253 The sentence that begins Suggest replacing with general, the use of “In “recommended in vitro models…” assumes initially” with “may that in vitro and in vivo be used initially or models provide the same in conjunction with” answer. This can be to remove the especially challenging for suggestion of a novel antibacterial classes hierarchical where there is no historical approach to PK/PD basis for the PD profile or program design. the PK/PD driver of efficacy, when more robust growth can be achieved in vitro than in vivo, or in instances where in vitro resistance is greater than in vivo observations. 273 We that in vitro models Suggest adding do have some advantages in front of “may” over in vivo models, several “…have however these do not advantages…” to necessarily apply to all allow for alternate drugs. pathways for agents where good in vitro in vivo – correlations are not observed.
253 The sentence that begins with “In general, the use of in vitro models…” assumes that in vitro and in vivo models provide the same answer. This can be especially challenging for novel antibacterial classes where there is no historical basis for the PD profile or the PK/PD driver of efficacy, when more robust growth can be achieved in vitro than in vivo, or in instances where in vitro resistance is greater than in vivo observations. Suggest replacing “recommended initially” with “may be used initially or in conjunction with” to remove the suggestion of a hierarchical approach to PK/PD program design. 273 We that in vitro models do have some advantages over in vivo models, however these do not necessarily apply to all drugs. Suggest adding “may” in front of “…have several advantages…” to allow for alternate pathways for agents where good in vitro – in vivo correlations are not observed.