • Errata, Author Corrections, Retractions
    • Illustrations and Tables
    • Nomenclature
    • Abbreviations and Conventions
    • Publication Fees
    • Ethics Resources and Policies
  • About the Journal
    • About AAC
    • Editor in Chief
    • Editorial Board
    • For Reviewers
    • For the Media
    • For Librarians
    • For Advertisers
    • Alerts
    • AAC Podcast
    • RSS
    • FAQ
  • Subscribe
    • Members
    • Institutions
  • ASM
    • Antimicrobial Agents and Chemotherapy
    • Applied and Environmental Microbiology
    • Clinical Microbiology Reviews
    • Clinical and Vaccine Immunology
    • EcoSal Plus
    • Eukaryotic Cell
    • Infection and Immunity
    • Journal of Bacteriology
    • Journal of Clinical Microbiology
    • Journal of Microbiology & Biology Education
    • Journal of Virology
    • mBio
    • Microbiology and Molecular Biology Reviews
    • Microbiology Resource Announcements
    • Microbiology Spectrum
    • Molecular and Cellular Biology
    • mSphere
    • mSystems

User menu

  • Log in
  • My alerts
  • My Cart

Search

  • Advanced search
Antimicrobial Agents and Chemotherapy
publisher-logosite-logo

Advanced Search

  • Home
  • Articles
    • Current Issue
    • Accepted Manuscripts
    • COVID-19 Special Collection
    • Archive
    • Minireviews
  • For Authors
    • Submit a Manuscript
    • Scope
    • Editorial Policy
    • Submission, Review, & Publication Processes
    • Organization and Format
    • Errata, Author Corrections, Retractions
    • Illustrations and Tables
    • Nomenclature
    • Abbreviations and Conventions
    • Publication Fees
    • Ethics Resources and Policies
  • About the Journal
    • About AAC
    • Editor in Chief
    • Editorial Board
    • For Reviewers
    • For the Media
    • For Librarians
    • For Advertisers
    • Alerts
    • AAC Podcast
    • RSS
    • FAQ
  • Subscribe
    • Members
    • Institutions
Susceptibility

Frequency of the Paradoxical Effect Measured Using the EUCAST Procedure with Micafungin, Anidulafungin, and Caspofungin against Candida Species Isolates Causing Candidemia

Laura Judith Marcos-Zambrano, Pilar Escribano, Carlos Sánchez-Carrillo, Emilio Bouza, Jesús Guinea
Laura Judith Marcos-Zambrano
aClinical Microbiology and Infectious Diseases, Hospital General Universitario Gregorio Marañón, Madrid, Spain
bInstituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Pilar Escribano
aClinical Microbiology and Infectious Diseases, Hospital General Universitario Gregorio Marañón, Madrid, Spain
bInstituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Carlos Sánchez-Carrillo
aClinical Microbiology and Infectious Diseases, Hospital General Universitario Gregorio Marañón, Madrid, Spain
bInstituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain
cCIBER Enfermedades Respiratorias-CIBERES (CB06/06/0058), Madrid, Spain
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Emilio Bouza
aClinical Microbiology and Infectious Diseases, Hospital General Universitario Gregorio Marañón, Madrid, Spain
bInstituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain
cCIBER Enfermedades Respiratorias-CIBERES (CB06/06/0058), Madrid, Spain
dMedicine Department, School of Medicine, Universidad Complutense de Madrid, Madrid, Spain
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jesús Guinea
aClinical Microbiology and Infectious Diseases, Hospital General Universitario Gregorio Marañón, Madrid, Spain
bInstituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain
cCIBER Enfermedades Respiratorias-CIBERES (CB06/06/0058), Madrid, Spain
dMedicine Department, School of Medicine, Universidad Complutense de Madrid, Madrid, Spain
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Jesús Guinea
DOI: 10.1128/AAC.01584-16
  • Article
  • Figures & Data
  • Info & Metrics
  • PDF
Loading

ABSTRACT

We report data on the frequency of the paradoxical effect of echinocandins against Candida spp. (n = 602 incident isolates) using the EUCAST definitive document EDef 7.2 procedure. The paradoxical effect for one or more echinocandins was observed in 16% of the isolates. However, differences between species were found, and the paradoxical effect was more common in Candida tropicalis (P < 0.001). Caspofungin was the drug in which the paradoxical effect was most common, followed by anidulafungin and micafungin (P < 0.001).

