Fig. 3: Prediction of linezolid clinical endpoints compared to observed clinical data.

In each panel simulation data from the translational tool and clinical observed data are shown in red and black, respectively. Shaded areas show 95 percentile intervals and solid lines represent means. Pharmacokinetic (PK) concentrations were simulated using a published population PK model⁵. A Prediction of monotherapy CFU decreases as compared to phase 2a trial data where mean CFU change and standard deviations are plotted¹⁷. The 600 QD group consisted of n = 10 patients, and the 600 BID group had n = 9 patients. B Simulation of Log₁₀ CFU over time and compared to Nix-TB collected TTP data that was converted to Log₁₀ CFU/mL^2,28. C Prediction of the probability of negative culture status over time on treatment compared to data from Nix-TB trial. Nix-TB trial predictions utilized individual-level data and included patient dosing history, baseline TTP, and individual PK parameters. D Prediction of the probability of negative culture status over time on treatment in ZeNix trial⁴. Predictions included patient-level baseline TTP data and Kaplan–Meier plots are separated by dose (1200 mg once daily vs 600 mg once daily) and the mean baseline TTP value of 13 days. E Lesion distribution using parameters estimated in rabbits². The selected monotherapy PD targets for LZD represented as dashed lines were MIC for uninvolved lung (0.5 mg/L), macrophage IC₉₀ for cellular lesions (6.25 mg/L), and caseum MBC90 for caseum (43 mg/L, outside y-axis range). Plasma is not considered a site of infection for tuberculosis and is therefore not included. CFU colony forming units, LZD linezolid, TTP time to positivity. Source data are provided as a Source Data file.