Fusahiro Higashitani

Synthesis and antibacterial activity of 7-hydrazinoquinolones

A series of new C-7 substituted hydrazino quinolones and naphthyridines were prepared and tested for antibacterial activity. The hydrazine bridge at the C-7 position did not favor the antibacterial activity, whereas the nature of other substituents at N-1, C-5 and C-8 did noticeably influence the antibacterial activity. The 7-(1-aminomorpholino) derivatives exhibited superior antibacterial activity against Gram-positive and inferior activity against Gram-negative bacteria than the 7-(1-aminopiperazinyl) derivatives. Substitution of the quinolone at position-1 with cyclopropyl was the most beneficial for antibacterial activity among the series of compounds prepared.

Superior Effect of Tazobactam/ Piperacillin Compared to Piperacillin on β-Lactamase-Producing Pseudomonas aeruginosa

To evaluate the synergistic antimicrobial effects of tazobactam (TAZ), a beta-lactamase inhibitor, and piperacillin (PIPC) on Pseudomonas aeruginosa, we compared the antimicrobial effects of TAZ/PIPC with those of PIPC alone on bacteria inducibly or constitutively producing beta-lactamase. TAZ/PIPC had more potent antimicrobial effects compared with PIPC on clinical isolates producing beta-lactamase. In the treatment of mouse systemic infection, the therapeutic effect of PIPC was markedly decreased by beta-lactamase, but that of TAZ/PIPC was only slightly decreased. In the treatment of local infections in mice, the therapeutic effects of PIPC were decreased due to the induction of beta-lactamase and the emergence of bacterial strains constitutively producing beta-lactamase, while those of TAZ/ PIPC were not affected.