rifabutin + trimethoprim sulfamethoxazole

This is a combination of three antibiotics—rifabutin, trimethoprim, and sulfamethoxazole—used together primarily for the treatment or prophylaxis of infections in immunocompromised patients, such as those with HIV. Rifabutin is a rifamycin antibiotic that inhibits bacterial DNA-dependent RNA polymerase, thereby suppressing RNA synthesis and subsequent protein production. Trimethoprim and sulfamethoxazole act synergistically to inhibit sequential steps in the bacterial folate synthesis pathway; sulfamethoxazole inhibits dihydropteroate synthase (blocking conversion of para-aminobenzoic acid to dihydropteroate), while trimethoprim inhibits dihydrofolate reductase (blocking reduction of dihydrofolic acid to tetrahydrofolic acid). This triple combination may be used when there is concern for resistant organisms or specific pathogens such as Mycobacterium avium complex (MAC) or Pneumocystis jirovecii pneumonia (PCP) in high-risk populations[1][3][4]. The combination can alter the metabolism and toxicity profile of its components; for example, rifabutin increases exposure to toxic metabolites of sulfamethoxazole[1].