TY - JOUR

T1 - Bezlotoxumab for prevention of Clostridium difficile infection recurrence

T2 - Distinguishing relapse from reinfection with whole genome sequencing

AU - Zeng, Zhen

AU - Zhao, Hailong

AU - Dorr, Mary Beth

AU - Shen, Judong

AU - Wilcox, Mark H.

AU - Poxton, Ian R.

AU - Guris, Dalya

AU - Li, Junhua

AU - Shaw, Peter M.

PY - 2020

Y1 - 2020

N2 - 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).

AB - 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).

KW - Bezlotoxumab

KW - Clostridium difficile infection

KW - Recurrence

KW - Reinfection

KW - Relapse

KW - Single nucleotide polymorphism

KW - Whole genome sequencing

U2 - 10.1016/j.anaerobe.2019.102137

DO - 10.1016/j.anaerobe.2019.102137

M3 - Journal article

C2 - 31846705

AN - SCOPUS:85076467137

VL - 61

JO - Anaerobe

JF - Anaerobe

SN - 1075-9964

M1 - 102137

ER -