I personally also block access by web browsers to non-standard ports (aka not :80 or :443) via an app firewall (Little Snitch here). In this case it would have warned me when the compromised script would have called home to that endpoint on the non-standard port.

Gotta tackle such issues at different places all at once for sure. It's like wearing 5 digital condoms at once. Too bad there's still some leakage somewhere for sure. B)

DNS level is more secure but less effective because apps and website can serve the essential content on the same domain as the advertisement. It will also become less effective over time.

YouTube does this, so you need to use a browser-based ad blocker.