She left him for a Fungus Demon. It's all he talks about some days...
Harmony Kendall to Buffy Summers on Drusilla and Spike's breakup[src]

Fungus demons were a species of demon. In 1999, after a short reconciliation, Drusilla possibly cheated on Spike with a member of this species. However, no other mention of a fungus demon is made for the remainder of the series. Drusilla is shown cheating on Spike with a Chaos Demon in Fool For Love so it may be that Harmony misappropriated the name.