Daily Trimethoprim-Sulfamethoxazole Prophylaxis Rapidly Induces Corresponding Resistance among Intestinal Escherichia Coli of HIV-infected Adults in Kenya.

Background. Trimethoprim-sulfamethoxazole (TMP-SMZ) has been recommended by World Health Organization (WHO) as daily prophylaxis for Africans with AIDS to prevent opportunistic infections. Daily TMP-SMZ may reduce its susceptibility to commensal intestinal Escherichia coli (E coli), increasing the burden of TMP-SMZ-resistant pathogens. Methods. Participants received either daily TMP-SMZ (CD4 <350 cells/mm3) or daily multivitamins (MVIs; CD4 ≥350 cells/mm3) for 6 months. Stool was collected at baseline, 2 weeks, 2 months, and 6 months. A random E coli was tested for susceptibility. Results. Baseline prevalence of TMP-SMZ resistance ranged from 71% to 81% and was not different across CD4 strata. At 2 weeks, prevalence of TMP-SMZ-resistant E coli increased significantly from 78% to 98% (P < .001) among persons taking daily TMP-SMZ and did not change among persons taking MVIs. Conclusions. Daily prophylaxis with TMP-SMZ induced in vivo resistance to the drug after 2 weeks. Empiric therapy for diarrhea with agents other than TMP-SMZ should be considered for HIV-infected persons receiving daily TMP-SMZ prophylaxis.