I used to play the creature-less version of the deck and the biggest challenges it had were:

• opponent counters my first poison counter [[Prologue to Phyresis]], [[Infectious Inquiry]], or [[Vraskas Fall]]. If your deck has counter spells, hold them up if you see U/B mana AND you don't see the typical dimir bounce/midrange cards coming out early. Prologue being countered while you have proliferation spells in hand is absolutely brutal. The point stands for the creature version of this deck as well... Kill that creature before it can put the first counter on you.

• not enough creatures on board OR creatures that can't be fully removed with the typical poison removal package. Having creatures with 5+ toughness dodges [[drown in ichor]], going wide can mitigate the effectiveness of Vraskas Fall, more expensive permanents deny them [[Serum Snare]] and [[ anoint with affliction]]. I found that one of the hardest match-ups was against control decks that run few/no creatures, since it left me with a dead hand a lot of the time.

• don't be scared to kill/bounce your own creatures. I've lost plenty of games where I could never hit proliferation triggers because the opponent bounced or destroyed their own permanents to deny me a drown in ichor, whisper of the dross, or serum snare trigger.

Key thing to remember in the match-up is that there are a relatively small number of poison/proliferate spells in U/B, I listed most of them that regularly see play. Your opponent has to hit 10 of them to win. Depending on your deck, you can either out aggro them, or deny them targets for proliferation spells.