Does Trimethoprim-Sulfamethoxazole Prophylaxis for HIV Induce Bacterial Resistance to Other Antibiotic Classes?: Results of a Systematic Review

Background. Trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis has long been recommended for immunosuppressed HIV-infected adults and children born to HIV-infected women. Despite this, many resource-limited countries have not implemented this recommendation, partly because of fear of widespread antimicrobial resistance not only to TMP-SMX, but also to other antibiotics. We aimed to determine whether TMP-SMX prophylaxis in HIV-infected and/or exposed individuals increases bacterial resistance to antibiotics other than TMP-SMX. Methods. A literature search was conducted in Medline, Global Health, Embase, Web of Science, ELDIS, and ID21. Results. A total of 501 studies were identified, and 17 met the inclusion criteria. Only 8 studies were of high quality, of which only 2 had been specifically designed to answer this question. Studies were classified as (1) studies in which all participants were infected and/or colonized and in which rates of bacterial resistance were compared between those taking or not taking TMP-SMX and (2) studies comparing those who had a resistant infection with those who were not infected. Type 1 studies showed weak evidence that TMP-SMX protects against resistance. Type 2 studies provided more convincing evidence that TMP-SMX protects against infection. Conclusion. There was some evidence that TMP-SMX prophylaxis protects against resistance to other antibiotics. However, more carefully designed studies are needed to answer the question conclusively.