TEXT

Treatment with echinocandins, i.e., caspofungin, micafungin, and anidulafungin, is recommended as the primary therapy for patients with candidemia (1, 2). Rates of resistance are low (3), but attenuation of activity at high concentrations, known as the paradoxical or Eagle effect, has been reported (4–7). Isolates are characterized by abnormal morphology when studied in the presence of high concentrations of echinocandins (8–10). Although it has been reported for all three echinocandins, differences in frequency by species have been pointed out, mostly by use of CLSI methodology (4, 11, 12). Antifungal lock therapy may prevent catheter removal in patients with candidemia. Since the procedure requires the catheter lumen to be filled with a solution containing a high concentration of echinocandins (13), the paradoxical effect may have a negative impact (14, 15).

(This study was presented in part at the 26th European Congress of Clinical Microbiology and Infectious Diseases [ECCMID], Amsterdam, Netherlands, 9 to 12 April 2016 [electronic poster EP0008].)

We studied the frequency of the paradoxical effect of echinocandins against 602 echinocandin-susceptible Candida species incident isolates from the blood cultures of patients with candidemia who were admitted to Gregorio Marañón Hospital from January 2007 to March 2015. All the strains were molecularly identified (Table 1) (16), and antifungal susceptibility to micafungin (Astellas Pharma, Inc., Tokyo, Japan), anidulafungin (Pfizer Pharmaceutical Group, New York, NY), and caspofungin (Merck &Co., Inc., Rahway, New Jersey, NJ) was determined using the EUCAST definitive document EDef 7.2 procedure (17). The candin concentrations tested ranged from 0.015 to 8 μg/ml. Candida krusei ATCC 6258 and Candida parapsilosis ATCC 22019 isolates were used as quality control strains. The paradoxical effect was defined as an increase in optical density of 0.02 compared with the growth control in wells containing a candin concentration at least 2 drug dilutions higher than the MIC (Fig. 1). This definition was adapted from a previous study (9). We calculated the frequency of the paradoxical effect at each concentration tested, overall and by species, and the percentage of isolates in which the paradoxical effect was observed (Kruskal-Wallis test). This study was approved by the Ethics Committee of Hospital Gregorio Marañón (CEIC-A1; study no. 252/15).

View this table:
  • View inline
  • View popup
TABLE 1

Species distribution and percentage of isolates, overall and by species, in which the paradoxical effect of caspofungin, anidulafungin, micafungin, or any combination of the three was observed at any drug concentration

FIG 1
  • Open in new tab
  • Download powerpoint
FIG 1

Example of an isolate showing paradoxical effect (PE) of caspofungin at MICs of 4 and 8 μg/ml. OD, optical density.

We used the EUCAST procedure and found a paradoxical effect for one or more echinocandins in 16% (n = 96) of the isolates; it was most frequent in caspofungin, followed by anidulafungin and micafungin (Fig. 2) (P < 0.001), as reported previously in studies using the method in CLSI document M27-A3 (4, 10, 18). Caspofungin had a paradoxical effect against Candida tropicalis, C. parapsilosis, and other Candida spp., whereas anidulafungin presented the effect more frequently than caspofungin and micafungin against Candida albicans and Candida glabrata. Micafungin was the agent for which the effect was least frequent. Overall, the three echinocandins are similar in terms of pharmacological properties and spectra of activity; however, micafungin tends to show lower MICs against C. glabrata. Furthermore, our observations support previous findings that micafungin causes the paradoxical effect in a lower proportion of C. glabrata isolates (11, 19).

FIG 2
  • Open in new tab
  • Download powerpoint
FIG 2

Percentage of isolates, overall and per species, in which the paradoxical effect of caspofungin, anidulafungin, micafungin, or any combination of the three was observed.

We found the effect to be species specific; C. tropicalis had the highest proportion of strains (64%) in which one or more echinocandins produced a paradoxical effect, followed by C. albicans (14.8%) (Fig. 2). The high percentage of C. tropicalis isolates showing paradoxical effect was previously reported (18). The high percentage of other Candida species isolates in which the effect was observed has been mainly attributed to Candida dubliniensis (4/5) and Candida guilliermondii (4/8) (11).

