Recurrent Clostridium difficile disease is a huge problem—a nightmare for patients, and a recalcitrant challenge for clinicians and infection preventionists. So this week’s New England Journal of Medicine brings good news about fidaxomicin*, a new nonabsorbable macrocyclic antibiotic active against C. difficile. In a head-to-head trial with vancomycin, cure rates were equivalent but recurrence rates were significantly lower for fidaxomicin (15% versus 25% for vancomycin, in the modified intent-to-treat groups). Unfortunately, this difference held only for non-NAP1 strains. For the nasty, hypervirulent NAP1/BI strain, recurrence rates were 24% in both groups—meaning that for the majority (64%) of patients with other strain types, the difference in recurrence rates between fidaxomicin and vancomycin was even greater (7.8% vs. 25.5%).
Why? Fidaxomicin is more active against C. difficile (bactericidal rather than bacteriostatic), has a longer post-antibiotic effect, and is slightly narrower in spectrum than vancomycin. So it probably kills C. difficile better, for longer, and without as much disruption of the rest of the colonic flora. Further studies will be needed to investigate this further, and to determine why this effect is not seen with the NAP1/BI strain.
The accompanying editorial by Dr. Herbert DuPont is well worth reading, and raises questions about whether our initial therapy for C. difficile is too short in duration (in this study, 10 day treatment courses were used), and whether we’ll eventually be using a combination of antibiotics and immunotherapy to effectively treat and prevent C. difficile recurrences. That is, if stool transplants haven’t become the treatment of choice by then.
*This drug is made by Optimer Pharmaceuticals, and all of the authors have listed disclosures at the end of the article—three of the authors are Optimer employees