Bezlotoxumab for prevention of Clostridium difficile infection recurrence: Distinguishing relapse from reinfection with whole genome sequencing. (February 2020)

• Record Type: Journal Article
• Authors: Zeng, Zhen; Zhao, Hailong; Dorr, Mary Beth; Shen, Judong; Wilcox, Mark H.; Poxton, Ian R.; Guris, Dalya; Li, Junhua; Shaw, Peter M.
• Is Part Of: Anaerobe. Volume 61(2020)
• Publication Date: 2020-02
• Subjects: Bezlotoxumab -- Clostridium difficile infection -- Recurrence -- Reinfection -- Relapse -- Single nucleotide polymorphism -- Whole genome sequencing; Anaerobic infections -- Periodicals; Anaerobic bacteria -- Periodicals; Bacterial diseases -- Periodicals; Computer network resources; Anaerobic protozoa -- Periodicals; 579.3
• DOI: 10.1016/j.anaerobe.2019.102137
• Languages: English
• ISSNs: 1075-9964

Abstract

Abstract: Background: Bezlotoxumab has been shown to prevent Clostridium difficile infection recurrence (rCDI) in high-risk patients. Methods: We used whole genome sequencing to estimate the impact of bezlotoxumab on same-strain relapse or new-strain reinfection in MODIFY I/II trials. Reinfection with a new strain and relapse with the same strain were differentiated by the comparison of ribotype (RT) and pair-wise single-nucleotide whole genome sequencing (WGS) variations (PWSNV). Relapse was assigned if the baseline RT and the RT isolated during rCDI were the same, and if PWSNVs were ≤ 2. Reinfection was assigned if the baseline RT and the RT isolated during rCDI were different, or if the RT was the same but PWSNVs were > 10. Unknown status was assigned if the RT was the same but PWSNVs were 3–10. Results: 259 rCDI events were evaluable (50 [19.3%] reinfection; 198 [76.4%] relapse). The proportion of relapses was higher for ribotype 027 (84.5%) compared with other ribotypes (74.1%). Cumulative incidence of relapse was significantly lower for bezlotoxumab versus no bezlotoxumab (p < 0.0001), with a non-significant trend towards reduction for reinfection (p = 0.14). Conclusion: Bezlotoxumab treatment significantly reduced the rate of CDI relapse versus a regimen without bezlotoxumab. (NCT01241552/NCT01513239). Highlights: More participants experienced relapse (50/259; 76%) vs reinfection (198/259; 19%). The proportion of relapses was higher for RT 027 vs all other RTs (84.5% vs 74.1%). A reduction in relapse incidence was seen in participants receiving bezlotoxumab.