Extended Data Fig. 2: In vitro and in vivo activity of ETX0462. | Nature

Extended Data Fig. 2: In vitro and in vivo activity of ETX0462.

From: Rational design of a new antibiotic class for drug-resistant infections

Extended Data Fig. 2

a, Percent cumulative growth inhibition of 40 MDR P. aeruginosa clinical isolates from the CDC MDR P. aeruginosa panel at increasing concentrations of ETX0462 (blue), meropenem-vaborbactam (MEM-VAB, red), imipenem-relebactam (IMI-REL, orange, ceftolozane-tazobactam (TOL-TAZ, purple) and ceftazidime-avibactam (CAZ-AVI, green). MICs were measured in singleton. b, A composite Emax fitting of the %fT>MIC vs change in CFU burden for 7 strains (MIC range of 0.25 − 4 mg/L, R2 = 0.87) evaluated in a murine neutropenic thigh model in vivo suggests > 1-log kill when unbound systemic concentrations of ETX0462 exceed the MIC for 60% of the dosing interval. c, Kaplan-Meier survival plot of Y. pestis CO92 infected mice using an aerosolized dose (20 X LD50 of 6.8 x 104 CFU) followed by treatment with ETX0462 vs. vehicle control, ciprofloxacin (CIP) or ceftazidime (CTZ) shows equivalent in vivo efficacy (Log-rank test p < 0.0001 vs. control).

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