Well the PYMX compounds kills bacteria in the same way that natural defensins do, but PYMX claim (with justification based on what I can tell) that their defensin mimics are both more potent and more selective (i.e. the concentration needed to kill bacteria vs. the concentration needed to damage human cells) than natural defensins.
The main point of the PPYMX drugs is they do not engender resistance - multiple passes of less-than-lethal concentration have no effect on MIC, unlike any other known antibiotic. The reason for this is that these molecules kill bacteria by physically damaging the bacteria cell wall - that's not something that a bacteria can easily mutate to avoid. The normal resistance mechanisms (efflux pumps etc.) simply never come into play.
So engendering resistance is not an issue here at all in my opinion. Safety and efficacy are the issues.
I admit I don't see the pathway towards resistance that you're clearly concerned about.
It's a partitioning mechanism into the lipid membrane, and i'm not sure outright how you develop a defense to that without the bacteria changing the composition of their walls?