Chamilos et al. (18) showed that the paradoxical effect of caspofungin was found in a high proportion (90%) of C. parapsilosis isolates when using the CLSI method; however, we only detected the effect in 6.7% of C. parapsilosis isolates with the EUCAST procedure. This discrepancy may be due to differences between the EUCAST and CLSI methods, the low number of isolates analyzed by Chamilos et al., or the chosen definitions of the paradoxical effect.

The paradoxical effect was observed at low concentrations of ≥0.125 μg/ml (anidulafungin) and ≥0.25 μg/ml (caspofungin and micafungin); previous studies using the CLSI method reported the presence of the paradoxical effect at high concentrations (2 to 64 μg/ml) (4, 11, 18). Use of the EUCAST procedure would probably explain the presence of the effect at lower concentrations; however, we found that the higher the echinocandin concentration, the higher the proportion of isolates in which the effect was observed (Table 1). Furthermore, the phenomenon was not only concentration dependent but also drug dependent, as shown by the fact that caspofungin and anidulafungin caused the paradoxical effect in a higher percentage of isolates than caused by micafungin, to the extent that the drug concentration rose (P < 0.05) (Table 1). However, in vitro antifungal activity of caspofungin obtained by the EUCAST or CLSI procedure should be interpreted carefully because of the interlaboratory variations reported when using this drug (20). This observation was not reported with use of the colorimetric marketed system YeastOne assay (21).

The concentrations at which the paradoxical effect was observed in vitro were easily reached in plasma (5); the addition of serum to the trays reversed the effect (10), probably as a consequence of albumin binding, suggesting that the paradoxical effect may only have a clinical impact on anatomical sites at which the free fraction of echinocandins reached is high. Few data support the clinical impact of the paradoxical effect, and high-dose echinocandin regimens have been shown to be as effective as regular dose regimens (14, 15). Antifungal lock therapy requires concentrations that are at least 1,000-fold greater than the MIC over a prolonged period in order to provide a suitable environment for the paradoxical effect (13). Future studies should evaluate the clinical impact of promoting the paradoxical effect when using echinocandins in lock therapy (5, 7).

The mechanism of action of the paradoxical effect is not fully understood, but it probably involves the integrity of the cell wall (5, 7, 10). Since these changes enable the cell to adapt to an environment with high echinocandin concentrations, the paradoxical effect is more a mechanism of tolerance than of resistance, albeit with a cost in fitness and virulence (9).

We only tested echinocandin concentrations of up to 8 μg/ml. Previous studies using the CLSI method showed the presence of the paradoxical effect at concentrations ranging from 2 to 64 μg/ml (4, 8, 11, 18). However, a key strength of our study is the detection of the paradoxical effect coupled with the MIC reading. This finding may prove particularly relevant if the phenomenon is shown to have a clinical impact.

We conclude that the paradoxical effect is easily detected using the EUCAST procedure, and it is seen mainly with caspofungin and in C. tropicalis.

ACKNOWLEDGMENTS

We thank Thomas O'Boyle for editing the article.

We have no conflicts of interest to report.

This study was supported by grant ref. CM-SANTANDER (GR3/2014; group 920200), grant no. PI14/00740 from Fondo de Investigación Sanitaria (FIS; Instituto de Salud Carlos III, Madrid, Spain; Plan Nacional de I+D+I 2013-2016), and the European Regional Development Fund (FEDER; “A way of making Europe”).

The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.

P.E. (CPI15/00115), J.G. (CPII15/00006), and L.J.M.-Z. (FI12/00265) are supported by FIS.

FOOTNOTES

    • Received 20 July 2016.
    • Returned for modification 20 September 2016.
    • Accepted 24 October 2016.
    • Accepted manuscript posted online 31 October 2016.
  • Copyright © 2016 American Society for Microbiology.

All Rights Reserved .

