Guppy is a tier-A character since his starting item is quite powerfull and lets you snowball through the game with all the good cards. With the Infestation you loot 2 cards, but need to discard any card that you already have. That means that every turn you will end up drawing 2 cards, instead of 1.
You have more chances to obtain Soul of Gluttony, then the other characters.
A good time to use "Infestation" is when another player uses a card to manipulate the loot deck, using "Infestation" destroys the order of the cards being played.
Another good time to use it is having a card on this list.
- "XII The hanged man" Look at the top card of all decks, you may put those cards on the bottom of their decks, then loot 2
- "XVII The moon" Look at the top 5 cards of the loot deck, put 4 on the bottom of the deck and one back on top