Supplementation Likely Helpful
Both trimethoprim and sulfamethoxazole interfere with folate: The sulfamethoxazole makes it hard for invading bacteria to manufacture folate, and the trimethoprim makes it hard for bacteria to use the folate. The net effect is to starve the bacteria of this necessary vitamin.
Humans and other mammals are much less affected by these antibiotics than are bacteria, due to the different way we process folate. However, trimethoprim can still interfere to some extent in your body's ability to utilize this essential nutrient. Folate supplementation may be helpful if you take this antibiotic for a long period of time (to prevent urinary tract infections, for example).