759. Renal Impairment and Response to Fidaxomicin versus Vancomycin in Patients with Clostridium difficile Infection
Session: Oral Abstract Session: Clostridium difficile: Detection, Transmission, and Treatment
Friday, October 21, 2011: 3:45 PM
Room: 151AB
Background:  A few studies have linked chronic renal disease to increased risk and poor outcomes in Clostridium difficile infection (CDI). We studied renal function and clinical outcomes in a large database of CDI patients treated with fidaxomicin (FDX) or vancomycin (VAN).

Methods:  Patients with toxin-positive CDI were randomized to receive FDX 400 mg/d or VAN 500 mg/d for 10 d. Creatinine clearance (CrCl) prior to the first dose of study drug was calculated and renal impairment (RI) was categorized as none/normal (≥90 mL/min/1.73 m2), mild (60-89), moderate (30-59), or severe (<30). Endpoints were cure, recurrence (return of symptoms within 28 days of completing successful therapy), and time to resolution of diarrhea (TTROD). Univariate and multivariate analyses compared endpoints by treatment and level of RI.

Results:  Of 1031 patients, 57% had abnormal renal function. RI was mild in 27%, moderate in 21%, and severe in 9% of patients. Cure rate was unaffected by mild RI (91% for normal and 92% for mild RI), but declined to 80% for moderate and 74% for severe RI (p<0.001 for trend). Median TTROD increased from 56 h for normal and mild RI to 68 h and 106 h in patients with moderate and severe RI, respectively (log rank p=0.007 ). All cause mortality increased progressively with degree of RI from 2.9% in patients with normal CrCl to 17.4% in patients with severe RI (p<0.001 for trend). Cure rates were similar for FDX and VAN at each impairment level. Following cure, recurrence rates were 16%, 20%, 27%, and 25% for normal, mild, moderate, and severe RI. FDX was superior to VAN in preventing recurrence at all levels of renal function (p<0.05), and the absolute difference in recurrence rates between treatments increased with level of RI from 10% (11% FDX, 21% VAN) in patients with normal renal function to 21% (15% FDX, 35% VAN) in patients with severe impairment. By multivariate analysis, treatment arm and moderate to severe RI were significant predictors of recurrence, while age and WBC >15×109/L were not.

Conclusion:  Clinical outcomes deteriorated progressively with declining renal function. Treatment with FDX was associated with significantly lower rates of recurrence than VAN across all levels of renal function and was 58% lower in patients with severe RI.

Subject Category: C. Clinical studies of bacterial infections and antibacterials including sexually transmitted diseases and mycobacterial infections (surveys, epidemiology, and clinical trials)

Kathleen Mullane, DO, FIDSA, University of Chicago, Chicago, IL, Yoav Golan, MD MS, Tufts-New England Medical Center, Boston, MA, Derrick Crook, MB BCh, University of Oxford NIHR Oxford Biomedical Research Centre, Oxford, United Kingdom, Oliver Cornely, MD, FIDSA, Universität Köln, Cologne, Germany, Mark Miller, MD, MSc, Dept. of Microbiol. and Div. of Infectious Diseases, SMBD Jewish General Hosp., Montreal, QC, Canada, Thomas Louie, M D, University of Calgary, Calgary, AB, Canada and Sherwood Gorbach, MD, FIDSA, Tufts University School of Medicine, Boston, MA


K. Mullane, None

Y. Golan, None

D. Crook, Optimer: Investigator, Research grant

O. Cornely, Optimer: Investigator, Research support

M. Miller, None

T. Louie, None

S. Gorbach, Optimer: Board Member, Salary

Findings in the abstracts are embargoed until 12:01 a.m. EST Thursday, Oct. 20 with the exception of research findings presented at IDSA press conferences.