title: Efficacy of combination therapy of triazole and echinocandin in treatment of invasive aspergillosis: a systematic review of animal and human studies.
abstract: OBJECTIVE
  The effectiveness of the combination therapy of triazole and echinocandin in treatment of invasive aspergillosis (IA) remains controversial. The objective of this systematic review was to assess the efficacy of combination therapy of triazole and echinocandin in treatment of IA.
  
  
  METHODS
  Relevant articles on the combination therapy of triazole and echinocandin in IA, including the animal studies and clinical studies from January 1966 to October 2013, were searched on Web of Science, PubMed and Cochrane Library. The prolongation of survival of the combination therapy of triazole and echinocandin in IA was performed as risk ratio (RR) with 95% confidence interval (95% CI).
  
  
  RESULTS
  Nine animal studies with a total of 1,582 animals and five clinical trials totaling 872 patients were included. The survival of the included animal studies with combination therapy was significantly prolonged compared with echinocandin alone [RR =2.26, (95% CI, 1.79-2.87; P<0.00001)], but no statistical difference compared with monotherapy of triazole [RR =1.19, (95% CI, 0.98-1.44; P=0.08)]. Of the four human cohort studies, two studies observed that the combination therapy of triazole and echinocandin was associated with a significant reduction in mortality compared with other treatments, and one study might be considered as a preferable therapy [HR =0.58, (95% CI, 0.3-1.14; P=0.117)]. While another study revealed that there was no significant difference among the combination therapy of triazole and echinocandin and either of the monotherapy. In the randomized clinical trial (RCT), of the 135 patients who received the combination therapy, 39 died, while 55 died out of 142 patients who received monotherapy (P=0.08, 95% CI, -21.4, 1.09) by week 12.
  
  
  CONCLUSIONS
  The combination therapy of triazole and echinocandin in treating IA results in a trend towards improved overall survival in animals' studies and clinical studies. Well-designed RCTs and further improved clinical trials are necessary to study the effectiveness of the combination therapy.
authors.affiliation: Department of Respiratory and Critical Care Medicine, Jinling Hospital, Nanjing University School of Medicine, Nanjing 210002, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Respiratory and Critical Care Medicine, Jinling Hospital, Nanjing University School of Medicine, Nanjing 210002, China.
authors.forename: Wen-Kui
authors.initials: WK
authors.lastname: Sun
authors.affiliation: Department of Respiratory and Critical Care Medicine, Jinling Hospital, Nanjing University School of Medicine, Nanjing 210002, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Wu
authors.affiliation: Department of Respiratory and Critical Care Medicine, Jinling Hospital, Nanjing University School of Medicine, Nanjing 210002, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Chen
authors.affiliation: Department of Respiratory and Critical Care Medicine, Jinling Hospital, Nanjing University School of Medicine, Nanjing 210002, China.
authors.forename: Xiao-Yong
authors.initials: XY
authors.lastname: Xu
authors.affiliation: Department of Respiratory and Critical Care Medicine, Jinling Hospital, Nanjing University School of Medicine, Nanjing 210002, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Su
authors.affiliation: Department of Respiratory and Critical Care Medicine, Jinling Hospital, Nanjing University School of Medicine, Nanjing 210002, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Shi
keywords: Triazole; echinocandin; invasive aspergillosis (IA); systematic review