Abstract
Imipenem (IPM) and β-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 >100 μ9/ml and MICs of IPM and ABPC ranged from 12.5 to 100 μg/ml and from 12.5 to 50 μg/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 MUELLERHINTON broth against 5 fosfomycin (FOM)-resistant and 5 FOM-susceptible stains: (1) IPM 12.5 μg/ml,(2) ABPC 25 μg/ml,(3) IPM 12.5, μg/ml-FABPC 25 μg/ml,(4) IPM 6.25 μg/ml+ABPC25μg/ml,(5) IPM 6.25 μg/ml+ABPC 12.5 μg/ml,(6) IPM 6.25 μg/ml+ABPC 12.5 μg/ml+ FOM (fosfomycin) 25 μg/ml,(7) IPM 12.5 μg/ml+ ABPC 25 μg/ml+ FOM 50 μg/ml,(8) FOM 50 μgml.
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.
