title: Examination of the in vitro fungicidal activity of echinocandins against Candida lusitaniae by time-killing methods.
abstract: OBJECTIVE
  Candida lusitaniae fungaemia, although infrequent (1%), is more common in immunocompromised patients than Candida albicans. Although infections produced by Candida spp. are therapeutic targets for treatment with echinocandins, little information is available regarding their killing kinetics against C. lusitaniae. The objectives of this study were to determine the killing kinetics of anidulafungin, micafungin and caspofungin against four blood isolates of C. lusitaniae by time-kill methodology.
  
  
  METHODS
  Time-kill studies were performed in RMPI 1640 medium (5 mL, inoculum ∼10(5) cfu/mL). The number of cfu/mL was determined at 0, 2, 4, 6 and 24 h. The anidulafungin concentrations assayed were 0.03, 0.12, 0.5, 2 and 8 mg/L, while micafungin and caspofungin concentrations were 0.25, 1, 4, 16 and 32 mg/L.
  
  
  RESULTS
  MIC ranges were 0.03-1 mg/L (anidulafungin), 0.016-0.06 mg/L (micafungin) and 0.03-1 mg/L (caspofungin). The mean maximum log decrease in cfu/mL was reached with 2 mg/L anidulafungin (1.85   ± 0.4 log), 32 mg/L caspofungin (5.5 ± 0.2 log) and 32 mg/L micafungin (2.65 ± 1.9 log). Only caspofungin and micafungin reached the fungicidal endpoint (99.9% growth reduction or a 3 log decrease) with 32 mg/L at 22.8 h (caspofungin) and 26.5 h (micafungin). Analysis of variance showed significant differences in killing activity among isolates, but not among concentrations reached in serum or echinocandins.
  
  
  CONCLUSIONS
  Anidulafungin and micafungin exhibit greater killing rates than caspofungin. Caspofungin was the only echinocandin that reached the fungicidal endpoint before 24 h, but at drug concentrations (≥ 16 mg/L) not usually reached in serum. The echinocandin killing rate was isolate dependent and concentration independent.
authors.affiliation: Unidad de Microbiología Experimental, Centro de Investigación, Hospital Universitario y Politécnico La Fe, Valencia 46009, Spain. canton_emi@gva.es
authors.forename: Emilia
authors.initials: E
authors.lastname: Cantón
authors.forename: Javier
authors.initials: J
authors.lastname: Pemán
authors.forename: David
authors.initials: D
authors.lastname: Hervás
authors.forename: Ana
authors.initials: A
authors.lastname: Espinel-Ingroff
mesh_terms: D000077612:Anidulafungin; D000935:Antifungal Agents / Q000494:pharmacology*; D002175:Candida / Q000187:drug effects* / Q000502:physiology*; D000077336:Caspofungin; D015169:Colony Count, Microbial; D054714:Echinocandins / Q000494:pharmacology*; D006801:Humans; D055666:Lipopeptides / Q000494:pharmacology*; D000077551:Micafungin; D050296:Microbial Viability / Q000187:drug effects*; D013997:Time Factors
chemical_list: D000935:Antifungal Agents; D054714:Echinocandins; D055666:Lipopeptides; D000077612:Anidulafungin; D000077336:Caspofungin; D000077551:Micafungin