158 Reduced acquisition of yeast in stools of Clostridium difficile infected patients treated with fidaxomicin (FDX) compared with vancomycin (VAN)

Friday, March 19, 2010
Grand Hall (Hyatt Regency Atlanta)
Michelle M. Nerandzic, BS , Cleveland VA Medical Center, Cleveland, OH
Kathleen Mullane, MD , University of Chicago, Chicago, IL
Farah Babakhani , Optimer Pharmaceuticals, San Diego, CA
Curtis J. Donskey , Cleveland VA Medical Center, Cleveland, OH

Background: Use of oral VAN or metronidazole for treatment of Clostridium difficile infection (CDI) promotes VAN-resistant enterococci (VRE) and may also promote colonization by yeast and antibiotic-resistant bacterial pathogens due to disruption of the intestinal microflora.

Objective: We tested the hypothesis that FDX, a novel macrocyclic antibiotic, will not promote acquisition of yeast, fluoroquinolone-resistant gram-negative bacilli (FQR-GNB), and MRSA in CDI patients to the extent that oral VAN does because it lacks activity against many gut flora including Bacteroides spp.

Methods: In patients treated for CDI with FDX or VAN in a blinded phase 3 trial, a subset had stool samples cultured for yeast, FQR-GNB, MRSA and Bacteroides spp. prior to and at end of therapy (EOT).

Results: Of 302 CDI patients with baseline and EOT stools, 160 (53%) were treated with VAN and 142 (47%) with FDX. Among 252 subjects with negative initial cultures for yeast, acquisition of yeast occurred in 39 of 133 (29%) VAN-treated patients versus 23 of 119 (19%) FDX-treated patients (P <0.025). For VAN- versus FDX-treated subjects, there were no significant differences (P >0.05) in baseline frequencies of colonization with FQR-GNB (3.8% and 2.1%, respectively) and MRSA (4.4% and 4.2%, respectively) or in the rates of acquisition of FQR-GNB (2.5% and 3.5%, respectively) and MRSA (0.6% and 0%, respectively). Sixty-three percent of FDX-treated patients tested had >5 log10Bacteroides spp./g of stool at EOT versus 13% of VAN-treated patients (P=0.004).

Conclusions: Oral FDX is less likely than VAN to promote acquisition of intestinal colonization with yeast, probably due in part to relative sparing of anaerobic microflora including Bacteroides spp. in FDX-treated patients. Acquisition of FQR-GNB and MRSA intestinal colonization was uncommon in patients treated with either agent.