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尿路感染管理中的当前问题:缓释环丙沙星作为一种新型治疗选择。

Current issues in the management of urinary tract infections: extended-release ciprofloxacin as a novel treatment option.

作者信息

Blondeau Joseph M

机构信息

Royal University Hospital, University of Saskatchewan, 103 Hospital Drive, Saskatoon, Saskatchewan S7N 0W8, Canada.

出版信息

Drugs. 2004;64(6):611-28. doi: 10.2165/00003495-200464060-00004.

Abstract

Symptomatic urinary tract infections (UTIs) are a major public health concern in the developed world, accounting for almost 8 million annual outpatient and emergency department visits in the US alone, while also representing one of the most common hospital-acquired infections. The vast majority of uncomplicated UTIs are caused by the Gram-negative bacillus Escherichia coli, with other pathogens including enterococci, Staphylococcus saprophyticus, Klebsiella spp. and Proteus mirabilis. Effective management of UTIs in both the inpatient and outpatient settings has been complicated by the fact that many uropathogenic strains have developed resistance to antimicrobials, including cotrimoxazole (trimethoprim/sulfamethoxazole), the current first-line treatment for uncomplicated UTIs in the US and many other countries. In some countries, other antimicrobial therapies, such as trimethoprim and nitrofurantoin, are also used for treatment of uncomplicated UTIs. Antimicrobial resistance has been associated with an increased rate of clinical failure, and reports from Canada and the US indicate that the prevalence of cotrimoxazole resistance exceeds 15% and can be as high as 25%.The emergence and dissemination of antimicrobial resistance can be reduced with the use of agents that have favourable pharmacokinetic/pharmacodynamic profiles and convenient dose administration regimens that facilitate patient adherence and, therefore, pathogen eradication. Fluoroquinolones have been used successfully to treat a wide range of community- and hospital-acquired infections, and the rates of fluoroquinolone resistance have remained low. Use of fluoroquinolones is recommended for uncomplicated UTIs in areas where the incidence of cotrimoxazole resistance exceeds 10%, as well as for the treatment of complicated UTIs and acute pyelonephritis. Ciprofloxacin is a widely used fluoroquinolone with high bactericidal activity against uropathogens and well established clinical efficacy in the treatment of UTIs. A new, extended-release formulation of ciprofloxacin (Cipro XR) provides systemic drug exposure comparable with that achieved with twice-daily administration of conventional, immediate-release ciprofloxacin, while also attaining higher maximum plasma concentrations with less interpatient variability. Therapeutic drug concentrations with extended-release ciprofloxacin are established immediately after dose administration and maintained throughout the 24-hour dosage interval, permitting convenient, once-daily treatment. Clinical trial results confirm that extended-release ciprofloxacin is as safely used and effective as the conventional, immediate-release formulation of ciprofloxacin in patients with uncomplicated UTIs, complicated UTIs or acute uncomplicated pyelonephritis. These findings support the use of extended-release ciprofloxacin as a well tolerated, effective and convenient therapy for UTIs, which may improve patients' adherence to therapy and, thereby, reduce the risk of infection recurrence and emergence of antimicrobial resistance.

摘要

有症状的尿路感染(UTIs)是发达国家主要的公共卫生问题,仅在美国,每年就有近800万人次门诊和急诊就诊,同时也是最常见的医院获得性感染之一。绝大多数单纯性UTIs由革兰氏阴性杆菌大肠杆菌引起,其他病原体包括肠球菌、腐生葡萄球菌、克雷伯菌属和奇异变形杆菌。由于许多尿路致病菌株已对抗微生物药物产生耐药性,包括复方新诺明(甲氧苄啶/磺胺甲恶唑),这是美国和许多其他国家目前治疗单纯性UTIs的一线药物,因此在住院和门诊环境中有效管理UTIs变得复杂。在一些国家,其他抗菌疗法,如甲氧苄啶和呋喃妥因,也用于治疗单纯性UTIs。抗菌药物耐药性与临床治疗失败率增加有关,加拿大和美国的报告表明,复方新诺明耐药率超过15%,最高可达25%。使用具有良好药代动力学/药效学特征且剂量给药方案方便的药物,有助于患者依从性并从而根除病原体,可降低抗菌药物耐药性的出现和传播。氟喹诺酮类药物已成功用于治疗多种社区获得性和医院获得性感染,且氟喹诺酮类耐药率一直较低。在复方新诺明耐药率超过10%的地区,推荐使用氟喹诺酮类药物治疗单纯性UTIs,以及治疗复杂性UTIs和急性肾盂肾炎。环丙沙星是一种广泛使用的氟喹诺酮类药物,对尿路病原体具有高杀菌活性,在治疗UTIs方面具有公认的临床疗效。一种新的环丙沙星缓释制剂(Cipro XR)提供的全身药物暴露与每日两次服用传统速释环丙沙星相当,同时还能达到更高的最大血浆浓度,且患者间变异性较小。服用缓释环丙沙星后立即建立治疗药物浓度,并在整个24小时给药间隔内维持,允许方便的每日一次治疗。临床试验结果证实,在患有单纯性UTIs、复杂性UTIs或急性非复杂性肾盂肾炎的患者中,缓释环丙沙星的使用安全性和有效性与传统速释环丙沙星制剂相当。这些发现支持将缓释环丙沙星作为一种耐受性良好、有效且方便的UTIs治疗方法,这可能会提高患者对治疗的依从性,从而降低感染复发和抗菌药物耐药性出现的风险。

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