Gatifloxacinの細菌学的検討 In vitro antibacterial activity of gatifloxacin

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Gatifloxacin (GFLX) の各種臨床分離株に対するMIC<SUB>90</SUB>は, <I>Staphylococcus aureus</I> subsp. <I>aureus</I> (66株), メチシリン耐性<I>S.aureus</I> subsp.<I>aureus</I> (MRSA)(47株), 高度耐性MRSA (64株), coagulase-negative staphylococci (CNS)(41株), <I>Streptococcus pneumniae</I> (33株), ペニシリン低感受性<I>S.pneumniae</I> (17株), <I>Streptococcuspyogenes</I> (47株), <I>Entmcoccus faecalis</I> (37株), <I>Entmcoccus faecium</I> (41株), <I>Escherichia coli</I> (43株), <I>Klebsiella pmumoniae</I> subsp.<I>pneumoniae</I> (47株), <I>Proteusmimbilis</I> (48株), <I>Proteus vulgaris</I> (54株), <I>Mbrganella morganii</I> (49株), <I>Providmia rettgeri</I> (45株), <I>Sermtia mamscens</I> (50株), <I>Entmbacter cloacae</I> (50株), <I>Citrobacter freundii</I> (48株), <I>Acinetobacter</I> spp.(41株), <I>Pseudomnas aeruginosa</I> (32株), <I>Burkholderia cepacia</I> (33株), <I>Stenotrophomonas maltophilia</I> (47株), <I>Haemophilus influenzae</I> (54株), および<I>Bacteroides frogilis</I> (38株) に対して, それぞれ3.13, 0.2, 6.25, 0.2, 0.39, 0.39, 0.39, 0.78, 1.56, 0.39, 0.2, 0.39, 0.39, 0.78, 25, 1.56, 0.78, 1.56, 0.39, 6.25, 6.25, 0.78, ≦0.013および1.56μg/mLであった。<BR>GFLXはsparfloxacinと同等の幅広い抗菌スペクトルを有する新規のニューキノロン薬である。特にMRSAやペニシリン低感受性<I>S.pneumoniae</I>を含むグラム陽性菌に対しては, 他のニューキノロン薬に比べて優れた抗菌力を示した。<BR>Norfloxacin (NFLX) 耐性<I>S.aureus</I> subsp.<I>aureus</I>およびNFLX-ofloxacin (OFLX) 耐性<I>S.aureus</I> subsp.<I>aureus</I>のGFLXに対するMIC値を測定したところ, 本薬剤とNFLX, OFLXとの交差耐性は認められなかった。またキノロン感受性MRSAおよびNFLX-OFLX耐性MRSAの本薬剤に対する耐性変異率 (mutationrate) は低く, GFLXはブドウ球菌に対して耐性化を受けにくいニューキノロン薬と言えよう。<BR>GFLXのCHO-K1, HeLa, IMR-32細胞に対する細胞増殖抑制作用は50μg/mL以上の高濃度でOFLXより強く, OFLXよりは若干細胞毒性の強いニューキノロン薬であることが明らかになった。

The MIC values of the newly synthesized quinolone antibiotic gatifloxacin (GFLX)(Kyorin Pharmaceutical Co., Ltd., Tokyo) were determined with various bacterial species, and were compared with five other 4-quinolone antibiotics-ciprofloxacin, norfloxacin, ofloxacin, tosufloxacin, and sparfloxacin. MIC<SUB>90</SUB> values (μg/mL) of GFLX against various species or groups of bacteria (number of isolates in parentheses) were as follows: 3.13, <I>Staphylococcus aureus</I> subsp. <I>aureus</I> (66); 0.2, methicillinresistant <I>S. aureus</I> subsp. <I>aureus</I> (MRSA)(47, isolated in 1981); 6.25, MRSA (64, isolated in 1987); 0.2, coagulase-negative staphylococci (41); 0.39, <I>Streptococcus pneumoniae</I> (33); 0.39, penicillin-insensitive <I>S. pneumoniae</I> (17); 0.39, <I>Streptococcus pyogenes</I> (47); 0.78, <I>Enterococcus faecalis</I> (37); 1.56, <I>Enterococcus, faecium</I> (41); 0.39, <I>Escherichia coli</I> (43); 0.2, <I>Klebsiella pneumoniae</I> subsp. <I>pneumoniae</I> (47); 0.39, <I>Proteus mirabilis</I> (48); 0.39, <I>Proteus vulgaris</I> (54); 0.78, <I>Morganella morganii</I> (49); 25, <I>Providencia rettgeri</I> (47); 1.56, <I>Serratia marcescens</I> (50); 0.78, <I>Enterobacter cloacae</I> (50); 1.56, <I>Citrohacter freundii</I> (48); 0.39, <I>Acinetobacter</I> spp.(41); 6.25, <I>Pseudomonas aeruginosa</I> (32); 6.25, <I>Burkholderia cepacia</I> (33); 0.78, <I>Stenotrophomonas maltophilia</I> (47);≤0.013, <I>Haemophilus influenzae</I> (54); 1.56, <I>Bacteroides fragilis</I> (38). GFLX had an antibacterial spectrum similar to sparfloxacin, and had a better activity than the other 4-quinolones, especially against Gram-positive bacteria, including MRSA and penicillin-insensitive <I>S. pneumoniae. In vitro</I> activity against 30 MRSA strains isolated from 19 different countries during the period 1961 to 1986 was compared with that of five other 4-quinolones. MIC<SUB>90</SUB> of GFLX to MRSA from the various countries was 0.2μg/mL, 2-16-fold less than OFLX, NFLX, and CPFX, and 2-fold greater than SPFX and TFLX. To test the degree of cross-resistance to GFLX, we obtained isogenic sets of NFLX-resistant, and NFLX-OFLX resistant mutants from susceptible <I>S. aureus</I> strains. GFLX showed strong activity (MIC, 0.2μg/mL) against the NFLX-resistant mutants and also fairly good activity (MIC, 3.13μg/mL) against NFLX-OFLX-resistant mutants which harbored a mutation of the <I>gyrA</I> gene. Therefore, mutants resistant to NFLX and NFLX-OFLX showed incomplete cross-resistance to GFLX. GFLX selected the spontaneous resistant subclones from quinolone-susceptible and NFLX-OFLX-resistant MRSA at a low mutation rate. The selective toxicity of GFLX was determined by measuring growth inhibitory concentrations of this agent in cultured mammalian cells. At concentrations higher than 50μg/mL, GFLX manifested cytostatic activity to mammalian cells which was relatively stronger than that of OFLX.

収録刊行物

  • 日本化学療法学会雜誌 = Japanese journal of chemotherapy

    日本化学療法学会雜誌 = Japanese journal of chemotherapy 47, 48-56, 1999-09-27

    Japanese Society of Chemotherapy

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