Yes, bacterial resistance to trimethoprim has been observed. Resistance mechanisms often involve mutations in the dihydrofolate reductase gene, which alter the enzyme's active site so that trimethoprim can no longer bind effectively. Understanding these resistance mechanisms can help in designing next-generation inhibitors that are less susceptible to such mutations. Additionally, combination therapies, such as co-administering trimethoprim with another antibiotic like sulfamethoxazole, are used to overcome resistance and enhance efficacy.
