We investigated the in vitro combination effect of teicoplanin (TEIC) and panipenem (PAPM) on highly oxacillin-resistant strains of Staphylococcus aureus (MRSA) isolated from various clinical specimens. Combination of TEIC and PAPM using checkerboard titration technique by agar dilution exhibited an excellent effect with mean fractional inhibitory concentration index of 0.18 +/- 0.07 on 47 MRSA strains, and the effects were judged as synergistic against all of the strains tested. In the combination of TEIC and PAPM at 1/4 MIC each against exponentially growing cells of MRSA, good bactericidal activity was found when TEIC and PAPM were added simultaneously, and PAPM was added at 1 or 2 hours prior to addition of TEIC, although the bactericidal activity was scarcely demonstrated when TEIC was added at 1 or 2 hours prior to addition of PAPM. Bactericidal activity against MRSA was enhanced in the combination of TEIC and PAPM at 1/4 MIC each for MRSA than the bactericidal activity of TEIC at 1 MIC alone. TEIC alone showed no bactericidal activity against P. aeruginosa in the mixed cultures with MRSA, while strong bactericidal activity against P. aeruginosa was induced by PAPM. In vitro bactericidal activities against mixed cultures of MRSA with P. aeruginosa were evaluated under conditions of concentrations of TEIC and PAPM, alone and in combination, whose plasma concentrations in human were simulated by a pharmacokinetic simulation model. Bactericidal activity against MRSA was enhanced by the combination of TEIC at 200 mg twice or once daily with PAPM at 500 mg twice daily in comparison with the bactericidal activity of each antibiotic alone, and P. aeruginosa was killed by the antibacterial activity of PAPM.