title: Empiric treatment against invasive fungal diseases in febrile neutropenic patients: a systematic review and network meta-analysis.
abstract: The most optimal antifungal agent for empiric treatment of invasive fungal diseases (IFDs) in febrile neutropenia is controversial. Our objective was evaluate the relative efficacy of antifungals for all-cause mortality, fungal infection-related mortality and treatment response in this population.
  
  
  
  Pubmed, Embase and Cochrane Library were searched to identify randomized controlled trials (RCTs). Two reviewers performed the quality assessment and extracted data independently. Pairwise meta-analysis and network meta-analysis were conducted to compare the antifungals.
  
  
  
  Seventeen RCTs involving 4583 patients were included. Risk of bias of included studies was moderate. Pairwise meta-analysis indicated the treatment response rate of itraconazole was significantly better than conventional amphotericin B (RR = 1.33, 95%CI 1.10-1.61). Network meta-analysis showed that amphotericin B lipid complex, conventional amphotericin B, liposomal amphotericin B, itraconazole and voriconazole had a significantly lower rate of fungal infection-related mortality than no antifungal treatment. Other differences in outcomes among antifungals were not statistically significant. From the rank probability plot, caspofungin appeared to be the most effective agent for all-cause mortality and fungal infection-related mortality, whereas micafungin tended to be superior for treatment response. The results were stable after excluding RCTs with high risk of bias, whereas micafungin had the lowest fungal infection-related mortality.
  
  
  
  Our results highlighted the necessity of empiric antifungal treatment and indicates that echinocandins appeared to be the most effective agents for empiric treatment of febrile neutropenic patients based on mortality and treatment response. However, more studies are needed to determine the best antifungal agent for empiric treatment. Our systematic review has been prospectively registered in PROSPERO and the registration number was CRD42015026629.
authors.affiliation: Department of Pharmacy, Peking University Third Hospital, Beijing, 100191, China.
authors.forename: Ken
authors.initials: K
authors.lastname: Chen
authors.affiliation: Evidence Based Medicine Center, School of Basic Medical Sciences, Lanzhou University, Lanzhou, 730000, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Duke University Division of Pulmonary, Allergy, and Critical Care Medicine, Duke University School of Medicine, Durham, NC, 27705, USA.
authors.forename: Roy A
authors.initials: RA
authors.lastname: Pleasants
authors.affiliation: Evidence Based Medicine Center, School of Basic Medical Sciences, Lanzhou University, Lanzhou, 730000, China.
authors.forename: Long
authors.initials: L
authors.lastname: Ge
authors.affiliation: Department of Pharmacy, Peking University Third Hospital, Beijing, 100191, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.affiliation: School of Basic Medical Sciences, Peking University Health Science Center, Beijing, 100191, China.
authors.forename: Kangning
authors.initials: K
authors.lastname: Peng
authors.affiliation: Department of Pharmacy, Peking University Third Hospital, Beijing, 100191, China. zhaisuodi@163.com.
authors.forename: Suodi
authors.initials: S
authors.lastname: Zhai
mesh_terms: D000935:Antifungal Agents / Q000627:therapeutic use*; D064147:Febrile Neutropenia / Q000382:microbiology* / Q000401:mortality; D006801:Humans; D000072742:Invasive Fungal Infections / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology / Q000401:mortality; D015233:Models, Statistical; D016896:Treatment Outcome
chemical_list: D000935:Antifungal Agents
keywords: Antifungals; Empiric therapy; Febrile neutropenia; Network meta-analysis; Systematic review