Ocular Surface and Inflammation Department, Ophthalmology, Hospital Clinico de San Carlos, Madrid, Spain.
Universidad Complutense, Madrid, Spain.
Clin Drug Investig. 2011;31(8):543-557. doi: 10.2165/11589020-000000000-00000.
This article discusses current practice in the treatment of conjunctivitis and how the use of topical moxifloxacin can increase therapeutic effectiveness, reduce treatment failures and, consequently, be cost effective and reduce the societal burden of the disorder. Current practice and effectiveness data were derived from the literature. Data on healthcare utilization as a result of treatment failure were collected by survey and the cost of treatment was defined using national costings. A decision-analytic model to assess cost effectiveness was developed and the impact on the healthcare budget was calculated to define the health economic impact. Bacterial conjunctivitis represents a significant health problem and accounts for an estimated 1-1.5% of primary-care consultations. The disorder is highly contagious and causes a substantial healthcare and societal burden. Bacterial conjunctivitis is generally self-limiting, resolving within 1-2 weeks. However, the use of antibacterials significantly improves clinical and microbiological remission, shortens symptom duration, and enables more effective use of healthcare resources, compared with placebo. From a health economic perspective this benefits the healthcare system and society, since fewer healthcare resources are needed and the adult affected, or the parent/caregiver of the child affected, can return to full work capacity sooner, reducing loss of productivity. Treatment strategies vary significantly between countries. Most patients are first seen in primary care, where 'wait-and-see', lubrification and antiseptic or antibacterial treatment is provided. In Europe, when antibacterials are prescribed most general practitioners (GPs) prescribe a broad-spectrum topical antibacterial. The most commonly used drugs are chloramphenicol and fusidic acid, with fluoroquinolones rarely reported as first-line treatment by GPs. At the specialist (ophthalmologist) level, or for second-line treatment at the GP level, topical antibacterials are frequently used. However, in most countries, topical fluoroquinolones, particularly those recently approved by the European Medicines Agency, such as topical levofloxacin and topical moxifloxacin, are rarely used and instead are reserved for use as a last resort. In other parts of the world topical lomefloxacin, gatifloxacin and/or besifloxacin are also available. The strategy of using novel topical fluoroquinolones as a last resort reflects a belief that the use of topical fluoroquinolones may enhance the development of resistance, jeopardizing future availability of antibacterial treatment for ocular infections. In fact, most cases of bacterial resistance arise as a result of systemic treatment. Thus, this concern should not be extrapolated to topical use of fluoroquinolones, which results in antibacterial concentrations at the ocular surface that can significantly exceed mutant prevention concentrations. In addition, with products such as topical moxifloxacin, a dual-step mutation is required for resistance to emerge. Moxifloxacin restricts the selection of resistant mutants, meaning that emergence of resistance is unlikely. The strategy of not using the most effective fluoroquinolones such as topical moxifloxacin may lead to more patients with no improvement or worsening of symptoms, requiring re-intervention, additional examination and new treatment; these outcomes are defined as 'treatment failures'. Treatment failures cause an extra societal burden and increased costs due to the extra healthcare resources required (additional GP/specialist visits, laboratory tests, additional treatment, etc.). Compared with non-fluoroquinolones, topical moxifloxacin has a higher potency and faster in vitro 'speed-to-kill'. It has also been shown that, within the fluoroquinolone class, topical moxifloxacin and besifloxacin achieve the highest mean concentrations in conjunctival tissue, have the longest residence times and display favourable area under the concentration-time curve from time zero to 24 hours (AUC(24))/minimum inhibitory concentration ratio required to inhibit the growth of 90% of organisms (MIC(90)) and thus favourable pharmacokinetic/pharmacodynamic characteristics. This can result in reduced time-to-cure and a lower number of treatment failures, leading to better disease management and a healthcare-economic benefit arising from the associated reduction in utilization of healthcare resources. The high potency and mean concentration in conjunctival tissue combined with the long residence time of topical moxifloxacin enables a dosing strategy of three times daily for 5 days. Topical moxifloxacin is also the first ophthalmic antibacterial in Europe provided as a multidose, self-preserved, topical solution, thus avoiding the risk of benzalkonium chloride preservative-related allergic reactions and swelling. In addition, topical moxifloxacin has a near neutral pH (6.8) and is well tolerated by patients. Given the characteristics of the novel topical fluoroquinolones, a change in the healthcare treatment strategy for acute infectious conjunctivitis is to be recommended. Topical application of fluoroquinolones, such as moxifloxacin multidose self-preserved solution, should be considered earlier in the treatment path for conjunctivitis. Notwithstanding the premium price attached to this novel topical antibacterial, use of topical moxifloxacin for bacterial conjunctivitis can be cost effective and even generate total healthcare budget savings by reducing both the costs of managing treatment failures and the use of clinicians' time to manage such failures.
