Echinocandin Susceptibility Testing of Candida Isolates Collected during a 1-Year Period in Sweden

ABSTRACT The susceptibilities of Candida isolates to the echinocandins anidulafungin, caspofungin, and micafungin were determined by using the recently revised CLSI breakpoints and Etest on 238 clinical bloodstream Candida isolates collected between September 2005 and August 2006. The isolates represent approximately 95% of all non-albicans Candida bloodstream infections and one-third of Candida albicans bloodstream infections during this 1-year period in Sweden. The collection included 81 C. albicans, 81 C. glabrata, 36 C. parapsilosis, 14 C. dubliniensis, 8 C. tropicalis, 8 C. lusitaniae, 5 C. krusei, 2 C. guilliermondii and 2 C. inconspicua isolates as well as 1 C. pelliculosa isolate. The MICs were largely consistent with the global epidemiology of bloodstream Candida isolates. All C. albicans and C. glabrata isolates were susceptible to all 3 echinocandins (MIC ≤ 0.016 μg/ml in all instances). Resistance (MIC ≥ 8 μg/ml) to anidulafungin alone was observed for 4 (11.1%) C. parapsilosis isolates and for 1/2 C. guilliermondii isolates. Intermediate susceptibility to caspofungin alone was observed for 2/5 C. krusei isolates. One of the eight C. tropicalis isolates was classified as being intermediately susceptible to micafungin (MIC, 0.5 μg/ml) and as being resistant to anidulafungin and caspofungin (MIC ≥ 1 μg/ml). This isolate harbored a heterozygous FKS1 hot spot mutation (S80P) known to confer echinocandin resistance. This first study to apply the revised CLSI breakpoints for Etest endpoints showed that the breakpoints worked successfully in detecting an isolate with a hot spot mutation. Acquired echinocandin resistance is rare in Sweden. Echinocandin MICs against C. parapsilosis and C. guilliermondii were lowest for micafungin.

[1]  H. Schønheyder,et al.  National Surveillance of Fungemia in Denmark 2010-11 , 2012 .

[2]  Steven D. Brown,et al.  Clinical breakpoints for the echinocandins and Candida revisited: integration of molecular, clinical, and microbiological data to arrive at species-specific interpretive criteria. , 2011, Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy.

[3]  H. Schønheyder,et al.  National Surveillance of Fungemia in Denmark (2004 to 2009) , 2010, Journal of Clinical Microbiology.

[4]  J. Pemán,et al.  Comparison of Anidulafungin MICs Determined by the Clinical and Laboratory Standards Institute Broth Microdilution Method (M27-A3 Document) and Etest for Candida Species Isolates , 2009, Antimicrobial Agents and Chemotherapy.

[5]  J. Turnidge,et al.  Wild-Type MIC Distributions and Epidemiological Cutoff Values for the Echinocandins and Candida spp , 2009, Journal of Clinical Microbiology.

[6]  M. Arendrup,et al.  Echinocandin Susceptibility Testing of Candida Species: Comparison of EUCAST EDef 7.1, CLSI M27-A3, Etest, Disk Diffusion, and Agar Dilution Methods with RPMI and IsoSensitest Media , 2009, Antimicrobial Agents and Chemotherapy.

[7]  Russell E. Lewis,et al.  Candidemia in patients with hematologic malignancies in the era of new antifungal agents (2001‐2007) , 2009, Cancer.

[8]  M. Pfaller,et al.  In Vitro Activity of Seven Systemically Active Antifungal Agents against a Large Global Collection of Rare Candida Species as Determined by CLSI Broth Microdilution Methods , 2009, Journal of Clinical Microbiology.

[9]  E. Anaissie,et al.  Epidemiology and outcomes of candidemia in 2019 patients: data from the prospective antifungal therapy alliance registry. , 2009, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[10]  P. Annaert,et al.  Pharmacokinetics of caspofungin and voriconazole in critically ill patients during extracorporeal membrane oxygenation. , 2009, The Journal of antimicrobial chemotherapy.

[11]  M. Arendrup,et al.  Breakthrough Aspergillus fumigatus and Candida albicans Double Infection during Caspofungin Treatment: Laboratory Characteristics and Implication for Susceptibility Testing , 2008, Antimicrobial Agents and Chemotherapy.

[12]  D. Kontoyiannis,et al.  Caspofungin-Resistant Candida tropicalis Strains Causing Breakthrough Fungemia in Patients at High Risk for Hematologic Malignancies , 2008, Antimicrobial Agents and Chemotherapy.

[13]  M. Ghannoum,et al.  Correlation of MIC with Outcome for Candida Species Tested against Caspofungin, Anidulafungin, and Micafungin: Analysis and Proposal for Interpretive MIC Breakpoints , 2008, Journal of Clinical Microbiology.