REFERENCES

  1. 1.↵
    1. Pappas PG,
    2. Kauffman CA,
    3. Andes DR,
    4. Clancy CJ,
    5. Marr KA,
    6. Ostrosky-Zeichner L,
    7. Reboli AC,
    8. Schuster MG,
    9. Vazquez JA,
    10. Walsh TJ,
    11. Zaoutis TE,
    12. Sobel JD
    . 2016. Clinical practice guideline for the management of candidiasis: 2016 update by the Infectious Diseases Society of America. Clin Infect Dis62:1–4. doi:10.1093/cid/civ93.
    OpenUrlCrossRefPubMed
  2. 2.↵
    1. Perlin DS
    . 2015. Echinocandin resistance in Candida. Clin Infect Dis61(Suppl 6):S612–S617. doi:10.1093/cid/civ791.
    OpenUrlCrossRefPubMed
  3. 3.↵
    1. Arendrup MC,
    2. Perlin DS
    . 2014. Echinocandin resistance: an emerging clinical problem?Curr Opin Infect Dis27:484–492. doi:10.1097/QCO.0000000000000111.
    OpenUrlCrossRefPubMed
  4. 4.↵
    1. Stevens DA,
    2. Espiritu M,
    3. Parmar R
    . 2004. Paradoxical effect of caspofungin: reduced activity against Candida albicans at high drug concentrations. Antimicrob Agents Chemother48:3407–3411. doi:10.1128/AAC.48.9.3407-3411.2004.
    OpenUrlAbstract/FREE Full Text
  5. 5.↵
    1. Vanstraelen K,
    2. Lagrou K,
    3. Maertens J,
    4. Wauters J,
    5. Willems L,
    6. Spriet I
    . 2013. The Eagle-like effect of echinocandins: what's in a name?Expert Rev Anti Infect Ther11:1179–1191. doi:10.1586/14787210.2013.841543.
    OpenUrlCrossRefPubMed
  6. 6.↵
    1. Stevens DA
    . 2009. Frequency of paradoxical effect with caspofungin in Candida albicans. Eur J Clin Microbiol Infect Dis28:717. doi:10.1007/s10096-008-0688-y.
    OpenUrlCrossRefPubMed
  7. 7.↵
    1. Steinbach WJ,
    2. Lamoth F,
    3. Juvvadi PR
    . 2015. Potential microbiological effects of higher dosing of echinocandins. Clin Infect Dis61(Suppl 6):S669–S677. doi:10.1093/cid/civ725.
    OpenUrlCrossRefPubMed
  8. 8.↵
    1. Bizerra FC,
    2. Melo AS,
    3. Katchburian E,
    4. Freymuller E,
    5. Straus AH,
    6. Takahashi HK,
    7. Colombo AL
    . 2011. Changes in cell wall synthesis and ultrastructure during paradoxical growth effect of caspofungin on four different Candida species. Antimicrob Agents Chemother55:302–310. doi:10.1128/AAC.00633-10.
    OpenUrlAbstract/FREE Full Text
  9. 9.↵
    1. Rueda C,
    2. Cuenca-Estrella M,
    3. Zaragoza O
    . 2014. Paradoxical growth of Candida albicans in the presence of caspofungin is associated with multiple cell wall rearrangements and decreased virulence. Antimicrob Agents Chemother58:1071–1083. doi:10.1128/AAC.00946-13.
    OpenUrlAbstract/FREE Full Text
  10. 10.↵
    1. Shields RK,
    2. Nguyen MH,
    3. Du C,
    4. Press E,
    5. Cheng S,
    6. Clancy CJ
    . 2011. Paradoxical effect of caspofungin against Candida bloodstream isolates is mediated by multiple pathways but eliminated in human serum. Antimicrob Agents Chemother55:2641–2647. doi:10.1128/AAC.00999-10.
    OpenUrlAbstract/FREE Full Text
  11. 11.↵
    1. Fleischhacker M,
    2. Radecke C,
    3. Schulz B,
    4. Ruhnke M
    . 2008. Paradoxical growth effects of the echinocandins caspofungin and micafungin, but not of anidulafungin, on clinical isolates of Candida albicans and C. dubliniensis. Eur J Clin Microbiol Infect Dis27:127–131. doi:10.1007/s10096-007-0411-4.
    OpenUrlCrossRefPubMedWeb of Science
  12. 12.↵
    1. Miceli MH,
    2. Bernardo SM,
    3. Lee SA
    . 2009. In vitro analysis of the occurrence of a paradoxical effect with different echinocandins and Candida albicans biofilms. Int J Antimicrob Agents34:500–502. doi:10.1016/j.ijantimicag.2009.07.001.
    OpenUrlCrossRefPubMed
  13. 13.↵
    1. Walraven CJ,
    2. Lee SA
    . 2013. Antifungal lock therapy. Antimicrob Agents Chemother57:1–8. doi:10.1128/AAC.01351-12.
    OpenUrlAbstract/FREE Full Text
  14. 14.↵
    1. Betts RF,
    2. Nucci M,
    3. Talwar D,
    4. Gareca M,
    5. Queiroz-Telles F,
    6. Bedimo RJ,
    7. Herbrecht R,
    8. Ruiz-Palacios G,
    9. Young JA,
    10. Baddley JW,
    11. Strohmaier KM,
    12. Tucker KA,
    13. Taylor AF,
