Streptococcus pneumoniae serotype 3, isolated from a penicillin-allergic patient and initially susceptible to fluoroquinolones, macrolides, lincosamides, quinupristin-dalfopristin, and telithromycin, became resistant to all these drugs during treatment. Mutations in the parC and gyrA and in the 23S rRNA and the ribosomal protein L22 genes were detected in the resistant isolates.