Gatifloxacinの細菌学的検討

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  • <I>In vitro</I> antibacterial activity of gatifloxacin

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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. MIC90 values (μg/mL) of GFLX against various species or groups of bacteria (number of isolates in parentheses) were as follows: 3.13, Staphylococcus aureus subsp. aureus (66); 0.2, methicillinresistant S. aureus subsp. aureus (MRSA)(47, isolated in 1981); 6.25, MRSA (64, isolated in 1987); 0.2, coagulase-negative staphylococci (41); 0.39, Streptococcus pneumoniae (33); 0.39, penicillin-insensitive S. pneumoniae (17); 0.39, Streptococcus pyogenes (47); 0.78, Enterococcus faecalis (37); 1.56, Enterococcus, faecium (41); 0.39, Escherichia coli (43); 0.2, Klebsiella pneumoniae subsp. pneumoniae (47); 0.39, Proteus mirabilis (48); 0.39, Proteus vulgaris (54); 0.78, Morganella morganii (49); 25, Providencia rettgeri (47); 1.56, Serratia marcescens (50); 0.78, Enterobacter cloacae (50); 1.56, Citrohacter freundii (48); 0.39, Acinetobacter spp.(41); 6.25, Pseudomonas aeruginosa (32); 6.25, Burkholderia cepacia (33); 0.78, Stenotrophomonas maltophilia (47);≤0.013, Haemophilus influenzae (54); 1.56, Bacteroides fragilis (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 S. pneumoniae. In vitro 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. MIC90 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 S. aureus 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 gyrA 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.

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