Department of Internal Medicine, Rush University Medical Center , Chicago, Illinois, USA.
J Ocul Pharmacol Ther. 2012 Feb;28(1):3-11. doi: 10.1089/jop.2011.0072. Epub 2011 Oct 14.
To determine the most appropriate methods for assessing the potential effectiveness of the newer topical fluoroquinolones gatifloxacin, moxifloxacin, and besifloxacin.
This article is based on a literature search for published articles about the pharmacokinetic (PK) and pharmacodynamic (PD) characteristics of and measure of bacterial susceptibility to topical ophthalmic fluoroquinolones. Search terms included fluoroquinolones, susceptibility, resistance, minimal/minimum inhibitory concentration (MIC), PDs, PKs, and ocular, ophthalmic, or topical antibiotics.
Topical fluoroquinolones, particularly besifloxacin, gatifloxacin, and moxifloxacin, have become important treatment options for common ocular bacterial infections due to their broad-spectrum bactericidal activity and low toxicity. An important challenge in ophthalmology is identifying the most accurate in vivo and in vitro methods for evaluating the efficacy of these topical fluoroquinolones. The MIC is the most commonly used measure of in vitro susceptibility. In systemic therapy, this measure is combined with PK data of antibiotics to generate PD indices PK/PD whose breakpoints differentiate clinically susceptible from nonsusceptible bacterial pathogen populations. PD breakpoints are further tested in prospective studies for their ability to predict clinical efficacy. However, it is not known whether systemically derived breakpoints apply to the assessment of clinical susceptibility to ocular agents. Topical ocular antibiotics likely achieve higher concentrations at the target site than do systemically administered antibiotics, but these higher concentrations can be quickly reduced by reflex tearing and blinking induced by instillation. Hence, studies have been conducted in animals and humans to determine the PK concentrations of topically administered antibiotics in ocular compartments. When combined with MIC values for topical pathogens, the results have the potential to predict clinical efficacy after identification of the appropriate PK/PD target. Ocular studies incorporating PK/PD assessments have recently begun to be reported with newer fluoroquinolones, including besifloxacin, gatifloxacin, and moxifloxacin, whose prolonged contact time and potent bactericidal activity have translated into some of the most favorable PK/PD target values. However, the clinical relevance of these studies has yet to be determined.
There is still a clear need for predictive models to extend our understanding of the clinical susceptibility of ocular pathogens.
确定评估新型局部氟喹诺酮类药物加替沙星、莫西沙星和贝西沙星潜在有效性的最合适方法。
本文基于对已发表的有关局部眼科氟喹诺酮类药物药代动力学（PK）和药效学（PD）特征以及细菌对局部眼用氟喹诺酮类药物敏感性的测量的文献检索。检索词包括氟喹诺酮类、敏感性、耐药性、最小/最小抑菌浓度（MIC）、PDs、PKs 以及眼部、眼科或局部抗生素。
由于局部氟喹诺酮类药物（尤其是贝西沙星、加替沙星和莫西沙星）具有广谱杀菌活性和低毒性，因此已成为治疗常见眼部细菌感染的重要选择。眼科的一个重要挑战是确定评估这些局部氟喹诺酮类药物疗效的最准确的体内和体外方法。MIC 是最常用的体外敏感性测量方法。在全身治疗中，该测量方法与抗生素的 PK 数据相结合，生成 PD 指数 PK/PD，其断点将临床敏感与非敏感的细菌病原体群区分开来。PD 断点在前瞻性研究中进一步测试其预测临床疗效的能力。然而，尚不清楚系统衍生的断点是否适用于评估眼部药物的临床敏感性。局部眼用抗生素在靶部位可能达到比全身给予的抗生素更高的浓度，但这些更高的浓度可以通过滴眼时引起的反射性流泪和眨眼迅速降低。因此，已经在动物和人类中进行了研究，以确定局部给予的抗生素在眼部隔室中的 PK 浓度。当与局部病原体的 MIC 值结合使用时，这些结果有可能在确定适当的 PK/PD 目标后预测临床疗效。最近开始报告包含 PK/PD 评估的眼科研究，包括贝西沙星、加替沙星和莫西沙星，它们的长接触时间和强大的杀菌活性转化为一些最有利的 PK/PD 目标值。然而，这些研究的临床相关性尚未确定。
仍然需要预测模型来扩展我们对眼部病原体临床敏感性的理解。
