title: Caspofungin activity against clinical isolates of azole cross-resistant Candida glabrata overexpressing efflux pump genes.
abstract: OBJECTIVE
  Several studies have documented the potent in vitro activity of caspofungin against Candida spp. This is of special concern for Candida glabrata infections that are often resistant to many azole antifungal agents and, consequently, difficult to treat. The aim of the present study was to expand the data on the in vitro activity of caspofungin against azole-resistant isolates of C. glabrata.
  
  
  METHODS
  A total of 50 clinical isolates of C. glabrata were tested for susceptibility to caspofungin. The isolates were cross-resistant to multiple azoles, including fluconazole, itraconazole, ketoconazole and voriconazole. Expression of the resistance-related CgCDR1 and CgCDR2 genes was evaluated by quantitative RT-PCR analysis. The MICs of caspofungin were determined by using the National Committee for Clinical Laboratory Standards M27-A2 reference method.
  
  
  RESULTS
  C. glabrata isolates exhibited increased expression of the CDR efflux pump(s), and this was in accordance with their high-level azole resistance. In contrast, all the isolates were highly susceptible to caspofungin (100% of isolates were inhibited at <or=1 mg/L).
  
  
  CONCLUSIONS
  Our results represent further evidence for the excellent antifungal potency of caspofungin, particularly against C. glabrata isolates expressing cross-resistance to azoles.
authors.affiliation: Istituto di Microbiologia, Università Cattolica del Sacro Cuore, Rome, Italy, and Institut de Microbiologie, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland.
authors.forename: Brunella
authors.initials: B
authors.lastname: Posteraro
authors.forename: Maurizio
authors.initials: M
authors.lastname: Sanguinetti
authors.forename: Barbara
authors.initials: B
authors.lastname: Fiori
authors.forename: Marilena
authors.initials: M
authors.lastname: La Sorda
authors.forename: Teresa
authors.initials: T
authors.lastname: Spanu
authors.forename: Dominique
authors.initials: D
authors.lastname: Sanglard
authors.forename: Giovanni
authors.initials: G
authors.lastname: Fadda
mesh_terms: D000935:Antifungal Agents / Q000494:pharmacology*; D001393:Azoles / Q000494:pharmacology*; D001693:Biological Transport, Active / Q000235:genetics; D041221:Candida glabrata / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D000077336:Caspofungin; D025141:Drug Resistance, Fungal / Q000235:genetics*; D054714:Echinocandins; D015870:Gene Expression; D006801:Humans; D055666:Lipopeptides; D008826:Microbial Sensitivity Tests; D010456:Peptides, Cyclic / Q000494:pharmacology*; D012331:RNA, Fungal / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D000935:Antifungal Agents; D001393:Azoles; D054714:Echinocandins; D055666:Lipopeptides; D010456:Peptides, Cyclic; D012331:RNA, Fungal; D000077336:Caspofungin