Extended-pulsed fidaxomicin versus vancomycin for Clostridium difficile infection: EXTEND study subgroup analyses

Eur J Clin Microbiol Infect Dis. 2019 Jun;38(6):1187-1194. doi: 10.1007/s10096-019-03525-y. Epub 2019 Mar 25.

Abstract

Poor outcomes following Clostridium difficile infection (CDI) have been associated with advanced age, presence of cancer and C. difficile PCR-ribotype 027. The impact of baseline risk factors on clinical outcomes was evaluated using data from the EXTEND study, in which rate of sustained clinical cure (SCC) in the overall population was significantly higher with an extended-pulsed fidaxomicin (EPFX) regimen than with vancomycin. Patients aged ≥ 60 years received EPFX (fidaxomicin 200 mg twice daily, days 1-5; once daily on alternate days, days 7-25) or vancomycin (125 mg four times daily, days 1-10). We analysed outcomes by advanced age, cancer diagnosis, CDI severity, prior CDI occurrence and infection with PCR-ribotype 027. The primary endpoint was SCC 30 days after end of treatment (EOT; clinical response at test-of-cure with no subsequent recurrence). SCC rates 30 days after EOT did not differ significantly between EPFX (124/177, 70.1%) and vancomycin (106/179, 59.2%) regardless of age, cancer diagnosis, CDI severity and prior CDI. In patients with PCR-ribotype 027, SCC rate 30 days after EOT was significantly higher with EPFX (20/25, 80%) than with vancomycin (9/22, 40.9%) (treatment difference, 39.1%; 95% CI, 13.2-64.9; P = 0.006). Subgroup analyses from the EXTEND study suggest that EPFX is efficacious as a potential treatment for CDI regardless of age, cancer diagnosis, infection with PCR-ribotype 027, CDI severity or prior CDI. ClinicalTrials.gov identifier: NCT02254967.

Keywords: Antibacterial agents; Clostridium difficile infection; Cohort analyses; Randomised controlled trial; Recurrence.

Publication types

  • Clinical Trial
  • Comparative Study

MeSH terms

  • Aged
  • Aged, 80 and over
  • Anti-Bacterial Agents / administration & dosage
  • Anti-Bacterial Agents / pharmacology
  • Clostridioides difficile / classification
  • Clostridioides difficile / drug effects*
  • Clostridioides difficile / genetics
  • Clostridium Infections / drug therapy*
  • Clostridium Infections / pathology
  • Feces / microbiology
  • Female
  • Fidaxomicin / administration & dosage*
  • Fidaxomicin / pharmacology*
  • Follow-Up Studies
  • Humans
  • Male
  • Middle Aged
  • Recurrence
  • Ribotyping
  • Treatment Outcome
  • Vancomycin / administration & dosage*
  • Vancomycin / pharmacology*

Substances

  • Anti-Bacterial Agents
  • Vancomycin
  • Fidaxomicin

Associated data

  • ClinicalTrials.gov/NCT02254967