Relationships among Ciprofloxacin, Gatifloxacin, Levofloxacin, and Norfloxacin MICs for Fluoroquinolone-Resistant Escherichia coli Clinical Isolates
Relationships among Ciprofloxacin, Gatifloxacin, Levofloxacin, and Norfloxacin MICs for Fluoroquinolone-Resistant Escherichia coli Clinical Isolates
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DOI：
10.1128/aac.00722-08
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发表时间：
2009-01-01
影响因子：
4.9
通讯作者：
Zechiedrich, Lynn
中科院分区：
文献类型：
--
作者：
Boyd, Lauren Becnel;Maynard, Merry J.;Zechiedrich, Lynn
氟喹诺酮类是美国处方量最大的一些抗生素。此前，我们及其他研究人员表明，就临床和实验室标准协会（CLSI）确定的耐药临界值而言，氟喹诺酮类呈现出一种类别效应，即对一种氟喹诺酮的敏感性降低（即最低抑菌浓度升高）意味着对所有氟喹诺酮的敏感性同时降低。然而，对于特定菌株，每种氟喹诺酮的药效学特性以及耐药相关基因型对每种氟喹诺酮最低抑菌浓度的影响程度存在明显差异。在对920株临床大肠杆菌分离株的一项初步研究中，我们发现诺氟沙星的最低抑菌浓度存在巨大差异。所有氟喹诺酮耐药分离株的最低抑菌浓度都超过了耐药临界值，达到1000微克/毫升。大约25%的分离株（n = 214），代表了耐药诺氟沙星最低抑菌浓度的整个范围，被选用于同时测定环丙沙星、加替沙星、左氧氟沙星和诺氟沙星的最低抑菌浓度。我们发现：（i）所有四种氟喹诺酮的最低抑菌浓度都存在很大差异；（ii）超过90%的氟喹诺酮耐药分离株的环丙沙星和左氧氟沙星最低抑菌浓度高于耐药临界值；（iii）环丙沙星和左氧氟沙星的最低抑菌浓度分布在两个不同的组中；（iv）两对药物（通过肯德尔Tau - b检验的环丙沙星和诺氟沙星以及通过配对t检验的加替沙星和左氧氟沙星）的最低抑菌浓度具有统计学意义上的相似性，但彼此不同；（v）约2%的分离株具有前所未有的氟喹诺酮最低抑菌浓度关系。因此，尽管就临床敏感性或耐药性而言，氟喹诺酮类可被视为等效，但对于氟喹诺酮耐药的临床分离株，氟喹诺酮的最低抑菌浓度差异显著，这可能是由于药物结构的差异。
Fluoroquinolones are some of the most prescribed antibiotics in the United States. Previously, we and others showed that the fluoroquinolones exhibit a class effect with regard to the CLSI-established breakpoints for resistance, such that decreased susceptibility (i. e., an increased MIC) to one fluoroquinolone means a simultaneously decreased susceptibility to all. For defined strains, however, clear differences exist in the pharmacodynamic properties of each fluoroquinolone and the extent to which resistance-associated genotypes affect the MICs of each fluoroquinolone. In a pilot study of 920 clinical Escherichia coli isolates, we uncovered tremendous variation in norfloxacin MICs. The MICs for all of the fluoroquinolone-resistant isolates exceeded the resistance breakpoint, reaching 1,000 mu g/ml. Approximately 25% of the isolates (n = 214), representing the full range of resistant norfloxacin MICs, were selected for the simultaneous determinations of ciprofloxacin, gatifloxacin, levofloxacin, and norfloxacin MICs. We found that (i) great MIC variation existed for all four fluoroquinolones, (ii) the ciprofloxacin and levofloxacin MICs of > 90% of the fluoroquinolone-resistant isolates were higher than the resistance breakpoints, (iii) ciprofloxacin and levofloxacin MICs were distributed into two distinct groups, (iv) the MICs of two drug pairs (ciprofloxacin and norfloxacin by Kendall's Tau-b test and gatifloxacin and levofloxacin by paired t test) were similar with statistical significance but were different from each other, and (v) similar to 2% of isolates had unprecedented fluoroquinolone MIC relationships. Thus, although the fluoroquinolones can be considered equivalent with regard to clinical susceptibility or resistance, fluoroquinolone MICs differ dramatically for fluoroquinolone-resistant clinical isolates, likely because of differences in drug structure.