Unless you trust your users absolutely, you can't be 100% sure. Here are some suggestions though:
1. Use postfwd[1] to rate-limit the number of emails an account can send per day/hour/whatever. When spammers take over an account to send spam, they typically send a huge volume of spam in a short amount of time, which is hugely damaging to your reputation. Rate-limiting is an effective way to minimize the damage. The following postfwd rules should limit each SASL user to 50 messages per hour and 100 messages per day:
Code:
id=R001; sasl_username=~/./; action=rate(sasl_username/100/86400/REJECT only 100 messages per day for $$sasl_username)
id=R002; sasl_username=~/./; action=rate(sasl_username/50/3600/REJECT only 50 messages per hour for $$sasl_username)
2. Monitor the major blacklists for your IP address (you can do this yourself or use a free service such as mxtoolbox[2]), so you'll get alerted if your server is ever blacklisted. Then you'll know to look for a compromised account and apply for removal from blacklists. Policies vary between blacklist operators, but for the most part they're willing to de-blacklist you if you say you had a compromised account which you've taken care of. (I've administered email systems used by hundreds of users and this has happened to me a few times.)
Hope this helps.
[1]
http://postfwd.org/[2]
http://mxtoolbox.com/