Hooper David C
Division of Infectious Diseases, Infection Control Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114-2696, USA.
Lancet Infect Dis. 2002 Sep;2(9):530-8. doi: 10.1016/s1473-3099(02)00369-9.
Resistance to fluoroquinolones among Gram-positive cocci has emerged as these antimicrobial agents have become extensively used in clinical medicine. Resistance is effected by changes in the bacterial target enzymes DNA gyrase and topoisomerase IV, which reduce drug binding, and by action of native bacterial membrane pumps that remove drug from the cell. In both cases, quinolone exposure selects for spontaneous mutants that are present in large bacterial populations, and which contain chromosomal mutations that alter the target protein or increase the level of pump expression. Resistance among clinical isolates has been greatest in Staphylococcus aureus and particularly among meticillin-resistant strains, in which both selection by quinolone exposure and transmission of clonal strains in health-care settings have contributed to high prevalence. Resistance in Streptococcus pneumoniae has also emerged in the community. Fluoroquinolone resistance has arisen in multidrug-resistant clones and its prevalence has been especially high in Hong Kong and Spain. Further spread and selection of such resistance could compromise the utility of a valuable class of antimicrobial agents, a point that emphasises the importance of the careful use of these agents in appropriate patients and doses, as well as careful infection-control practices.
随着氟喹诺酮类抗菌药物在临床医学中广泛应用，革兰氏阳性球菌对其的耐药性问题逐渐显现。耐药性的产生是由于细菌靶酶DNA回旋酶和拓扑异构酶IV发生变化，减少了药物结合，以及细菌天然膜泵的作用将药物从细胞中清除。在这两种情况下，喹诺酮类药物的暴露会选择出存在于大量细菌群体中的自发突变体，这些突变体含有改变靶蛋白或增加泵表达水平的染色体突变。临床分离株中的耐药性在金黄色葡萄球菌中最为严重，尤其是在耐甲氧西林菌株中，喹诺酮类药物暴露的选择作用以及医疗环境中克隆菌株的传播都导致了高流行率。肺炎链球菌的耐药性在社区中也已出现。氟喹诺酮类耐药性出现在多重耐药克隆中，在香港和西班牙其流行率尤其高。这种耐药性的进一步传播和选择可能会损害这一重要类别的抗菌药物的效用；这一点强调了在适当的患者中以适当剂量谨慎使用这些药物以及严格执行感染控制措施的重要性。
