ABSTRACTClostridium difficile
-associated diarrhea has been associated with disruption of the normal intestinal microbiota, particularly the
Bacteroides fragilis
group and
Prevotella
species. Surotomycin is a bactericidal cyclic lipopeptide in development for treatment of
Clostridium difficile
-associated diarrhea that has selective and potent activity against
C. difficile
and other Gram-positive bacteria and a minimal impact on intestinal Gram-negative organisms. The impacts of ascending doses of surotomycin on major organism groups in the gut microbiota of healthy volunteers were evaluated during a randomized, double-blind, placebo-controlled, multiple-dose phase 1 study. Thirty volunteers were randomized into 3 cohorts, using a 4:1 ratio, to receive 250 mg, 500 mg, or 1,000 mg of surotomycin, or placebo, twice daily for 14 days. Stool samples collected at baseline (days 0 and 1) and at the end of treatment (days 13 to 15) were cultured quantitatively. The
B. fragilis
group, the
Bacteroides
/
Prevotella
group, and
Enterobacteriaceae
were also quantified by quantitative real-time PCR. Baseline and end-of-treatment stool samples showed 1- to 2-log
10
CFU/g reductions in total bacterial counts for most volunteers. Various decreases in clostridial,
Lactobacillus-Bifidobacterium
group, and enterococcus-streptococcus group counts occurred while patients were receiving surotomycin, whereas the enterobacteria and the
B. fragilis
group persisted at the end of treatment. There was no change in enterococcus MICs of surotomycin, nor was vancomycin-resistant
Enterococcus
detected after exposure. Surotomycin at doses of up to 1,000 mg twice daily had only modest disruptive effects on the gut microbiota. The potential sparing of the gut microbiota by surotomycin may decrease the risk of disease recurrence.