Schlech Barry A, Alfonso Eduardo
Alcon Research, Ltd., Fort Worth, Texas 76134-2099, USA.
Surv Ophthalmol. 2005 Nov;50 Suppl 1:S7-15. doi: 10.1016/j.survophthal.2005.05.002.
Antibiotics have been the mainstay of therapy for infectious diseases since their origins in the 1940s. As microorganisms changed and resistance developed, more advanced antibiotics were ultimately needed to provide adequate coverage and spectrum. By selecting optimal antibiotics and dosing regimens, clinicians can avoid treatment failures and adverse events and can help prevent the emergence of further antibiotic resistance. The fourth-generation ophthalmic fluoroquinolones include moxifloxacin (VIGAMOX, Alcon Laboratories, Inc., Fort Worth, TX) and gatifloxacin (Zymar, Allergan, Irvine, CA), and they are now approved for the treatment of bacterial conjunctivitis. This review highlights four scientific methods that compare and rank antibiotic potencies and predict their clinical efficacy and their propensity to develop resistance: 1) in vitro assay for minimum inhibitory concentrations, 2) in vivo models for pharmacokinetic and pharamacodynamic properties, 3) therapeutic index or inhibitory quotient, and 4) in vitro assay for mutant prevention concentration. The fourth-generation ophthalmic fluoroquinolones perform well in these assays. Both antibiotics have better in vitro activity against gram-positive bacteria than ciprofloxacin or ofloxacin. Moxifloxacin penetrates better into ocular tissues than gatifloxacin and older fluoroquinolones; in vitro activity of moxifloxacin and gatifloxacin against gram-negative bacteria is similar to that of older fluoroquinolones. Moxifloxacin also has better mutant prevention characteristics than other fluoroquinolones. These findings support the use of the newer fluoroquinolones for the prevention and treatment of serious ophthalmic infections (e.g., keratitis, endophthalmitis) caused by susceptible bacteria.
自20世纪40年代抗生素问世以来,一直是治疗传染病的主要手段。随着微生物的变化和耐药性的产生,最终需要更先进的抗生素来提供足够的覆盖范围和抗菌谱。通过选择最佳的抗生素和给药方案,临床医生可以避免治疗失败和不良事件,并有助于防止进一步的抗生素耐药性出现。第四代眼科氟喹诺酮类药物包括莫西沙星(VIGAMOX,爱尔康实验室公司,得克萨斯州沃思堡)和加替沙星(Zymar,爱力根公司,加利福尼亚州欧文),它们现已被批准用于治疗细菌性结膜炎。本综述重点介绍了四种比较和排序抗生素效力、预测其临床疗效和耐药性倾向的科学方法:1)最小抑菌浓度的体外测定;2)药代动力学和药效学特性的体内模型;3)治疗指数或抑制商;4)突变预防浓度的体外测定。第四代眼科氟喹诺酮类药物在这些测定中表现良好。这两种抗生素对革兰氏阳性菌的体外活性均优于环丙沙星或氧氟沙星。莫西沙星比加替沙星和 older fluoroquinolones 能更好地渗透到眼组织中;莫西沙星和加替沙星对革兰氏阴性菌的体外活性与 older fluoroquinolones 相似。莫西沙星的突变预防特性也优于其他氟喹诺酮类药物。这些发现支持使用新型氟喹诺酮类药物预防和治疗由易感细菌引起的严重眼部感染(如角膜炎、眼内炎)。