BACKGROUND: Penicillin- and multidrug-resistant Streptococcus pneumoniae became a global problem during recent decades. Multidrug resistance poses a serious threat to clinical medicine due to restriction of selecting appropriate antimicrobial agents to treat with. Current data suggest that any single antimicrobial agent cannot be a satisfactory option to treat pneumococcal infections caused by multidrug-resistant strains, particularly in meningitis. The aim of the study was to assess in vitro efficacy of several antimicrobial combinations that are commonly used in clinical practice, and to obtain reasonable candidate regimens that can be applied to in vivo model. METHODS: We performed time-kill studies of antimicrobial combinations including penicillin, cefotaxime, vancomycin, gentamicin, imipenem and ampicillin against five multidrug-resistant strains and two penicillin-susceptible strains. Penicillin, cefotaxime and vancomycin were combined with gentamicin, respectively. Cefotaxime plus vancomycin, imipenem plus vancomycin, and cefotaxime plus ampicillin combinations were also tested. Synergy was defined as a >or =100-fold or 2-log decrease in colony count at 24 h by the combination compared with that by the most active single agent. RESULTS: Penicillin plus gentamicin, cefotaxime plus gentamicin, and vancomycin plus cefotaxime combinations were demonstrated to have in vitro synergistic activities against multidrug-resistant strains. CONCLUSION: Three combinations showed in vitro synergism against penicillin- resistant pneumococci. Experimental animal study is warranted to determine the clinical relevance of the in vitro results.