TY - JOUR
T1 - Renal impairment, C. difficile recurrence, and the differential effect of bezlotoxumab
T2 - A post hoc analysis of pooled data from 2 randomized clinical trials
AU - Golan, Yoav
AU - DuPont, Herbert L.
AU - Aldomiro, Fernando
AU - Jensen, Erin H.
AU - Hanson, Mary E.
AU - Dorr, Mary Beth
N1 - Publisher Copyright:
© The Author(s) 2020.
PY - 2020/7/1
Y1 - 2020/7/1
N2 - Background. Renal impairment is not a consistently cited risk factor for recurrent Clostridioides difficile infection (rCDI). We examined the association between renal impairment and rCDI and the effect of bezlotoxumab, an anti-toxin B monoclonal antibody, in reducing rCDI in participants with renal impairment. Methods. We pooled data from 2 randomized, double-blind, placebo-controlled, multicenter, phase 3 clinical trials conducted in participants receiving bezlotoxumab or placebo infusion during oral antibacterial drug treatment for CDI. We assessed the association between renal impairment and rCDI in placebo-treated participants and evaluated the effect of bezlotoxumab vs placebo in reducing rCDI among participants with renal impairment, defined as an estimated glomerular filtration rate <90 mL/min. Results. The proportion of placebo-treated participants experiencing rCDI within 12 weeks was higher in those with renal impairment (n = 919) vs those without renal impairment (n = 612; 36.6% and 27.7%, respectively; difference, 8.9%; 95% CI, 1.3% to 16.3%). Renal impairment was significantly associated with a higher rate of recurrence in placebo-treated participants lacking commonly recognized risk factors for rCDI (renal impairment as only risk factor, 28.8%; vs normal renal function and no risk factors, 12.5%; difference, 16.3%; 95% CI, 3.4% to 28.8%). Among all participants with renal impairment, the rate of rCDI was 19.5% among bezlotoxumab-treated vs 36.6% among placebo-treated participants (difference, -17.1%; 95% CI, -23.4% to -10.6%). Conclusions. This post hoc analysis adds to the literature suggesting an association of renal impairment as an independent risk factor for rCDI and provides preliminary evidence that patients with renal impairment who suffer with CDI may benefit from adjunctive treatment with bezlotoxumab.
AB - Background. Renal impairment is not a consistently cited risk factor for recurrent Clostridioides difficile infection (rCDI). We examined the association between renal impairment and rCDI and the effect of bezlotoxumab, an anti-toxin B monoclonal antibody, in reducing rCDI in participants with renal impairment. Methods. We pooled data from 2 randomized, double-blind, placebo-controlled, multicenter, phase 3 clinical trials conducted in participants receiving bezlotoxumab or placebo infusion during oral antibacterial drug treatment for CDI. We assessed the association between renal impairment and rCDI in placebo-treated participants and evaluated the effect of bezlotoxumab vs placebo in reducing rCDI among participants with renal impairment, defined as an estimated glomerular filtration rate <90 mL/min. Results. The proportion of placebo-treated participants experiencing rCDI within 12 weeks was higher in those with renal impairment (n = 919) vs those without renal impairment (n = 612; 36.6% and 27.7%, respectively; difference, 8.9%; 95% CI, 1.3% to 16.3%). Renal impairment was significantly associated with a higher rate of recurrence in placebo-treated participants lacking commonly recognized risk factors for rCDI (renal impairment as only risk factor, 28.8%; vs normal renal function and no risk factors, 12.5%; difference, 16.3%; 95% CI, 3.4% to 28.8%). Among all participants with renal impairment, the rate of rCDI was 19.5% among bezlotoxumab-treated vs 36.6% among placebo-treated participants (difference, -17.1%; 95% CI, -23.4% to -10.6%). Conclusions. This post hoc analysis adds to the literature suggesting an association of renal impairment as an independent risk factor for rCDI and provides preliminary evidence that patients with renal impairment who suffer with CDI may benefit from adjunctive treatment with bezlotoxumab.
KW - Bezlotoxumab
KW - Clostridioides difficile
KW - Recurrence
KW - Renal dysfunction
UR - http://www.scopus.com/inward/record.url?scp=85090775202&partnerID=8YFLogxK
U2 - 10.1093/ofid/ofaa248
DO - 10.1093/ofid/ofaa248
M3 - Article
AN - SCOPUS:85090775202
SN - 2328-8957
VL - 7
JO - Open Forum Infectious Diseases
JF - Open Forum Infectious Diseases
IS - 7
M1 - ofaa248
ER -