title: De-escalation from micafungin is a cost-effective alternative to traditional escalation from fluconazole in the treatment of patients with systemic Candida infections.
abstract: BACKGROUND
  Systemic Candida infections (SCI) occur predominantly in intensive care unit patients and are a common cause of morbidity and mortality. Recently, changes in Candida epidemiology with an increasing prevalence of SCI caused by Candida non-albicans species have been reported. Resistance to fluconazole and azoles in general is not uncommon for non-albicans species. Despite guidelines recommending initial treatment with broad-spectrum antifungals such as echinocandins with subsequent switch to fluconazole if isolates are sensitive (de-escalation strategy), fluconazole is still the preferred first-line antifungal (escalation) in many clinical practice settings. After diagnosis of the pathogen, the initial therapy with fluconazole is switched to a broad-spectrum antifungal if a non-albicans is identified.
  
  
  METHODS
  The cost-effectiveness of initial treatment with micafungin (de-escalation) vs fluconazole (escalation) in patients with SCI was estimated using decision analysis based on clinical and microbiological data from pertinent studies. The model horizon was 42 days, and was extrapolated to cover a lifetime horizon. All costs were analyzed from the UK NHS perspective. Several assumptions were taken to address uncertainties; the limitations of these assumptions are discussed in the article.
  
  
  RESULTS
  In patients with fluconazole-resistant isolates, initial treatment with micafungin avoids 30% more deaths and successfully treats 23% more patients than initial treatment with fluconazole, with cost savings of £1621 per treated patient. In the overall SCI population, de-escalation results in 1.2% fewer deaths at a marginal cost of £740 per patient. Over a lifetime horizon, the incremental cost-effectiveness of de-escalation vs escalation was £15,522 per life-year and £25,673 per QALY.
  
  
  CONCLUSIONS
  De-escalation from micafungin may improve clinical outcomes and overall survival, particularly among patients with fluconazole-resistant Candida strains. De-escalation from initial treatment with micafungin is a cost-effective alternative to escalation from a UK NHS perspective, with a differential cost per QALY below the 'willingness-to-pay' threshold of £30,000.
authors.affiliation: Institute of Healthcare Associated Infection, University of the West of Scotland , Ayrshire , UK.
authors.forename: Robert G
authors.initials: RG
authors.lastname: Masterton
authors.forename: Montserrat
authors.initials: M
authors.lastname: Casamayor
authors.forename: Primrose
authors.initials: P
authors.lastname: Musingarimi
authors.forename: Anke
authors.initials: A
authors.lastname: van Engen
authors.forename: Raymund
authors.initials: R
authors.lastname: Zinck
authors.forename: Olatunji
authors.initials: O
authors.lastname: Odufowora-Sita
authors.forename: Isaac A O
authors.initials: IA
authors.lastname: Odeyemi
mesh_terms: D000935:Antifungal Agents / Q000008:administration & dosage / Q000191:economics* / Q000627:therapeutic use*; D002177:Candidiasis / Q000188:drug therapy* / Q000191:economics / Q000401:mortality; D003362:Cost-Benefit Analysis; D003661:Decision Support Techniques; D054714:Echinocandins / Q000008:administration & dosage / Q000191:economics* / Q000627:therapeutic use*; D015725:Fluconazole / Q000191:economics / Q000627:therapeutic use; D006296:Health Services / Q000191:economics / Q000706:statistics & numerical data; D006801:Humans; D008017:Life Expectancy; D055666:Lipopeptides / Q000008:administration & dosage / Q000191:economics* / Q000627:therapeutic use*; D000077551:Micafungin; D008826:Microbial Sensitivity Tests; D019057:Quality-Adjusted Life Years
chemical_list: D000935:Antifungal Agents; D054714:Echinocandins; D055666:Lipopeptides; D015725:Fluconazole; D000077551:Micafungin