title: Efficacy of the combination of voriconazole and caspofungin in experimental pulmonary aspergillosis by different Aspergillus species.
abstract: OBJECTIVE
  Invasive pulmonary aspergillosis (IPA) caused by Aspergillus fumigatus, Aspergillus flavus, or Aspergillus niger is associated with high mortality. We evaluated the efficacy and compared the therapeutic effect differences of voriconazole (VRC) in combination with caspofungin (CAS) in transiently neutropenic rats infected by A. fumigatus, A. flavus, or A. niger.
  
  
  METHODS
  Treatment groups consisted of VRC (10 mg/kg q12 h) monotherapy, CAS (1 mg/kg/day) monotherapy, combination of VRC (10 mg/kg q12 h) + CAS (1 mg/kg/day), and no drug for 10 consecutive days. The efficacy and the difference in the treatments were evaluated through prolongation of survival, reduction in serum galactomannan levels and residual fungal burden, and histological studies.
  
  
  RESULTS
  For all the strains, the combination of VRC and CAS led to significant prolongation in survival (P < 0.05) and reduction in residual fungal burden (P < 0.05) compared with CAS alone, and decrease in serum galactomannan levels (P < 0.05) compared with either agent alone. The survival in the combined therapy groups was significantly improved compared to VRC monotherapy for the strains of A. flavus and A. niger (P < 0.05), but no significant difference for the strains of A. fumigatus (P > 0.05).
  
  
  CONCLUSIONS
  Combination of VRC and CAS was synergistic in IPA by A. flavus and A. niger, but small efficacy benefits in IPA by A. fumigatus.
authors.affiliation: Department of Respiratory and Critical Care Medicine, Jinling Hospital, Nanjing University School of Medicine, 305 East Zhongshan Road, Nanjing, 210002, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Zhang
authors.forename: Xin
authors.initials: X
authors.lastname: Su
authors.forename: Wen-Kui
authors.initials: WK
authors.lastname: Sun
authors.forename: Fei
authors.initials: F
authors.lastname: Chen
authors.forename: Xiao-Yong
authors.initials: XY
authors.lastname: Xu
authors.forename: Yi
authors.initials: Y
authors.lastname: Shi
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000627:therapeutic use*; D001231:Aspergillus flavus / Q000187:drug effects; D001232:Aspergillus fumigatus / Q000187:drug effects; D001234:Aspergillus niger / Q000187:drug effects; D000077336:Caspofungin; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D054714:Echinocandins / Q000627:therapeutic use*; D005690:Galactose / Q000031:analogs & derivatives; D006801:Humans; D055666:Lipopeptides; D008297:Male; D008351:Mannans / Q000097:blood; D008826:Microbial Sensitivity Tests; D009503:Neutropenia; D055732:Pulmonary Aspergillosis / Q000188:drug therapy* / Q000382:microbiology / Q000401:mortality; D011743:Pyrimidines / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016896:Treatment Outcome; D014230:Triazoles / Q000627:therapeutic use*; D065819:Voriconazole
chemical_list: D000935:Antifungal Agents; D054714:Echinocandins; D055666:Lipopeptides; D008351:Mannans; D011743:Pyrimidines; D014230:Triazoles; C012990:galactomannan; D000077336:Caspofungin; D065819:Voriconazole; D005690:Galactose