This might be a little tough to answer but when was the Black Plague realised as more serious than an isolated outbreak, and how did people try and make themselves safer with ancient medical knowledge?

This is indeed a tough answer but I know that it was widely known in Europe that the Black Plague was a massive outbreak and not just an isolated incident. One of the ways used to protect from the disease was to quarantine and kill anyone who exhibited symptoms and their families as well. This practice was carried out in Milan in particular,

"In Milan, to take one of the most successful examples, city officials immediately walled up houses found to have the plague, isolating the healthy in them along with the sick. Venice took sophisticated and stringent quarantine and health measures, including isolating all incoming ships on a separate island. But people died anyway, though fewer in Milan and Venice than in cities that took no such measures"

One of my history professors in my medieval Europe class told me that it was well recorded that the Milanese authorities in particular would burn down the quarantined house with the occupants still alive inside to prevent any spread of the disease. Although pretty brutal these methods certainly kept Milan and Venice from having massive outbreaks like many other cities and countries of the time. In Poland King Casimir the Great also initiated quarantines on a massive scale, anyone wishing to enter Poland was kept under guard and each individual town and city was advised to be kept under quarantine as well. There was also a wide abundance of cats in Poland unlike other European countries of the time, which would eat the plague carrying rats. Although not exactly used as a mean to protect against the plague exclusively, Jews washed their hands as part of traditional religious practice, which in some areas protected them from getting infected by the plague. In the context of the question though, the last two answers I gave protected against the plague more by coincidence than design. I hope this at least partially answers your question!

Source for quote: http://www.militaryhistoryonline.com/general/articles/BlackDeath.aspx