title: Susceptibility to echinocandins of Candida spp. strains isolated in Italy assessed by European Committee for Antimicrobial Susceptibility Testing and Clinical Laboratory Standards Institute broth microdilution methods.
abstract: BACKGROUND
  The echinocandins are recommended as first-line therapy for Candida species infections, but drug resistance, especially among Candida glabrata, is becoming more frequent. We investigated the antifungal susceptibility of anidulafungin, caspofungin, and micafungin against 584 isolates of Candida spp. (bloodstream, other sterile sites) collected from patients admitted to an Italian university hospital between 2000 and 2013. The susceptibility was evaluated using the broth microdilution method according to both the European Committee for Antimicrobial Susceptibility Testing (EUCAST EDef 7.2) and the Clinical Laboratory Standards Institute (CLSI M27-A3). The echinocandin susceptibilities were assessed on the basis of the species-specific clinical breakpoints proposed by the EUCAST version 6.1 and CLSI M27-S4 documents. The two methods were comparable by assessing essential agreement (EA), categorical agreement (CA), and Spearman's correlation analysis (rho, r).
  
  
  RESULTS
  The modal minimum inhibitory concentrations (MICs; μg ⋅ mL (-1)) values by both methods (EUCAST/CLSI) for anidulafungin, caspofungin, and micafungin for each species were, respectively, as follows: C. albicans, 0.03/0.12, 0.016/0.5, and 0.016/0.008; C. parapsilosis complex, 2/1, 2/2, and 2/1; C. tropicalis, 0.06/0.12, 0.06/0.12, and 0.06/0.12; C. glabrata complex, 0.03/0.25, 0.06/0.12, and 0.03/0.06; C. guilliermondii, 2/1, 2/2, and 2/2; and C. krusei, 0.06/0.12, 0.12/0.5, and 0.06/0.12. The overall resistance rates for EUCAST/CLSI were as follows: anidulafungin, 2.5/0.9%; caspofungin, breakpoint not available/3.8%; micafungin, 2.7/1.5%. Candida glabrata complex was the least susceptible to all three echinocandins, and the percentages of resistant isolates by EUCAST/CLSI were as follows: anidulafungin, 13.5/2.7%; caspofungin, breakpoint not available/16.2%; micafungin, 18.9/13.5%. The overall EA was 93 % for micafungin, 92% for anidulafungin, and 90% for caspofungin. The CA was >90% for all organism-drug combinations with the exception of C. glabrata and anidulafungin (89%). Spearman's rho for EUCAST/CLSI was 0.89 (p < 0.001) for caspofungin, 0.85 (p < 0.001) for anidulafungin, and 0.83 for micafungin (p < 0.001).
  
  
  CONCLUSIONS
  Independent of the procedure applied, no alarming resistance to the tested agents was found, although a reduced susceptibility was detected for C. glabrata complex. The EUCAST and CLSI methods produce similar MICs, indicating that using one method or the other should not result in susceptibilities different enough to affect treatment decisions.
authors.affiliation: Department of Biomedical Science and Human Oncology, Hygiene Section, University of Bari "Aldo Moro", Piazza Giulio Cesare 11, Bari, Italy. mariateresa.montagna@uniba.it.
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Montagna
authors.affiliation: Department of Biomedical Science and Human Oncology, Hygiene Section, University of Bari "Aldo Moro", Piazza Giulio Cesare 11, Bari, Italy. raz.ro@tiscali.it.
authors.forename: Grazia
authors.initials: G
authors.lastname: Lovero
authors.affiliation: Department of Biomedical Science and Human Oncology, Hygiene Section, University of Bari "Aldo Moro", Piazza Giulio Cesare 11, Bari, Italy. catiacoretti@yahoo.it.
authors.forename: Caterina
authors.initials: C
authors.lastname: Coretti
authors.affiliation: Department of Medical and Surgical Sciences, Hygiene Section, University of Foggia, Via Gramsci 89-91, 71100, Foggia, Italy. domenico.martinelli@unifg.it.
authors.forename: Domenico
authors.initials: D
authors.lastname: Martinelli
authors.affiliation: Department of Biomedical Science and Human Oncology, Hygiene Section, University of Bari "Aldo Moro", Piazza Giulio Cesare 11, Bari, Italy. osvalda.degiglio@uniba.it.
authors.forename: Osvalda
authors.initials: O
authors.lastname: De Giglio
authors.affiliation: Department of Veterinary Medicine, University of Bari Aldo Moro, Str. Prov. per Casamassima Km 3, Valenzano, Bari, Italy. iroberta@hotmail.com.
authors.forename: Roberta
authors.initials: R
authors.lastname: Iatta
authors.affiliation: Department of Biomedical Science and Human Oncology, Hygiene Section, University of Bari "Aldo Moro", Piazza Giulio Cesare 11, Bari, Italy. stella.balbino@gmail.com.
authors.forename: Stella
authors.initials: S
authors.lastname: Balbino
authors.affiliation: Department of Pharmacy-Drug Sciences, University of Bari Aldo Moro, Campus-Via Orabona, 4, Bari, Italy. antonio.rosato@uniba.it.
authors.forename: Antonio
authors.initials: A
authors.lastname: Rosato
authors.affiliation: Department of Biomedical Science and Human Oncology, Hygiene Section, University of Bari "Aldo Moro", Piazza Giulio Cesare 11, Bari, Italy. giuseppina.caggiano@uniba.it.
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Caggiano
mesh_terms: D000077612:Anidulafungin; D000935:Antifungal Agents / Q000494:pharmacology*; D002175:Candida / Q000187:drug effects* / Q000302:isolation & purification; D002177:Candidiasis / Q000382:microbiology*; D000077336:Caspofungin; D054714:Echinocandins / Q000494:pharmacology*; D006785:Hospitals, University; D006801:Humans; D007558:Italy; D055666:Lipopeptides / Q000494:pharmacology*; D000077551:Micafungin; D008826:Microbial Sensitivity Tests / Q000379:methods
chemical_list: D000935:Antifungal Agents; D054714:Echinocandins; D055666:Lipopeptides; D000077612:Anidulafungin; D000077336:Caspofungin; D000077551:Micafungin