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Age, presence of toxin B antibodies influence C. difficile recurrence
A recent analysis suggests Clostridium difficile infection patients aged at least 65 years are at greater risk of recurrence, while those with serum anti-toxin B antibodies appear to be protected from additional episodes.
“Currently, there is no consistently effective treatment to prevent recurrent [C. difficile infection (CDI)], and no therapies have been licensed for this use,” Swati B. Gupta, DrPH, MPH, executive director, public health and scientific affairs at Merck, and colleagues wrote. “Thus, the management of these patients is often challenging, and CDI remains an important public health burden. Expanding our knowledge of the risk factors for CDI recurrence will aid clinical development of targeted therapies for patients at increased risk for recurrent CDI-related mortality and increased hospital costs.”
Gupta and colleagues reviewed data from a 2010 phase 2 study examining the impact of monoclonal antibody treatments on patients with recent CDI taking metronidazole or vancomycin. Using the study’s placebo arm as a cohort (n = 99), they analyzed a number of baseline variables to identify any associations with recurring CDI, such as race, underlying disease, initial therapy and the presence of antibodies. The primary study outcome was laboratory-documented infection recurrence within 84 days of placebo administration.
Approximately one-quarter of the placebo cohort had recurrent infection within the follow-up period. Seventy-two percent of the cohort was female, 85% were white, and 33% had a history of recurring CDI. The mean age of the cohort was 64 years.
Multivariate analysis revealed recurrence to be more common among those aged at least 65 years (OR = 3.76; P = .024). The presence of serum anti-toxin B antibodies appeared to be protective (OR = 0.11; P = .05), while anti-toxin A antibodies did not show any significant associations.
Although Gupta and colleagues advocated for additional investigation into recurrence risk factors, they said these limited findings support the potential effectiveness of a toxin B-specific monoclonal antibody treatment such as bezlotoxumab (Merck), the approval decision for which was recently delayed by the FDA.
“Results of two phase 3 trials [MODIFY I and MODIFY II] confirmed that bezlotoxumab was superior to placebo in preventing CDI recurrence and that addition of actoxumab (fully human monoclonal antibody against C. difficile toxin A) did not have any efficacy benefits over treatment with bezlotoxumab alone,” they wrote. “Results from our study support these findings and provide additional evidence for the protective effects of antibody to toxin B in the prevention of CDI recurrence.”
According to Oliver A. Cornely, MD, FACP, and Maria J.G.T. Vehreschild, DrMed, both of the University Hospital of Cologne, these findings could help guide precision treatments for CDI and recurrence, but highlight the growing need for a validated and commercially available antibody diagnostic.
“Reliable prediction models allowing for targeted treatment of patients at risk of recurrence are within reach,” they wrote in an accompanying editorial. “However, structural hurdles including lack of a commercially available endogenous toxin B antibody test, high pricing and limited reimbursement of novel CDI therapies may jeopardize successful improvement of patient care.” – by Dave Muoio
Disclosures: Gupta is an employee of Merck, the manufacturer of bezlotoxumab, and reports holding stock or stock options with the company. Please see the full studies for Cornely, Vehreschild and all other authors’ relevant financial disclosures.