Blondeau J M
Department of Clinical Microbiology, Saskatoon District Health and St. Paul's Hospital (Grey Nuns'), Saskatchewan, Canada.
Clin Ther. 1999 Jan;21(1):3-40; discussion 1-2. doi: 10.1016/s0149-2918(00)88266-1.
In general, the fluoroquinolones developed over the past few years have greater potency, a broader spectrum of antimicrobial activity, greater in vitro efficacy against resistant organisms, and a better safety profile than other antimicrobial agents, including the older quinolones. The present review focuses on 4 new quinolones that are commercially available (levofloxacin, trovafloxacin, grepafloxacin, and sparfloxacin) and 3 that are currently undergoing clinical trials (gatifloxacin, moxifloxacin, and clinafloxacin). Examination of the minimum inhibitory concentrations of these drugs against gram-positive, gram-negative, anaerobic, and atypical organisms demonstrates their increased potency in vitro. The available clinical evidence, although sparse, suggests the potential enhanced efficacy of these drugs in the treatment of various community-acquired and nosocomial infections (eg, respiratory, urinary tract, and skin infections and sexually transmitted diseases). Compared with ciprofloxacin, their pharmacokinetic profiles demonstrate equivalent or greater bioavailability, higher plasma concentrations, and increased tissue penetration, as reflected in greater volume of distribution. Adverse events seen with most quinolones are mild. Serious adverse effects that may occur are phototoxicity (particularly with sparfloxacin) and prolongation of the QTc interval (seen with sparfloxacin and grepafloxacin). Drug interactions are possible between multivalent cation-containing compounds and all quinolones and between theophylline and both ciprofloxacin and grepafloxacin. Drugs that prolong the QTc interval should not be coadministered with sparfloxacin and grepafloxacin. Step-down therapy, a therapeutic and cost-saving advantage possible with gatifloxacin, levofloxacin, and moxifloxacin, allows the switching of patients from intravenous to oral therapy without having to change the dosage regimen or class of antibiotics. In addition to shortening the hospital stay and reducing the risk of venous complications, step-down therapy has been shown to cut hospital drug costs by 40% and hospitalization costs by 20%.
总体而言,过去几年研发的氟喹诺酮类药物比其他抗菌药物(包括老一代喹诺酮类)具有更强的效力、更广泛的抗菌活性谱、对耐药菌更强的体外疗效以及更好的安全性。本综述聚焦于4种已上市的新型喹诺酮类药物(左氧氟沙星、曲伐沙星、格帕沙星和司帕沙星)以及3种正在进行临床试验的药物(加替沙星、莫西沙星和克林沙星)。对这些药物针对革兰氏阳性菌、革兰氏阴性菌、厌氧菌和非典型菌的最低抑菌浓度进行检测,证明了它们在体外具有更强的效力。现有临床证据虽然稀少,但表明这些药物在治疗各种社区获得性和医院感染(如呼吸道、泌尿道和皮肤感染以及性传播疾病)方面可能具有更高的疗效。与环丙沙星相比,它们的药代动力学特征显示出相当或更高的生物利用度、更高的血浆浓度以及更强的组织穿透力,这体现在分布容积更大。大多数喹诺酮类药物出现的不良事件较为轻微。可能发生的严重不良反应包括光毒性(尤其是司帕沙星)和QTc间期延长(司帕沙星和格帕沙星可见)。含多价阳离子的化合物与所有喹诺酮类药物之间以及茶碱与环丙沙星和格帕沙星之间都可能发生药物相互作用。延长QTc间期的药物不应与司帕沙星和格帕沙星联合使用。加替沙星、左氧氟沙星和莫西沙星具有治疗和节省成本的优势,即降阶梯疗法,可使患者从静脉治疗转换为口服治疗,而无需改变给药方案或抗生素类别。除了缩短住院时间和降低静脉并发症风险外,降阶梯疗法已被证明可使医院药品成本降低40%,住院成本降低20%。