This was very confusing to me when I started out. Your local friendly emergency room nurse will know the technicalities, but here are a few rules of thumb:
1. You should always obtain cultures prior to starting antibiotics.
2. Get 2 sets from 2 separate sites; don’t use a catheter at the time of insertion or a long-standing port.
3. To get 2 sets or 3 sets? The yield is about the same, but get 3 if contamination is suspected and pretest is low-moderate probability. If you get 2, you can get them at the same time, but the 3rd should be obtained 4-6 hrs later.