Effect of iptacopan (antifactor B), danicopan (antifactor D), eculizumab (anti-C5), ravulizumab (anti-C5), and AMY-101 (anti-C3) on complement-mediated killing (Nm and Hi) or whole blood killing (Sp). A twofold dilution series of complement inhibitors was made with pooled plasma. Gram-negative bacteria (Nm and Hi) were incubated in 10% plasma or heat-inactivated plasma for 30 minutes at 37°C, and survival was calculated by determining colony-forming units. For S pneumoniae, bacteria were added to washed blood cells and mixed with undiluted plasma or with undiluted heat-inactivated plasma and incubated for 1 hour at 37°C while shaking, and survival was calculated by determining colony-forming units. The percentage survival was normalized to heat-inactivated pooled plasma without inhibitors. Survival in pooled human plasma (mean ± standard error of the mean) is illustrated in red in each graph. The concentration effect curve on bacterial survival is presented in black (mean ± standard error of the mean is shown; Nm: n = 5 for AMY-101 and eculizumab, n = 4 for iptacopan, danicopan, and ravulizumab; Hi: n = 3 for ravulizumab, n = 5 for AMY-101, danicopan, and eculizumab, n = 6 for iptacopan; Sp: n = 4 for all inhibitors). IC50 values were determined using variable-slope, 4-parameter nonlinear regression analysis in GraphPad Prism.
