Sato S, Miura T, Kudo Y, Kudo E, Saitoh Y, Kimpara I, Tsujino M, Kudo H
School of Allied Medical Sciences, Hirosaki University.
Jpn J Antibiot. 1998 Jul;51(7):488-93.
The synergistic relationship between vancomycin (VCM) and carbapenem (CRB) has been reported in antibacterial activity against CRB-resistant strains of MRSA. The purpose of this study is to investigate the antibacterial activity against CRB-resistant MRSA using VCM, panipenem (PAPM), and a combination of both. 8 strains of CRB-resistant MRSA were used to examine the effects of these antibiotics by the broth microdiluton technique. The effect of pH (pH 6, 7, 8) on MIC of VCM alone was not observed in 7 out of 8 strains; MICs were between 1.0-2.0 micrograms/ml. PAPM alone, however, showed an enhancing tendency in alkaline condition in 6 out of 8 strains. There was no influence of pH on MICs in the combination use of VCM and PAPM, showing additive effect in 1 strain and synergistic in 6 strains. Killing-curves against PAPM-resistant MRSA were examined under the following drug combinations; 1/4 MIC of VCM (0.5 micrograms/ml) plus 1/4 MIC of PAPM (16 micrograms/ml), and 1/4 MIC of VCM plus 1/8 MIC of PAPM (8 micrograms/ml). The former drug combination showed synersistic effect; decrease from 1.05 x 10(5) to 6.45 x 10(4) CFU/ml after 6 hours' incubation and to less than 10 CFU/ml after 24 hours. The latter drug combination showed synergistic activity (2.68 x 10(2) CFU/ml) after 24 hours' incubation, but lost antibacterial activity after 48 hours. In conclusion, PAPM in combination with VCM showed synergistic effects on CRB-resistant MRSA. This combination therapy should be evaluated for the treatment of MRSA infection in patients with renal dysfunction.
