1633. A marginal structural approach to measuring the comparative effectiveness of echinocandins vs. fluconazole therapy for the treatment of adult candidemia (MSG-12)
Session: Poster Abstract Session: Mycology - There's a Fungus Among Us: Treatment
Friday, October 28, 2016
Room: Poster Hall
Background: Based on patient level analysis of randomized controlled trial data the Infectious Diseases Society of America guidelines support echinocandins as the first line therapy for candidemia, but observational data confirming the benefit of echinocandins in real world settings are lacking. Existing reports are limited by intention to treat approaches that ignore time varying confounding and assume no loss to follow up (LTF) biasing treatment effect estimates.

Methods: A US observational cohort of incident adult inpatient episodes of candidemia from 2009-2013 was assembled using Premier PerspectiveTM, a multicenter inpatient database. Patients transferred from an outside institution or dying within 3 days of the blood culture draw were excluded. We compared 30-day mortality following initial therapy with an echinocandin versus fluconazole using both logistic regression as well as a marginal structural model (MS model). MS model employed both inverse probability of treatment and censoring weights to control for time varying confounders and differential LTF. Covariates included in these models are detailed in Table 1.

Results: The cohort included 2014 admissions with candidemia; 45.6% and 54.4% received fluconazole and an echinocandin as initial therapy, respectively. The 30-day mortality was 13.5%. While standard logistic regression suggested an increased 30-day mortality risk for patients initiated on echinocandins, MS model found echinocandins to be associated with a reduced risk of death at 30 days.

Conclusion: Using a MS model, which accounted for time varying confounding and differential LTF, initial therapy with an echinocandin was associated with decreased risk for mortality. These results highlight the importance of leveraging such analytic models when daily therapy choices are based on a patient’s clinical status and when LTF is variable and informative.

 Table 1. Regression Model Results

Odds Ratio (95% CI)

Logistic Regression

Unadjusted

1.76 (1.35-2.31)

Multivariablea

1.49 (1.11-1.99)

MS Modelb

0.65(0.59-0.72)

AAdjusted for age, gender, baseline vasopressor use, receipt of empiric antifungal therapy, and hospital.

BAdjusted for covariates above and daily time varying exposure to vasopressor and antifungal therapy.

MS Model also accounted for differential LTF by baseline and time varying covariates.

Laura Anatale-Tardiff, MPH1, Kelly Getz, PhD, MPH2, Rui Xiao, PhD3, John Baddley, MD4, Luis Ostrosky-Zeichner, MD, FIDSA, FSHEA5, Peter Pappas, MD6, Theoklis Zaoutis, MD, MSCE7 and Brian Fisher, DO, MPH, MSCE7, (1)Infectious Diseases, Children's Hospital of Philadelphia, Philadelphia, PA, (2)Division of Oncology, Children's Hospital of Philadelphia, Philadelphia, PA, (3)Department of Biostatistics and Epidemiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, (4)Infectious Diseases, University of Alabama at Birmingham, Birmingham, AL, (5)University of Texas Medical School at Houston, Houston, TX, (6)Division of Infectious Disease, University of Alabama at Birmingham, Birmingham, AL, (7)The Children's Hospital of Philadelphia, Philadelphia, PA

Disclosures:

L. Anatale-Tardiff, None

K. Getz, None

R. Xiao, None

J. Baddley, Pfizer: Consultant , Consulting fee
Merck: Consultant , Salary

L. Ostrosky-Zeichner, Astellas: Consultant and Investigator , Consulting fee and Research grant
Merck: Non-branded educational speaker and Scientific Advisor , Consulting fee and Speaker honorarium
Pfizer: Investigator and Non-branded educational speaker , Research grant and Speaker honorarium
Cidara: Scientific Advisor , Consulting fee
Scynexis: Investigator and Scientific Advisor , Consulting fee and Grant recipient

P. Pappas, Merck: Grant Investigator , Grant recipient
Astellas: Grant Investigator , Grant recipient
Gilead: Grant Investigator , Grant recipient
T2 Biosystems: Grant Investigator and Scientific Advisor , Consulting fee and Grant recipient
IMMY: Grant Investigator , Grant recipient
Viamet: Scientific Advisor , Consulting fee
Vical: Scientific Advisor , Consulting fee
Matinas: Scientific Advisor , Consulting fee
Amplyxx: Scientific Advisor , Consulting fee

T. Zaoutis, merck: Grant Investigator , Research grant

B. Fisher, Pfizer: Grant Investigator , Research grant
Merck: Grant Investigator , Research grant
Ansun BioPharma: Research Contractor , Research grant

Findings in the abstracts are embargoed until 12:01 a.m. CDT, Wednesday Oct. 26th with the exception of research findings presented at the IDWeek press conferences.