Extended Data Fig. 9: Darobactin single-dose pharmacokinetics and mouse thigh models.
From: A new antibiotic selectively kills Gram-negative pathogens
a, Three mice were intraperitoneally injected with 50 mg kg−1 darobactin, and blood samples were collected by tail snip over 24 h. Samples (n = 1 per time point and mouse) were analysed for darobactin content by LC–MS/MS, and concentrations were calculated using a standard curve created by linear regression on the log(area under the curve peak) to log(concentration) of standards. Pharmacokinetic values were calculated in Excel; t1/2 and time > MIC assuming first-order elimination and using linear regression on time points 3–8 h; AUC (0–16 h) using the trapezoid rule. The limit of detection (LOD) was 0.08 μg ml−1. b, A mouse thigh model was repeated three times testing the efficacy of darobactin against E. coli AR350. Mice were injected with bacteria in their right thigh at 0 h, then dosed with no drug, gentamicin or darobactin starting 2 h after infection (50 mg kg−1 once, 25 mg kg−1 given three times every 6 h, or 20 mg kg−1 once). At 26 h mice were euthanized and thighs collected and homogenized tissues were plated for c.f.u. analysis. Data are mean ± s.d.
