Bezlotoxumab for prevention of Clostridium difficile infection recurrence: Distinguishing relapse from reinfection with whole genome sequencing
Zhen Zeng, Hailong Zhao, Mary Beth Dorr, Judong Shen, Mark H Wilcox, Ian R Poxton, Dalya Guris, Junhua Li, Peter M Shaw, Zhen Zeng, Hailong Zhao, Mary Beth Dorr, Judong Shen, Mark H Wilcox, Ian R Poxton, Dalya Guris, Junhua Li, Peter M Shaw
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).
Keywords: Bezlotoxumab; Clostridium difficile infection; Recurrence; Reinfection; Relapse; Single nucleotide polymorphism; Whole genome sequencing.
Conflict of interest statement
Declaration of competing interest ZZ, MBD, JS, DG, and PMS are employees of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, and may own stock and/or stock options in the company. MHW has received consulting fees from Actelion, Astellas, bioMerieux, Cambimune, Da Volterra, MedImmune, Menarini, MSD, Meridian, Pfizer Inc., Qiagen, Sanofi-Pasteur, Seres, Summit, Synthetic Biologics, Inc., and Valneva; lecture fees from Alere, Astellas, MSD, and Pfizer Inc.; and grant support from Actelion, Astellas, bioMerieux, Da Volterra, MSD, Sanofi-Pasteur, Seres, and Summit. HZ and JL are employees of BGI-Shenzhen, Shenzhen, China. IRP has received consulting fees from Astellas and a research grant from ViroPharma.
Copyright © 2020 Merck Sharp & Dohme Corp. and The Author(s). Published by Elsevier Ltd.. All rights reserved.
Source: PubMed