Fidaxomicin was the drug most likely to provide a sustained symptomatic cure for Clostridium difficile, according to a recent comparison of studied treatment options.
The random-effects network meta-analysis included 24 trials involving 5,361 patients with confirmed C. difficile. Thirteen different drugs were included, and the overall quality of evidence was rated as moderate to low. The primary outcome was sustained symptomatic cure, defined as the number of patients with resolution of diarrhea minus those with recurrence or death. Results were published by The Lancet Infectious Diseases on July 16.
The analysis found that fidaxomicin was more likely to provide sustained cure than vancomycin (odds ratio [OR], 0.67; 95% CI, 0.55 to 0.82). Teicoplanin also performed significantly better than vancomycin (OR, 0.37; 95% CI, 0.14 to 0.94), but the authors noted that the drug's results were based on studies from 1992 and 1996 with only 55 patients total and high risk of bias. Both fidaxomicin and vancomycin performed better than metronidazole (respective ORs, 0.49 [95% CI, 0.35 to 0.68] and 0.73 [95% CI, 0.56 to 0.95]). Teicoplanin, ridinilazole, and surotomycin also showed superiority to metronidazole (respective ORs, 0.27 [95% CI, 0.10 to 0.70], 0.41 [95% CI, 0.19 to 0.88], and 0.66 [95% CI, 0.45 to 0.97]). Ridinilazole is a C. difficile-specific antibiotic that is expected to enter a phase 3 trial this year, and surotomycin is another newly developed drug, the authors noted. The analysis also found that bacitracin was inferior to teicoplanin and fidaxomicin and that tolevamer was inferior to all drugs except for LFF571 and bacitracin.
Based on the results, the authors concluded, “Fidaxomicin is a better treatment option than vancomycin for all patients except those with severe infections with C. difficile and could be considered as a first-line therapy. Metronidazole should not be recommended for treatment of C. difficile.” Additionally, the authors observed that use of oral teicoplanin for C. difficile should be studied in a randomized controlled trial and that ridinilazole shows potential to be an efficacious treatment if phase 3 trials are successful. The authors noted potential limitations to the meta-analysis results, including that most of the included trials were sponsored by industry.
An accompanying editorial comment agreed that oral metronidazole shouldn't be recommended for any cases of C. difficile, regardless of severity, but added that IV metronidazole, combined with intracolonic vancomycin, could be used to treat severe C. difficile in patients unable to take oral medications. The editorial also noted that 2018 guidelines from the Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America still recommend vancomycin as the first option for treatment, despite evidence supporting fidaxomicin, “suggesting that they considered drug costs when developing their recommendations,” the editorialist said.