    14. Kartsonis NA
    . 2009. A multicenter, double-blind trial of a high-dose caspofungin treatment regimen versus a standard caspofungin treatment regimen for adult patients with invasive candidiasis. Clin Infect Dis48:1676–1684. doi:10.1086/598933.
    OpenUrlCrossRefPubMedWeb of Science
  15. 15.↵
    1. Safdar A,
    2. Rodriguez G,
    3. Rolston KV,
    4. O'Brien S,
    5. Khouri IF,
    6. Shpall EJ,
    7. Keating MJ,
    8. Kantarjian HM,
    9. Champlin RE,
    10. Raad II,
    11. Kontoyiannis DP
    . 2007. High-dose caspofungin combination antifungal therapy in patients with hematologic malignancies and hematopoietic stem cell transplantation. Bone Marrow Transplant39:157–164. doi:10.1038/sj.bmt.1705559.
    OpenUrlCrossRefPubMedWeb of Science
  16. 16.↵
    1. White T,
    2. Bruns T,
    3. Lee S,
    4. Taylor J
    . 1990. Amplification and direct sequencing of fungal ribosomal RNA genes for phylogenetics, p 322. InMichael A, Innis DHG, Sninsky JJ, White TJ (ed), PCR protocols: a guide to methods and applications. Academic Press,San Diego, CA.
  17. 17.↵
    1. Arendrup MC,
    2. Cuenca-Estrella M,
    3. Lass-Florl C,
    4. Hope W
    . 2012. EUCAST technical note on the EUCAST definitive document EDef 7.2: method for the determination of broth dilution minimum inhibitory concentrations of antifungal agents for yeasts EDef 7.2 (EUCAST-AFST). Clin Microbiol Infect18:E246–E247. doi:10.1111/j.1469-0691.2012.03880.x.
    OpenUrlCrossRefPubMed
  18. 18.↵
    1. Chamilos G,
    2. Lewis RE,
    3. Albert N,
    4. Kontoyiannis DP
    . 2007. Paradoxical effect of echinocandins across Candida species in vitro: evidence for echinocandin-specific and Candida species-related differences. Antimicrob Agents Chemother51:2257–2259. doi:10.1128/AAC.00095-07.
    OpenUrlAbstract/FREE Full Text
  19. 19.↵
    1. Arendrup MC,
    2. Perlin DS,
    3. Jensen RH,
    4. Howard SJ,
    5. Goodwin J,
    6. Hope W
    . 2012. Differential in vivo activities of anidulafungin, caspofungin, and micafungin against Candida glabrata isolates with and without FKS resistance mutations. Antimicrob Agents Chemother56:2435–2442. doi:10.1128/AAC.06369-11.
    OpenUrlAbstract/FREE Full Text
  20. 20.↵
    1. Espinel-Ingroff A,
    2. Arendrup MC,
    3. Pfaller MA,
    4. Bonfietti LX,
    5. Bustamante B,
    6. Canton E,
    7. Chryssanthou E,
    8. Cuenca-Estrella M,
    9. Dannaoui E,
    10. Fothergill A,
    11. Fuller J,
    12. Gaustad P,
    13. Gonzalez GM,
    14. Guarro J,
    15. Lass-Florl C,
    16. Lockhart SR,
    17. Meis JF,
    18. Moore CB,
    19. Ostrosky-Zeichner L,
    20. Pelaez T,
    21. Pukinskas SR,
    22. St-Germain G,
    23. Szeszs MW,
    24. Turnidge J
    . 2013. Interlaboratory variability of caspofungin MICs for Candida spp. using CLSI and EUCAST methods: should the clinical laboratory be testing this agent?Antimicrob Agents Chemother57:5836–5842. doi:10.1128/AAC.01519-13.
    OpenUrlAbstract/FREE Full Text
  21. 21.↵
    1. Eschenauer GA,
    2. Nguyen MH,
    3. Shoham S,
    4. Vazquez JA,
    5. Morris AJ,
    6. Pasculle WA,
    7. Kubin CJ,
    8. Klinker KP,
    9. Carver PL,
    10. Hanson KE,
    11. Chen S,
    12. Lam SW,
    13. Potoski BA,
    14. Clarke LG,
    15. Shields RK,
    16. Clancy CJ
    . 2014. Real-world experience with echinocandin MICs against Candida species in a multicenter study of hospitals that routinely perform susceptibility testing of bloodstream isolates. Antimicrob Agents Chemother58:1897–1906. doi:10.1128/AAC.02163-13.
    OpenUrlAbstract/FREE Full Text
View Abstract
PreviousNext
Back to top
Download PDF
Citation Tools
Frequency of the Paradoxical Effect Measured Using the EUCAST Procedure with Micafungin, Anidulafungin, and Caspofungin against Candida Species Isolates Causing Candidemia
Laura Judith Marcos-Zambrano, Pilar Escribano, Carlos Sánchez-Carrillo, Emilio Bouza, Jesús Guinea
Antimicrobial Agents and Chemotherapy Dec 2016, 61 (1) e01584-16; DOI: 10.1128/AAC.01584-16

