Tankovic J, Bachoual R, Ouabdesselam S, Boudjadja A, Soussy C J
Service de Bactériologie-Virologie-Hygiène, Centre Hospitalier Universitaire Henri Mondor, Créteil, France.
J Antimicrob Chemother. 1999 May;43 Suppl B:19-23. doi: 10.1093/jac/43.suppl_2.19.
MICs of the new fluoroquinolone, moxifloxacin, and those of ciprofloxacin, ofloxacin and sparfloxacin for 19 genetically characterized fluoroquinolone-resistant strains were determined by the agar dilution method. The MICs of moxifloxacin for Escherichia isolates with one mutation in gyrA (corresponding to Ser83-->Leu or Asp87-->Gly substitution) were 0.25-0.5 mg/L, while those of ciprofloxacin, ofloxacin and sparfloxacin were 0.06-0.25, 1 and 0.12-0.5 mg/L, respectively. These values were four- to 16-fold higher than those of the same antibiotics for the wild-type strain, E. coli KL16. Similar results were observed with clinical isolates of Salmonella spp. harbouring one mutation in gyrA leading to the substitution of Ser83 by Phe or Tyr. In the presence of two mutations in the E. coli gyrA gene, the MICs of moxifloxacin ciprofloxacin, ofloxacin and sparfloxacin were 2, 0.5, 4 and 1 mg/L, respectively; these were 32 times higher than the MICs of these agents for E. coli KL16. The MICs of the four quinolones for triple mutants with two mutations in gyrA and one in parC were even higher, i.e. 8, 8, 16 and 8-16 mg/L, respectively. The MICs of moxifloxacin for Campylobacter coli and Campylobacter jejuni strains with a gyrA mutation leading to Thr86-->Ile substitution ranged from 1 to 2 mg/L, while the MICs of ciprofloxacin, ofloxacin and sparfloxacin were 16-32 mg/L, 8-16 and 4-8 mg/L, respectively. For high-level ciprofloxacin-resistant (MICs of 32 mg/L) clinical isolates of Enterococcus faecalis with one substitution at position 83 in GyrA (E. coli coordinates), the MICs of moxifloxacin, ofloxacin and sparfloxacin were 8-16, > or = 128 and 32 mg/L respectively. In conclusion, moxifloxacin and other fluoroquinolones exhibit cross-resistance against aerobic gram-negative bacilli and enterococci. The in-vitro activity of moxifloxacin was greater than that of ofloxacin and slightly less than that of ciprofloxacin and sparfloxacin against Enterobacteriaceae, but greater than those of the three other compounds tested against Campylobacter spp and E. faecalis.
采用琼脂稀释法测定了新型氟喹诺酮类药物莫西沙星以及环丙沙星、氧氟沙星和司帕沙星对19株经基因鉴定的耐氟喹诺酮菌株的最低抑菌浓度(MIC)。对于gyrA基因发生一个突变(对应于Ser83→Leu或Asp87→Gly替换)的大肠埃希菌分离株,莫西沙星的MIC为0.25 - 0.5mg/L,而环丙沙星、氧氟沙星和司帕沙星的MIC分别为0.06 - 0.25mg/L、1mg/L和0.12 - 0.5mg/L。这些值比野生型菌株大肠埃希菌KL16对相同抗生素的值高4至16倍。在gyrA基因发生一个导致Ser83被Phe或Tyr替换的突变的沙门氏菌临床分离株中也观察到了类似结果。在大肠埃希菌gyrA基因存在两个突变的情况下,莫西沙星、环丙沙星、氧氟沙星和司帕沙星的MIC分别为2mg/L、0.5mg/L、4mg/L和1mg/L;这些值比这些药物对大肠埃希菌KL16的MIC高32倍。对于gyrA基因有两个突变且parC有一个突变的三重突变体,这四种喹诺酮类药物的MIC甚至更高,分别为8mg/L、8mg/L、16mg/L和8 - 16mg/L。对于gyrA基因发生导致Thr86→Ile替换的突变的空肠弯曲菌和结肠弯曲菌菌株,莫西沙星的MIC范围为1至2mg/L,而环丙沙星、氧氟沙星和司帕沙星的MIC分别为16 - 32mg/L、8 - 16mg/L和4 - 8mg/L。对于在GyrA的83位(大肠埃希菌坐标)有一个替换的对环丙沙星高水平耐药(MIC为32mg/L)的粪肠球菌临床分离株,莫西沙星、氧氟沙星和司帕沙星的MIC分别为8 - 16mg/L、≥128mg/L和32mg/L。总之,莫西沙星和其他氟喹诺酮类药物对需氧革兰氏阴性杆菌和肠球菌表现出交叉耐药性。在体外,莫西沙星对肠杆菌科细菌的活性大于氧氟沙星,略低于环丙沙星和司帕沙星,但对弯曲菌属和粪肠球菌的活性大于其他三种受试化合物。