Venezia R A, Domaracki B E, Evans A M, Preston K E, Graffunder E M
Department of Pathology and Laboratory Medicine, Albany Medical Center, Albany, NY 12208, USA.
J Antimicrob Chemother. 2001 Sep;48(3):375-81. doi: 10.1093/jac/48.3.375.
To study the effect of fluoroquinolone exposure on the expression of mec(A)-encoded oxacillin resistance, population analysis profiling was performed on four strains of fluoroquinolone-susceptible, mec(A)-positive, heteroresistant Staphylococcus aureus. Growth in the presence of 0.5 x MIC of a fluoroquinolone resulted in >10-fold increase in the proportion of the population that grew on agar containing oxacillin 128 mg/L. Ciprofloxacin exhibited a greater effect than moxifloxacin, levofloxacin and gatifloxacin (average 3400-, 220-, 170- and 49-fold increase in oxacillin-resistant colonies versus the control, respectively). The increase was directly proportional to the fluoroquinolone concentration and could be detected as early as 8 h after exposure to the fluoroquinolone. At 8 h, the absolute number of colonies that grew on oxacillin 128 mg/L was similar whether or not the isolate was exposed to the fluoroquinolone, but the total cfu on non-selective media decreased. The resultant oxacillin-resistant colonies also showed a 1.5- to 3-fold increase in fluoroquinolone MIC. No oxacillin resistance was observed on two similarly treated fluoroquinolone-susceptible, mec(A)-negative strains. It appears that fluoroquinolones influence oxacillin resistance by selective inhibition or killing of the more susceptible subpopulations in heteroresistant S. aureus. The surviving populations are more resistant to both oxacillin and fluoroquinolone. The mechanisms of resistance to the two agents may be unrelated but tend to be associated. This could explain in part the observed increases in fluoroquinolone-resistant MRSA.
为研究氟喹诺酮类药物暴露对mec(A)编码的苯唑西林耐药性表达的影响，对四株氟喹诺酮敏感、mec(A)阳性、异质性耐药的金黄色葡萄球菌进行了群体分析谱研究。在含0.5倍氟喹诺酮最低抑菌浓度（MIC）的条件下生长，导致在含128mg/L苯唑西林的琼脂上生长的群体比例增加了10倍以上。环丙沙星的作用比莫西沙星、左氧氟沙星和加替沙星更大（与对照组相比，苯唑西林耐药菌落平均分别增加3400倍、220倍、170倍和49倍）。这种增加与氟喹诺酮浓度成正比，且在暴露于氟喹诺酮后最早8小时即可检测到。在8小时时，无论分离株是否暴露于氟喹诺酮，在128mg/L苯唑西林上生长的菌落绝对数相似，但非选择性培养基上的总菌落形成单位（cfu）减少。产生的苯唑西林耐药菌落的氟喹诺酮MIC也增加了1.5至3倍。在两株经过类似处理的氟喹诺酮敏感、mec(A)阴性菌株中未观察到苯唑西林耐药性。似乎氟喹诺酮类药物通过选择性抑制或杀灭异质性耐药金黄色葡萄球菌中更敏感的亚群来影响苯唑西林耐药性。存活的群体对苯唑西林和氟喹诺酮都更耐药。对这两种药物的耐药机制可能无关但往往相关。这可以部分解释所观察到的耐氟喹诺酮类的耐甲氧西林金黄色葡萄球菌（MRSA）的增加。