本文讨论了结膜炎治疗的当前实践,以及局部莫西沙星的使用如何提高治疗效果,降低治疗失败率,从而具有成本效益,并减轻疾病对社会的负担。目前的实践和有效性数据来自文献。通过调查收集了因治疗失败而导致的医疗保健利用数据,并且使用国家成本数据来定义治疗费用。开发了一种评估成本效益的决策分析模型,并计算了对医疗保健预算的影响,以确定其对健康经济的影响。细菌性结膜炎是一个重大的健康问题,约占初级保健咨询的 1-1.5%。这种疾病具有很强的传染性,会对医疗保健和社会造成很大的负担。细菌性结膜炎通常是自限性的,在 1-2 周内即可痊愈。然而,与安慰剂相比,使用抗菌药物可以显著改善临床和微生物缓解,缩短症状持续时间,并更有效地利用医疗资源。从健康经济学的角度来看,这对医疗保健系统和社会都有益,因为需要的医疗资源减少,受影响的成年人或受影响儿童的父母/照顾者可以更快地恢复到满负荷工作状态,从而减少生产力损失。治疗策略在各国之间存在显著差异。大多数患者首先在初级保健机构就诊,在那里提供“观望”、润滑和防腐剂或抗菌治疗。在欧洲,当使用抗菌药物时,大多数全科医生(GP)会开广谱局部抗菌药物。最常用的药物是氯霉素和夫西地酸,很少有报告称氟喹诺酮类药物是 GP 的一线治疗药物。在专科(眼科医生)层面,或在 GP 层面的二线治疗中,经常使用局部抗菌药物。然而,在大多数国家,局部氟喹诺酮类药物,特别是最近被欧洲药品管理局批准的药物,如左氧氟沙星和莫西沙星,很少使用,而是留作最后手段。在世界其他地区,局部洛美沙星、加替沙星和/或贝西沙星也可使用。将新型局部氟喹诺酮类药物作为最后手段使用的策略反映了一种信念,即使用局部氟喹诺酮类药物可能会增强耐药性的发展,从而危及未来眼部感染的抗菌治疗。事实上,大多数细菌耐药性是由于全身治疗引起的。因此,这种担忧不应推断为局部使用氟喹诺酮类药物,因为局部使用氟喹诺酮类药物会导致眼部表面的抗菌浓度显著超过突变预防浓度。此外,对于莫西沙星等产品,需要双重突变才能出现耐药性。莫西沙星限制了耐药突变体的选择,这意味着耐药性不太可能出现。不使用最有效的氟喹诺酮类药物(如莫西沙星)的策略可能会导致更多患者症状没有改善或恶化,需要再次干预、额外检查和新的治疗;这些结果被定义为“治疗失败”。治疗失败会导致额外的社会负担和增加的成本,因为需要额外的医疗保健资源(额外的 GP/专科就诊、实验室检查、额外的治疗等)。与非氟喹诺酮类药物相比,局部莫西沙星具有更高的效力和更快的体外“杀菌速度”。研究还表明,在氟喹诺酮类药物中,局部莫西沙星和贝西沙星在结膜组织中达到最高的平均浓度,具有最长的停留时间,并显示出有利的 0 至 24 小时浓度时间曲线下面积/最小抑菌浓度比值(AUC(24))/最小抑菌浓度比值(MIC(90)),从而具有有利的药代动力学/药效动力学特征。这可以减少治愈时间和治疗失败的数量,从而更好地管理疾病,并通过减少对医疗资源的利用而带来医疗保健经济效益。局部莫西沙星的高效力和在结膜组织中的平均浓度与长停留时间相结合,使每天给药 3 次,持续 5 天的方案成为可能。局部莫西沙星也是欧洲第一种提供多剂量、自我保存的局部溶液的眼科抗菌药物,从而避免了苯扎氯铵防腐剂相关过敏反应和肿胀的风险。此外,局部莫西沙星的 pH 值接近中性(6.8),患者耐受性良好。鉴于新型局部氟喹诺酮类药物的特点,建议改变急性传染性结膜炎的医疗保健治疗策略。应更早地考虑在结膜炎的治疗路径中应用氟喹诺酮类药物,如莫西沙星多剂量自我保存溶液。尽管这种新型局部抗菌药物的价格较高,但使用莫西沙星治疗细菌性结膜炎具有成本效益,甚至可以通过减少治疗失败的管理成本和临床医生管理此类失败的时间来节省总医疗保健预算。