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

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. Electronic supplementary material The online version of this article (10.1007/s10096-019-03525-y) contains supplementary material, which is available to authorized users.

Evolution of clinical guidelines for antimicrobial management of Clostridioides difficile infection

“…The study showed that vancomycin and fidaxomicin are similar in terms of initial treatment response, but follow up at 90 days showed a significantly lower rate of recurrence in those who received fidaxomicin compared with vancomycin (6.2% versus 19.0%, p < 0.001). 31 This study shows that, with an alternative usage of fidaxomicin, very low rates of recurrence can be achieved. The other study used to support fidaxomicin being used preferentially ahead of vancomycin was a meta-analysis by Okumura et al including seven publications.…”

Fidaxomicin for the Treatment of Clostridioides difficile Infection in Adult Patients: An Update on Results from Randomized Controlled Trials

“…Of note, pharmacokinetic/pharmacodynamic data from patients enrolled in EXTEND revealed that fidaxomicin concentrations in stools were above the MIC 90 of C. difficile isolates (inferred from in vitro studies) until day 26 ± 1 [ 90 ]. The subgroup analyses of the EXTEND study showed higher clinical cure rates in the extended-pulsed fidaxomicin arm independent of age, prior CDI, infection with PCR-ribotype 027, CDI severity, or presence of cancer [ 91 ]. A post hoc analysis of the EXTEND study conducted after testing stools of enrolled patients at screening, also with the BioFire FilmArray Gastrointestinal Panel (BioMérieux, Basingstoke, UK), suggested that co-infection with other pathogens could possibly explain clinical failures [ 92 ].…”

Path of least recurrence: A systematic review and meta‐analysis of fidaxomicin versus vancomycin for Clostridioides difficile infection

“…Of the remaining 22 full-text articles reviewed, 14 studies (six RCTs and eight observational trials) met eligibility criteria for the final meta-analysis (Figure 1). [9][10][11][12][20][21][22][23][24][25][26][27][28][29][30] Reasons for excluding full-text articles included an unspecified follow-up period for recurrence, missing data, population overlap, and concomitant use of fecal microbiota transplantation. [31][32][33][34][35][36][37] For included RCTs, three studies were assessed to have a low risk of bias and three with some concerns, primarily due to problems related to the unblinding of standard-of-care treatments (Figure 2A).…”