Anidulafungin compared with fluconazole in severely ill patients with candidemia and other forms of invasive candidiasis: support for the 2009 IDSA treatment guidelines for candidiasis.
BACKGROUND
During the past decade, the incidence of Candida infections in hospitalized patients has increased, with fluconazole being the most commonly prescribed systemic antifungal agent for these infections. However, the 2009 Infectious Diseases Society of America (IDSA) candidiasis guidelines recommend an echinocandin for the treatment of candidemia/invasive candidiasis in patients who are considered to be "moderately severe or severely" ill. To validate these guidelines, clinical trial data were reviewed.


METHODS
A secondary analysis of data from a previously published prospective, randomized, double-blind clinical trial was performed; it compared anidulafungin with fluconazole for the treatment of invasive candidiasis and candidemia. Patients with critical illness were identified at study entry by using the following criteria: Acute Physiology and Chronic Health Evaluation (APACHE) II score of ≥ 15, evidence of severe sepsis (sepsis and one or more end-organ dysfunctions) present, and/or patient was in intensive care. Global response rates were compared at the end of intravenous study treatment (the primary end point of the original study) and all-cause mortality at 14 and 28 days from study entry in this group.


RESULTS
The patients (163 (66.5%) of 245) fulfilled at least one criterion for critical illness (anidulafungin, n = 89; fluconazole, n = 74). No significant differences were found in baseline characteristics between the two treatment groups. The global response rate was 70.8% for anidulafungin and 54.1% for fluconazole (P = 0.03; 95% confidence interval (CI): 2.0 to 31.5); all-cause mortality was 10.1% versus 20.3% at 14 days (P = 0.08; 95% CI, -0.9 to 21.3) and was 20.2% versus 24.3% at 28 days (P = 0.57; 95% CI, -8.8 to 17.0) for anidulafungin and fluconazole, respectively.


CONCLUSIONS
In this post hoc analysis, anidulafungin was more effective than fluconazole for treatment of severely ill patients with candidemia, thus supporting the 2009 IDSA guidelines.


BACKGROUND
Clinicaltrials.gov NCT00058682.
The Miller School of Medicine at the University of Miami, Jackson Memorial Hospital, 1611 NW 12th Avenue, Miami, FL 33136, USA. dkett@med.miami.edu
Daniel H
DH
Kett
Andrew F
AF
Shorr
Annette C
AC
Reboli
Arlene L
AL
Reisman
Pinaki
P
Biswas
Haran T
HT
Schlamm
D000368:Aged; D000077612:Anidulafungin; D000935:Antifungal Agents / Q000627:therapeutic use*; D058387:Candidemia / Q000188:drug therapy / Q000401:mortality; D058365:Candidiasis, Invasive / Q000188:drug therapy* / Q000401:mortality; D004311:Double-Blind Method; D054714:Echinocandins / Q000627:therapeutic use*; D005260:Female; D015725:Fluconazole / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D017410:Practice Guidelines as Topic; D011446:Prospective Studies; D012720:Severity of Illness Index; D012955:Societies, Medical; D016896:Treatment Outcome; D014481:United States
D000935:Antifungal Agents; D054714:Echinocandins; D015725:Fluconazole; D000077612:Anidulafungin