[14]  S. Katiyar,et al.  A Naturally Occurring Proline-to-Alanine Amino Acid Change in Fks1p in Candida parapsilosis, Candida orthopsilosis, and Candida metapsilosis Accounts for Reduced Echinocandin Susceptibility , 2008, Antimicrobial Agents and Chemotherapy.

[15]  J. Versalovic,et al.  DNA pyrosequencing-based identification of pathogenic Candida species by using the internal transcribed spacer 2 region. , 2008, Archives of pathology & laboratory medicine.

[16]  G. Forrest,et al.  Increasing incidence of Candida parapsilosis candidemia with caspofungin usage. , 2008, The Journal of infection.

[17]  Subcommittee on Antifungal Susceptibility Testing EUCAST definitive document EDef 7.1: method for the determination of broth dilution MICs of antifungal agents for fermentative yeasts. , 2008, Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases.

[18]  H. Bonilla,et al.  Emergence of Candida tropicalis resistant to caspofungin. , 2007, The Journal of antimicrobial chemotherapy.

[19]  Clinical,et al.  Reference method for broth dilution antifungal susceptibility testing of yeasts : Approved standard , 2008 .

[20]  R. Betts,et al.  Micafungin versus caspofungin for treatment of candidemia and other forms of invasive candidiasis. , 2007, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[21]  M. Desnos-Ollivier,et al.  Acquired resistance to echinocandins in Candida albicans: case report and review. , 2007, The Journal of antimicrobial chemotherapy.

[22]  D. Pittet,et al.  Micafungin versus liposomal amphotericin B for candidaemia and invasive candidosis: a phase III randomised double-blind trial , 2007, The Lancet.

[23]  A. Brillowska-Dąbrowska,et al.  Five-Hour Diagnosis of Dermatophyte Nail Infections with Specific Detection of Trichophyton rubrum , 2007, Journal of Clinical Microbiology.

[24]  K. Anstrom,et al.  Comparative Evaluation of Etest and Sensititre YeastOne Panels against the Clinical and Laboratory Standards Institute M27-A2 Reference Broth Microdilution Method for Testing Candida Susceptibility to Seven Antifungal Agents , 2007, Journal of Clinical Microbiology.

[25]  C. Kibbler,et al.  Candida guilliermondii, an Opportunistic Fungal Pathogen with Decreased Susceptibility to Fluconazole: Geographic and Temporal Trends from the ARTEMIS DISK Antifungal Surveillance Program , 2006, Journal of Clinical Microbiology.

[26]  S. Katiyar,et al.  Candida albicans and Candida glabrata Clinical Isolates Exhibiting Reduced Echinocandin Susceptibility , 2006, Antimicrobial Agents and Chemotherapy.

[27]  L. Bevanger,et al.  Candidemia in Norway (1991 to 2003): Results from a Nationwide Study , 2006, Journal of Clinical Microbiology.

[28]  M. Cuenca‐Estrella,et al.  Epidemiology, Risk Factors, and Prognosis of Candida parapsilosis Bloodstream Infections: Case-Control Population-Based Surveillance Study of Patients in Barcelona, Spain, from 2002 to 2003 , 2006, Journal of Clinical Microbiology.

[29]  D. Perlin,et al.  Progressive loss of echinocandin activity following prolonged use for treatment of Candida albicans oesophagitis. , 2006, The Journal of antimicrobial chemotherapy.

[30]  D. Benjamin,et al.  Safety and Pharmacokinetics of Intravenous Anidulafungin in Children with Neutropenia at High Risk for Invasive Fungal Infections , 2006, Antimicrobial Agents and Chemotherapy.

[31]  N. Chao,et al.  Pharmacokinetic and Maximum Tolerated Dose Study of Micafungin in Combination with Fluconazole versus Fluconazole Alone for Prophylaxis of Fungal Infections in Adult Patients Undergoing a Bone Marrow or Peripheral Stem Cell Transplant , 2005, Antimicrobial Agents and Chemotherapy.

[32]  Lee H. Harrison,et al.  Incidence of Bloodstream Infections Due to Candida Species and In Vitro Susceptibilities of Isolates Collected from 1998 to 2000 in a Population-Based Active Surveillance Program , 2004, Journal of Clinical Microbiology.

[33]  J. Sobel,et al.  Guidelines for treatment of candidiasis. , 2004, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[34]  M. Arendrup,et al.  In Vivo Pathogenicity of Eight Medically Relevant Candida Species in an Animal Model , 2002, Infection.

[35]  J. Sobel,et al.  Practice guidelines for the treatment of candidiasis. Infectious Diseases Society of America. , 2000, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[36]  J. Sobel,et al.  Practice guidelines for the treatment of candidiasis. Infectious Diseases Society of America. , 2000, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[37]  J. Enders,et al.  Infectious Diseases Society of America. , 1969, Antimicrobial agents and chemotherapy.