Streptococcus pyogenes BM4478 and Staphylococcus aureus BM4479 were isolated from a patient undergoing rifampin therapy. High-level resistance to rifampin was due to the following mutations in the rpoB gene: Ser(552) Len in strain BM4478 and His(526)Asn and Ser(574)Leu in strain BM4479.