A Review of the Safety and Efficacy of Vaccines as Prophylaxis for Clostridium difficile Infections
Abstract
:1. Introduction
2. Materials and Methods
3. Results
Summary of Trials
4. Discussion
5. Conclusions
Acknowledgments
Author Contributions
Conflicts of Interest
References
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Trial | Collection Period (Days) | ARs and AEs Reported |
---|---|---|
Kotloff et al. [17] | 7 (after each dose) | Rash (26.7%) Pain at injection site (60%; more common with adjuvant, p = 0.004) Abdominal pain (20%) Malaise (16.7%) Swelling & erythema (increased with dose; p < 0.001, p = 0.04) |
Bezay et al. [18] | 7 (after each dose) | 18–65 cohort – Pain at injection site (21%, p = 0.001) 1 |
Greenberg et al. [19] | 7 (after each dose) | 18–55 cohort – Pain (85–100%), erythema (42–50%), swelling (15–25%) & induration (8–33%) at injection site ≥65 cohort – Pain (33–67%) & erythema (8–25%) at injection site Increased eosinophil count (25–42%) Fatigue (17–25%) |
de Bruyn et al. [20] | ARs: 6 (after each dose) AEs: 30 (after each dose) | Pain at injection site (42.4–68.3%) Myalgia (33.3–45%) Malaise (29–33.7%) Headache (27.3–35.6%) Arthralgia (20.2–30%) |
Sheldon et al. [21] | ARs: 7 (after each dose) AEs: 365 (after 1st dose) | 50–64 & 65–85 cohort Pain at injection site (lasting 1–2 days) Headache (1–3 days) Fatigue (1–3 days) Upper respiratory tract infection |
Pfizer [16] | 7 (after 1st dose) 14 (after 2nd, 3rd dose) | 50–64 cohort 2 Pain (16.7–66.7%), erythema (5.6–50%) & swelling (16.7–33.3%) at injection site Headache (5.6–33.3%) Fatigue (11.1–38.9%) 65–85 cohort 2 Pain (24.6–66%), erythema (6.7–30%) & swelling (3.3–26.4%) at injection site Headache (8.3–26.4%) Fatigue (8.3–39.6%) New/worsening muscle or joint pain (0–26.4%) |
Trial | Trial Design | N | Participant Age (Years) | Efficacy Results |
---|---|---|---|---|
Kotloff et al. [17] | Sequential assignment, double-blind, phase 1 trial | 30 | 23 | Seroconversion Rates: 100% of participants in the 25 and 100 mcg dose groups 80% of participants in the 6.25 mcg dose group |
Bezay et al. [18] | Multi-center, open label, partially randomized, phase 1 trial | 140 | 30.8 (Part A) 68.3 (Part B) | Seroconversion Rates (for 75 mcg non-Alum dose group): Part A––By day 28: 70% of participants and 80% of participants (to Toxin A and B, respectively) Part B––By day 56: 91% of participants and 55% of participants (to Toxin A and B, respectively) |
Greenberg et al. [19] | Two randomized, placebo-controlled, double-blind, phase 1 trials | 98 | 18–55 (cohort 1) ≥65(cohort 2) | Seroconversion Rates: Cohort 1––By day 56: 100% of participants who received any dose of vaccine Cohort 2––By day 56: 50%, 89%, and 100% of participants who received any dose of vaccine (2, 10, 50 mcg, respectively) Placebo––0% of participants at all time points |
de Bruyn et al. [20] | Multi-center, Placebo-controlled, randomized, phase 2 trial performed in 2 stages | 661 | 40–64 (cohort 1) 65–75 (cohort 2) | Highest Seroconversion Rates: By day 60: 97% of participants who received 100 mcg with Alum By day 60: 93.2% of participants who received 100 mcg non-Alum |
Sheldon et al. [21] | Placebo-controlled, randomized, observer-blinded phase 1 trial | 192 | 50–64 (cohort 1) 65–85 (cohort 2) | GMFRs: Cohort 1––By 7 months (day 210): GMFR = 59–149.23 and 116.67–2503.75 compared to 2.47 and 2.48 in placebo groups (to Toxin A and B, respectively) Cohort 2––By 7 months (day 210): GMFR = 42.73–254.77 and 136.12–4922.8 compared to 2.03 and 1.58 in placebo groups (to Toxin A and B, respectively) |
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Henderson, M.; Bragg, A.; Fahim, G.; Shah, M.; Hermes-DeSantis, E.R. A Review of the Safety and Efficacy of Vaccines as Prophylaxis for Clostridium difficile Infections. Vaccines 2017, 5, 25. https://doi.org/10.3390/vaccines5030025
Henderson M, Bragg A, Fahim G, Shah M, Hermes-DeSantis ER. A Review of the Safety and Efficacy of Vaccines as Prophylaxis for Clostridium difficile Infections. Vaccines. 2017; 5(3):25. https://doi.org/10.3390/vaccines5030025
Chicago/Turabian StyleHenderson, Mackenzie, Amanda Bragg, Germin Fahim, Monica Shah, and Evelyn R. Hermes-DeSantis. 2017. "A Review of the Safety and Efficacy of Vaccines as Prophylaxis for Clostridium difficile Infections" Vaccines 5, no. 3: 25. https://doi.org/10.3390/vaccines5030025