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Cefepime 100 mg/kg q8h i.v. had minimal antimicrobial effect. When this background regimen of cefepime was combined with enmetazobactam half-maximal effect was induced with enmetazobactam 4.71 mg/kg q8h i.v. The dose fractionation study suggest both fTthreshold and fAUCMIC are potentially relevant PD indices. The AUCELFAUCplasma for cefepime and enmetazobactam was 73.4% and 61.5%, respectively. A ≥2-log kill in the lung was achieved with a plasma and ELF cefepime fTMIC of ≥20% and enmetazobactam fT2 mg/L of ≥20% of the dosing