Most highly informed people (as in, survived attacks by knives and been in countless street fights) I've spoken to highly recommend Kali and its various offshoots for knife defense
I train with a pretty brutal shotokan dojo and we do, in fact, mix a lot of escrima (kali) into our stuff.
but we focus on severing the bicep, slashing/stabbing the neck and belly, and generally hurting the attacker very, very badly. there really isnt a safe way to defend against a knife, its mostly an issue of counter-attacking.
for that matter you dont even need a knife to counter attack.
If you are thinking about "knife defense" chances are you have already been stabbed, or soon will be. now its just an issue of bloodying the guy before he bloodies you, which can be done with your fist/boot.