In vitro combined effect of meropenem and various antimicrobial agents against beta-lactamase-nonproducing ampicillin-resistant Haemophilus influenzae and penicillin-resistant Streptococcus pneumoniae

摘要

As a basic study of combination therapy for bacterial meningitis, in vitro combined effect of meropenem (MEPM) and various antimicrobial agents against beta-lactamase-nonproducing ampicillin-resistant Haemophilus influenzae (BLNAR) and penicillin-resistant Streptococcus pneumoniae (PRSP) was investigated. The following findings were obtained. 1. In the checker board assay using 23 clinical isolates of BLNAR, MEPM+cefotaxime (CTX), MEPM+ampicillin (ABPC), and MEPM+rifampicin (RFP) showed synergistic effect (21 strains, 6 strains, 4 strains, respectively) or additive effect (2 strains, 17 strains, 19 strains, respectively). 2. In the checker board assay using 19 clinical isolates of PRSP, MEPM+CTX, MEPM+teicoplanin (TEIC), and MEPM+RFP showed synergistic effect (5 strains, 8 strains, 1 strain, respectively), additive effect (14 strains, 11 strains, 17 strains, respectively) or indifference (0 strain, 0 strain, 1 strain, respectively). 3. The time-kill assay with BLNAR demonstrated synergistic bactericidal effect of MEPM+CTX and MEPM+RFP, but not MEPM+ABPC. 4. The time-kill assay with PRSP demonstrated synergistic or additive bactericidal effect of MEPM+CTX, MEPM+TEIC, and MEPM+RFP. 5. There were no antagonistic effect in any combination tested in this study. These findings suggest that combination therapy with MEPM and various antimicrobial agents tested in this study are useful in treating bacterial meningitis caused by BLNAR and PRSP.