A Review of the Safety and Efficacy of Vaccines as Prophylaxis for Clostridium difficile Infections

Abstract

This review aims to evaluate the literature on the safety and efficacy of novel toxoid vaccines for the prophylaxis of Clostridium difficile infections (CDI) in healthy adults. Literature searches for clinical trials were performed through MEDLINE, ClinicalTrials.gov, and Web of Science using the keywords bacterial vaccines, Clostridium difficile, and vaccine. English-language clinical trials evaluating the efficacy and/or safety of Clostridium difficile toxoid vaccines that were completed and had results posted on ClinicalTrials.gov or in a published journal article were included. Six clinical trials were included. The vaccines were associated with mild self-reported adverse reactions, most commonly injection site reactions and flu-like symptoms, and minimal serious adverse events. Five clinical trials found marked increases in antibody production in vaccinated participants following each dose of the vaccine. Clinical trials evaluating C. difficile toxoid vaccines have shown them to be well tolerated and relatively safe. Surrogate markers of efficacy (seroconversion and geometric mean antibody levels) have shown significant immune responses to a vaccination series in healthy adults, indicating that they have the potential to be used as prophylaxis for CDI. However, more research is needed to determine the clinical benefits of the vaccines.

Recommendations for the diagnosis and treatment of Clostridioides difficile infection: An official clinical practice guideline of the Spanish Society of Chemotherapy (SEQ), Spaish Society of Internal Medicine (SEMI) and the working group of Postoperative Infection of the Spanish Society of Anesthesia and Reanimation (SEDAR)

“…Vaccine candidates based on altered CD toxins A and B are currently under clinical trial study for the prevention of CDI [233,234]. Early trials suggest that some of these candidates have an acceptable safety and tolerability profile.…”

Comparing Intervention Strategies for Reducing Clostridioides difficile Transmission in Acute Healthcare Settings: An Agent-Based Modeling Study

“…We also still observe, as we did in Table 4, that targeted antibiotic reduction scenario 3 (Table 2), which targets the reduction of high-risk and very high-risk antibiotics, is best at reducing nosocomial infections. Therefore, Scenarios 7,8,9,16,17,18,25,26, and 27 affect the nosocomial infections the most.…”

“…Overall, recommendations for controlling CDI have not changed overtime. Vaccine trials have demonstrated hopeful results in clinical trials [25,26]. Although many initial vaccines focus on toxin-related antigens and do not prevent colonization by C. difficile, vaccines may be an additional tool for reducing transmission in hospital settings by decreasing number of CDI patients.…”

Prevention of Clostridium difficile Infection in Critically Ill Adults

“…Although not evaluated in the ICU setting, there may be a promising role for Clostridium spore–based vaccination. At least six clinical trials evaluating C. difficile toxoid vaccines have been conducted, with reports of significant immune responses and high tolerability in healthy adults . However, an interim analysis of the most recent phase III trial resulted in discontinuation of an experimental C. difficile vaccine in clinical development .…”

“…At least six clinical trials evaluating C. difficile toxoid vaccines have been conducted, with reports of significant immune responses and high tolerability in healthy adults. 66 However, an interim analysis of the most recent phase III trial resulted in discontinuation of an experimental C. difficile vaccine in clinical development. 67 The vaccine now furthest along the C. difficile vaccine pipeline is being evaluated in the CLOVER trial for primary prevention, a phase III placebo-controlled study expected to be completed in 2020 and enroll more than 15,000 patients (ClinicalTrials.gov identifier NCT03090191).…”