Antibacterial activity of imipenem in combination with ampicillin against methicillin-resistant strains of Staphylococcus aureus

Imipenem (IPM) and beta-lactams have been reported to possess a synergistic relationship in their activities against methicillin (DMPPC)-resistant strains of Staphylococcus aureus (MRSA). The purpose of this study was to determine activities of IPM and ampicillin (ABPC) singly and in combination against MRSA. Activities of the 2 antibiotics against 19 strains of S. aureus resistant to DMPPC were investigated by means of the checkerboard method, the disk diffusion technique and the killing-curve method. MICs of DMPPC against these strains determined using the agar dilution method were greater than or equal to 100 micrograms/ml and MICs of IPM and ABPC ranged from 12.5 to 100 micrograms/ml and from 12.5 to 50 micrograms/ml, respectively, when used singly. The following results were obtained with the checkerboard method: Synergistic effects and additive effects were found against 13/19 and against 6/19 strains, respectively, and no antagonistic effect was found according to the FIC (fractionary inhibitory concentration) index. The disk diffusion technique indicated synergistic results. Killing-curves with the following drug concentration combinations were examined in Mueller-Hinton broth against 5 fosfomycin(FOM)-resistant and 5 FOM-susceptible stains: (1) IPM 12.5 micrograms/ml, (2) ABPC 25 micrograms/ml, (3) IPM 12.5 micrograms/ml + ABPC 25 micrograms/ml, (4) IPM 6.25 micrograms/ml + ABPC 25 micrograms/ml, (5) IPM 6.25 micrograms/ml + ABPC 12.5 micrograms/ml, (6) IPM 6.25 micrograms/ml + ABPC 12.5 micrograms/ml + FOM (fosfomycin) 25 micrograms/ml, (7) IPM 12.5 micrograms/ml + ABPC 25 micrograms/ml + FOM 50 micrograms/ml, (8) FOM 50 micrograms/ml. The following results were obtained with the killing-curve method; (1) Synergistic effects were found against 8/10 strains and no antagonistic effect was found with the combinations of IPM and ABPC. (2) Synergistic effects were found against 3/5 strains and no antagonistic effect was found with the combinations of IPM, ABPC and FOM against 5 FOM-susceptible strains. Conclusions: IPM in combination with ABPC produced synergistic effects against MRSA. This combination therapy should be evaluated in treating MRSA infections.