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

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.