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首页> 外文期刊>Antimicrobial agents and chemotherapy. >Fluoroquinolone resistance in Bacteroides fragilis following sparfloxacin exposure.
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Fluoroquinolone resistance in Bacteroides fragilis following sparfloxacin exposure.

机译:暴露于斯巴沙星后的脆弱拟杆菌中的氟喹诺酮耐药性。

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In vitro pharmacodynamic studies investigating the antimicrobial properties of five fluoroquinolones, (trovafloxacin, sparfloxacin, clinafloxacin, levofloxacin, and ciprofloxacin) against Bacteroides fragilis ATCC 23745 were conducted. The times required to reduce the viable counts by 3 log units were as follows: clinafloxacin, 2.9 h; levofloxacin, 4.6 h; trovafloxacin, 6 h; and sparfloxacin, 10 h. Exposure to ciprofloxacin did not achieve a 3-log decrease in viable counts. The susceptibility of B. fragilis was determined both prior to exposure and following 24 h of exposure to each of the five fluoroquinolones tested. The MICs of clinafloxacin, levofloxacin, trovafloxacin, sparfloxacin, ciprofloxacin, metronidazole, cefoxitin, chloramphenicol, and clindamycin were determined by the broth microdilution method. The MICs for B. fragilis preexposure were as follows: clinafloxacin, 0.25 &mgr;g/ml; trovafloxacin, 0.5 &mgr;g/ml; sparfloxacin, 2 microg /ml; levofloxacin, 2 microg/ml; and ciprofloxacin, 8 microg/ml. Similar pre- and postexposure MICs were obtained for cultures exposed to trovafloxacin, clinafloxacin, levofloxacin, and ciprofloxacin. However, following 24 h of exposure to sparfloxacin, a fluoroquinolone-resistant strain emerged. The MICs for this strain were as follows: clinafloxacin, 1 microg/ml; trovafloxacin, 4 microg/ml; sparfloxacin, 16 microg/ml; levofloxacin, 16 microg/ml; and ciprofloxacin, 32 microg/ml. No changes in the susceptibility of B. fragilis pre- and postexposure to sparfloxacin were noted for metronidazole (MIC, 1 microg/ml), cefoxitin (MIC, 4 microg /ml), chloramphenicol (MIC, 4 microg/ml), and clindamycin (MIC, 0.06 microg/ml). Resistance remained stable as the organism was passaged on antibiotic-free agar for 10 consecutive days. Mutant B. fragilis strains with decreased susceptibility to clinafloxacin, trovafloxacin, sparfloxacin, levofloxacin, and ciprofloxacin were selected on brucella blood agar containing 8x the MIC of levofloxacin at a frequencies of 6.4 x 10(-9), 4x the MICs of trovafloxacin and sparfloxacin at frequencies of 2.2 x 10(-9) and 3. 3 x 10(-10), respectively, and 2x the MIC of clinafloxacin at a frequency of 5.5 x 10(-11); no mutants were selected with ciprofloxacin. The susceptibilities of strains to trovafloxacin, levofloxacin, clinafloxacin, sparfloxacin, and ciprofloxacin before and after exposure to sparfloxacin were modestly affected by the presence of reserpine (20 microg/ml), an inhibitor of antibiotic efflux. The mechanism of fluoroquinolone resistance is being explored, but it is unlikely to be efflux due to a lack of cross-resistance to unrelated antimicrobial agents and to the fact that the MICs for strains before and after exposure to sparfloxacin are minimally affected by reserpine.
机译:进行了体外药效学研究,研究了五种氟喹诺酮类药物(曲伐沙星,司巴沙星,克林沙星,左氧氟沙星和环丙沙星)对脆弱拟杆菌的抗菌作用ATCC 23745。将存活计数减少3 log单位所需的时间如下:克林沙星2.9小时;左氧氟沙星,4.6小时;曲伐沙星,6 h;和司帕沙星,10 h。暴露于环丙沙星并没有使存活计数降低3-log。在暴露前和暴露于所测试的五种氟喹诺酮类药物中的每一种24小时后,都确定了脆弱的芽孢杆菌的敏感性。用肉汤微量稀释法测定克林沙星,左氧氟沙星,曲伐沙星,司巴沙星,环丙沙星,甲硝唑,头孢西丁,氯霉素和克林霉素的MIC。脆弱类芽孢杆菌预先暴露的MICs为:克林沙星,0.25 mg / ml;曲伐沙星,0.5 mg / ml;司帕沙星,2微克/毫升;左氧氟沙星,2微克/毫升;环丙沙星8微克/毫升。对于暴露于曲伐沙星,克林沙星,左氧氟沙星和环丙沙星的培养物,获得了相似的暴露前和暴露后MIC。但是,暴露于司帕沙星24小时后,出现了对氟喹诺酮耐药的菌株。该菌株的MICs如下:克林沙星,1 microg / ml;曲伐沙星,4微克/毫升;司帕沙星,16微克/毫升;左氧氟沙星,16微克/毫升;环丙沙星32微克/毫升。甲硝唑(MIC,1 microg / ml),头孢西丁(MIC,4 microg / ml),氯霉素(MIC,4 microg / ml)和克林霉素对脆性芽孢杆菌暴露前和暴露后对司帕沙星的敏感性没有变化(MIC,0.06微克/毫升)。当有机体连续10天在不含抗生素的琼脂上传代时,耐药性保持稳定。在布鲁氏菌血琼脂上选择对克林沙星,曲伐沙星,司巴沙星,左氧氟沙星和环丙沙星敏感度降低的脆弱B.突变菌株,其曲妥沙星的MIC为6.4x 10(-9)和oxoxfac为4x,而左氧氟沙星的MIC为8x。频率分别为2.2 x 10(-9)和3。3x 10(-10),是clinafloxacin MIC的2x,频率为5.5 x 10(-11);没有选择环丙沙星的突变体。利培平(20微克/毫升)(一种抗生素外排抑制剂)的存在会适度地影响菌株对曲伐沙星,左氧氟沙星,克林沙星,司帕沙星和环丙沙星的敏感性,而利血平(20微克/毫升)的存在会适度地影响菌株。氟喹诺酮耐药性的机制正在探索中,但由于对无关的抗微生物剂缺乏交叉耐药性,以及因暴露于司巴沙星前后的菌株的MIC对利血平的影响极小,因此不太可能外排。

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