Streptococcus pneumoniae isolates with varying degrees of resistance to penicillin have been described. Strains that are highly resistant to penicillin (MIC, > 1-mu-g/mL) and that are resistant to multiple antibiotics have been reported primarily in South Africa and Spain. We report a case of an adult patient with bacteremia due to S. pneumoniae that was highly resistant to penicillin (MIC, 4-mu-g/mL) and resistant to erythromycin, clindamycin, chloramphenicol, and co-trimoxazole who was successfully treated with vancomycin.