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Print

Alerts
Sign In to Email Alerts with your Email Address
Email

Thank you for sharing this Antimicrobial Agents and Chemotherapy article.

NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. We do not retain these email addresses.

Enter multiple addresses on separate lines or separate them with commas.
Frequency of the Paradoxical Effect Measured Using the EUCAST Procedure with Micafungin, Anidulafungin, and Caspofungin against Candida Species Isolates Causing Candidemia
(Your Name) has forwarded a page to you from Antimicrobial Agents and Chemotherapy
(Your Name) thought you would be interested in this article in Antimicrobial Agents and Chemotherapy.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
Frequency of the Paradoxical Effect Measured Using the EUCAST Procedure with Micafungin, Anidulafungin, and Caspofungin against Candida Species Isolates Causing Candidemia
Laura Judith Marcos-Zambrano, Pilar Escribano, Carlos Sánchez-Carrillo, Emilio Bouza, Jesús Guinea
Antimicrobial Agents and Chemotherapy Dec 2016, 61 (1) e01584-16; DOI: 10.1128/AAC.01584-16
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Top
  • Article
    • ABSTRACT
    • TEXT
    • ACKNOWLEDGMENTS
    • FOOTNOTES
    • REFERENCES
  • Figures & Data
  • Info & Metrics
  • PDF

KEYWORDS

antifungal agents
Candida
echinocandins
lipopeptides
paradoxical effect
echinocandins
Candida
EUCAST

Related Articles

Cited By...

About

  • About AAC
  • Editor in Chief
  • Editorial Board
  • Policies
  • For Reviewers
  • For the Media
  • For Librarians
  • For Advertisers
  • Alerts
  • AAC Podcast
  • RSS
  • FAQ
  • Permissions
  • Journal Announcements

Authors

  • ASM Author Center
  • Submit a Manuscript
  • Article Types
  • Ethics
  • Contact Us

Follow #AACJournal

@ASMicrobiology

       

ASM Journals

ASM journals are the most prominent publications in the field, delivering up-to-date and authoritative coverage of both basic and clinical microbiology.

About ASM | Contact Us | Press Room

 

ASM is a member of

Scientific Society Publisher Alliance

 

American Society for Microbiology
1752 N St. NW
Washington, DC 20036
Phone: (202) 737-3600

Copyright © 2021 American Society for Microbiology | Privacy Policy | Website feedback

Print ISSN: 0066-4804; Online ISSN: 1098-6596