<p>KPC-producing Gram-negative pathogens have disseminated worldwide and cause infections of various organs and systems. Given the limited therapeutic options for such infections, trimethoprim-sulfamethoxazole may be a consideration. We evaluated the available in vitro and clinical data on trimethoprim-sulfamethoxazole for treating patients with infections caused by KPC-producing pathogens. Five resources (Embase, Google Scholar, Scopus, PubMed, and Web of Science) were used for identifying relevant studies. In total, 12 in vitro studies were included. These studies demonstrated that the susceptibility of KPC-producing pathogens to trimethoprim-sulfamethoxazole ranged from 7 to 100% (&gt; 70% in 7/12 studies), and the minimum inhibitory concentration (MIC) ranged from ≤ 0.25 (in 2 studies) to &gt; 32 (in 2 studies) mg/L. Additionally, a prospective cohort study evaluated 14 patients who received trimethoprim-sulfamethoxazole to treat infections caused by KPC-producing bacteria. Of those, 13 out of 14 (93%) patients achieved a clinical cure. Clinical published data assessing trimethoprim-sulfamethoxazole’s effectiveness for treating infections due to KPC-producing Gram-negative pathogens are limited. While data from in vitro studies suggest the consideration of trimethoprim-sulfamethoxazole when pathogens are susceptible, more clinical evidence is needed to use the drug safely in this population.</p>