Editorial Commentary: The Trials and Tribulations of Treating Clostridium difficile Infection--One Step Backward, One Step Forward, but Still Progress

(See the Major Article by Johnson et al on pages 345–54.) Almost a decade ago, an editorial discussing the evidence concerning whether metronidazole was as efficacious as vancomycin for the treatment of Clostridium difficile infection (CDI) was published in the Journal. The author highlighted the need for larger, randomized prospective trials of both existing and new drugs [1]. This call has been answered, and while the primary intended outcome failed, progress has been made [2]. The report by Johnson and co-workers in this issue of Clinical Infectious Diseases represents another damaging blow to the case for metronidazole [2]. Ironically, the latest punch was landed in a contest between a novel toxin-binding polymer, tolevamer, and 2 old antibiotics. I say “ironically” because nonantibiotic treatment options for CDI carry a theoretically plausible advantage over agents that may add further deleterious effects to an already reeling gut microbiome; that is, staggering due to exposure to CDI-inciting antimicrobial(s). However, despite promising phase 2 results [3], tolevamer failed by a large margin in comparison with either metronidazole or vancomycin in phase 3 studies [2]. All was not lost, however, as the old antibiotic contenders threw up further compelling evidence that they are not equals [2].