Grepafloxacinの in vitro, in vivo 抗菌作用  [in Japanese] In vitro and in vivo antibacterial activity of grepafloxacin  [in Japanese]

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Abstract

ニューキノロン薬grepafloxacin (GPFX) の<I>in vitro</I>および<I>in vivo</I>抗菌力について検討し.以下の結果を得た。<BR>1. GPFXは好気性菌及び嫌気性菌に対し幅広い抗菌スペクトラムと強い抗菌力を有していた。<BR>2. 臨床分離菌株に対するGPFXの抗菌力は, グラム陽性菌では比較薬剤中最も強い抗菌力を示し, グラム陰性菌ではCPFXに次ぐ抗菌力であった。<BR>3. GPFXは各種測定培地, 培地のpH, 接種菌量, 血清添加および金属イオンの影響をほとんど受けなかったが, 培地の酸性pHおよび高濃度の金属イオン存在下で, わずかに抗菌力の低下が認められた。<BR>4. GPFXはMIC以上の濃度で用量依存的に殺菌作用を示し, MICとMBCの差は小さく, 殺菌的に作用した。<BR>5. GPFXに対する自然耐性菌の出現頻度は低く, 継代培養による耐性も獲得しにくかった。<BR>6. GPFXは<I>Escherichia coli</I>由来のDNA gyraseにより, DNAから超螺旋型DNA生成する反応を強く阻害した。<BR>7. GPFXのpost antibiotic effect (PAE) は<I>Staphylococcus aureus</I> FDA 209Pで2時間, <I>E. coli</I> NIHJ JC-2 で1.6時間であり, CPFX同様に比較的長かった。<BR>8. マウス実験的感染症に対するGPFXの治療効果は, グラム陽性菌では比較薬剤のなかで最も強く, グラム陰性菌ではCPFXと同等もしくは優れた効果を示した。<BR>以上の<I>in vitro</I>および<I>in vivo</I>抗菌作用の検討成績より, GPFXは呼吸器感染症をはじめ各種細菌感染症に対して, 有用な薬剤であることが示唆された。

The <I>in vitro</I> and <I>in vivo</I> antibacterial activities of grepafloxacin (GPFX), a new synthetic antimicrobial agent, were compared with those of norfloxacin (NFLX), ofloxacin (OFLX), enoxacin (ENX) and ciprofloxacin (CPFX). GPFX showed a broad spectrum of antibacterial activity against gram-positive and gram-negative and aerobic and anaerobic bacteria. GPFX was superior to reference compounds in activity against all gram-positive clinical isolates, including <I>Staphylococcus aureus</I> and <I>Streptococcus pneumoniae</I>. The antibacterial activity of GPFX against <I>Escherichia coli, Citrobacter diversus, Klebsiella pneumoniae</I> and <I>Enterobacter aerogenes</I> was similar to that of CPFX and superior to those of NFLX, ENX and OFLX. The activity of GPFX against <I>Klebsiella oxytoca, Enterobacter cloacae, Serratia marcescens, Pseudomonas aeruginosa</I> and <I>Pseudomonas putida</I> was slightly less than that of CPFX but more active than those other reference drugs. The activity was similar to that of ENX against <I>Citrobacter freundii, Proteus vulgaris, Proteus mirabilis, Providencia rettgeri</I> and <I>Morganella morganii</I>. GPFX was superior to the reference compounds in activity against <I>Haemophilus influenzae, Xanthomonas maltophilia, Acinetobacter calcoaceticus, Moraxella (Branhamella) catarrhalis</I> and <I>Bacteroides fragilis</I>. Neither the medium, variation in medium pH, inoculum size, nor the addition of cations or horse serum had any major effect on its activity. But the activity of GPFX was slightly reduced in the acidic condition and of a high concentration of cations. GPFX acted bactericidally over the MIC, and differences were very small between the MIC and MBC.<BR>Frequencies of mutants resistant to GPFX were low. GPFX strongly inhibited the supercoiling activity of DNA gyrase purified from <I>E. coli</I> K-12. But inhibition of the relaxing activity of topoisomerase II from calf thymus was very low. GPFX produced excellent postantibiotic effects (PAE) against <I>S. aureus</I> and <I>E. coli</I>, and those effects were 2 and 1.6 hours, respectively. The therapeutic effect of these quinolones was evaluated against systemic infections in mice. GPFX was the most active against all the gram-positive bacterial infections. In gram-negative bacterial infections, GPFX was similar in activity to CPFX against <I>E. coli</I> and <I>P. aeruginosa</I> infections and was most active against <I>H. influenzae</I> infection. These results indicate that GPFX may be useful for various kinds of infections in humans.

Journal

  • Japanese Journal of Chemotherapy

    Japanese Journal of Chemotherapy 43, 74-90, 1995-07-31

    Japanese Society of Chemotherapy

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