Spam can not be stopped by hand. It is impossible. The average website with even a few users every day will receive as many as 300 spam comments every single day. It's not unheard of for a small business to receive thousands of spam emails and comments on their website every day. Spam is entirely automated - spam prevention must be automated too.
The best way to automate your spam prevention is with some kind of plugin or API. Services like Defendium help to stop spam using an API. Customers with legitimate websites can signup and send information to Defendium and Defendium will tell you whether or not the piece is spam.
Automated spam prevention tools take a look at the content of comments and analyze them against a database of thousands of other comments to determine if they are legitimate or not. They use sophisticated algorithms that look at various scoring factors to determine the likeliness of spam existing in a comment or not.
Some of the things an anti-spam API will look for are: