Relapse Versus Reinfection: Recurrent Clostridium difficile Infection Following Treatment With Fidaxomicin or Vancomycin

Abstract

Our study sought to compare the strain types of Clostridium difficile causing initial and recurrent episodes of C. difficile infection (CDI) in adult patients with a first episode of CDI or 1 prior episode of CDI within the previous 90 days. Strains originated from patients who had been entered into two phase 3 randomized clinical trials of fidaxomicin versus vancomycin. Isolates of C. difficile from the initial and recurrent episodes within 28 (±2) days of cure of CDI were compared using restriction endonuclease analysis (REA) typing. Paired isolates were available from 90 of 194 (46%) patients with recurrent CDI. Patients with isolates available were significantly younger ( P = .008) and more likely to be from Canadian sites ( P = .0001), compared with patients without isolates. In 75 of 90 subjects (83.3%), the identical REA type strain was identified at recurrence and the initial episode (putative relapse). Early recurrences (0–14 days after treatment completion) were relapses in 86.7% and a new strain (reinfection) in 13.3%. Later recurrences (15–31 days after treatment) were relapses in 76.7% and reinfections in 23.3%. Mean time (± standard deviation) to recurrence was 12.2 (±6.4) days for relapses and 14.7 (±6.8) days for reinfections ( P = .177). The most common BI/NAP1/027 group and the previous US epidemic REA group J/NAP2/001 had a significantly higher combined rate of recurrence with the same strain (relapse), compared with the other REA groups (39 of 42 [93%] vs 36 of 48 [75%], respectively; P = .023). We found a higher than historic rate of recurrent CDI caused by the same isolate as the original episode, a finding that may be related to the relatively short observation period in this study and the high frequency of isolation of epidemic strains, such as groups BI and J, for which relapse rates may be higher than for other REA groups. Caution in generalizing these observations is required, because the patients studied were younger and more likely to be from Canadian sites than were patients with recurrence who did not provide isolates. Clinical Trials Registration. NCT00314951 and NCT00468728.

Association of Relapse of Clostridium difficile Disease with BI/NAP1/027

“…This finding is consistent with a recent point-prevalence investigation of C. difficile environmental contamination in a hos- MLVA is an objective, highly discriminatory molecular genotyping tool that can be used to define relapse versus reinfection in recurrent CDI cases. We report rates of relapse in our study that were lower than the rates in recent reports that used PCR-ribotyping, multilocus sequence typing (MLST), and REA to classify recurrent CDI (7,8,13). These methods may overestimate relapse and underestimate reinfection rates because they are less discriminatory than MLVA (14).…”

“…Two very recent studies have described increased recurrence rates and a trend toward a higher incidence of relapse among patients infected with BI strains as defined by REA typing (8,26). These data could have major implications for treatment and development of new therapeutics that specifically target infection with BI/NAP1/027 strains.…”

“…However, some of the molecular typing methods used in these studies such as PCR-ribotyping and random amplification of polymorphic DNAs (RAPD) lack sufficient discriminatory power and may have misclassified reinfections as relapses. In a study using restriction endonuclease analysis (REA), 83.3% of recurrences were due to relapse (8). In this study, multilocus variable-number tandemrepeat analysis (MLVA), a highly discriminatory C. difficile genotyping method, was used to define relapse in patients with recurrent CDI and to identify risk factors associated with relapse.…”

An Unusual Case of Clostridium difficile Infection in Trinidad and Tobago

“…Patients usually present with fever, abdominal pain, diarrhea, loss of appetite and fatigue [20]. Clostridium difficile-associated diarrhea seems to be on the increase and is implicated in 20-30% of all antibiotic associated diarrheal cases [21]. Fatal cases caused by toxin A and B producing Clostridium difficile strains, have been reported in countries such as, Canada, United States and Europe [7,11,14,22].…”

Multicenter Evaluation of the Verigene Clostridium difficile Nucleic Acid Assay

“…Likewise, there are no formal recommendations to alter treatment based solely on the strain causing the infection. Some strain types may correlate with an increased risk of recurrent disease (23). In the initial fidaxomicin treatment study, the data showed that the risk of relapse may vary depending upon the C. difficile strain type (24).…”