Besifloxacin,a new ophthalmic fluoroquinolone for the treatment of bacterial conjunctivitis

Besifloxacin is a new fluoroquinolone anti-infective developed for ophthalmic use. Besifloxacin ophthalmic suspension 0.6% (Besivance?) was recently approved for the treatment of bacterial conjunctivitis. The objective of this article is to provide a comprehensive overview of microbiological, pharmacokinetic/pharmacodynamic and clinical studies with besifloxacin. Microbiological studies have demonstrated that besifloxacin has wide-spectrum and potent activity against common ocular pathogens, including Gram-negative and Gram-positive pathogens associated with bacterial conjunctivitis, and retained activity against fluoroquinolone-resistant staphylococci and multidrug-resistant strains. In preclinical and human studies, topically applied besifloxacin had a prolonged ocular concentration and minimal systemic exposure. In clinical studies, patients randomized to besifloxacin ophthalmic suspension 0.6% experienced significantly higher rates of clinical resolution and microbial eradication than patients randomized to vehicle. Besifloxacin ophthalmic suspension 0.6% was also found to be as effective and well tolerated as moxifloxacin ophthalmic solution 0.5%. The low minimum inhibitory concentrations and high attainment of pharmacodynamic targets with besifloxacin may contribute to a lower risk for the emergence of bacterial resistance, although further studies are needed. These data indicate that besifloxacin ophthalmic suspension 0.6% is an important new option for the treatment of bacterial conjunctivitis.     

7-[(1 S,4S )-3,3-二甲基-2-氧杂-5-氮杂二环[2.2.1]庚烷-5-基]-喹诺酮化合物的合成与抗菌作用

以（4R）－羟基－L脯氨酸为起始原料，经8步反应合成了[(1S,4S)-3，3－二甲基－2－氧杂－5－氮杂二环[2.2.1]庚烷，以此化合物作为喹诺酮类的7－位侧链，合成了3个衍生物，并测定了它们对10株革兰阳性菌和6株革兰阴性菌的MIC值。结果表明，它们的体外抗菌活性均低于对照药加替沙星和环丙沙星。     

我国西南地区2000年～2001年氟喹诺酮类药物用药分析

目的:调查分析2000年～2001年氟喹诺酮类药物在我国西南4省市医院中的用药情况,评估其现状和趋势。方法:对西南4省市共51家医院应用氟喹诺酮类药物的品种、用药金额、DDDs等进行统计分析。结果:2000年～2001年西南4省市51家医院共应用氟喹诺酮类药物10个品种;2000年与2001年的用药金额分别为74 208 227元和93 660 193元,年度增长26.21％,用药金额上升主要是左氧氟沙星、司帕沙星和依诺沙星的用量增加所致;2001年较2000年的DDDs减少17.58％,但平均DDD金额分别为21.54元和21.52元,无明显差异;两年中氧氟沙星、环丙沙星、诺氟沙星、洛美沙星滴眼液和滴鼻液用量较大。结论:氟喹诺酮类药物在西南地区是一类应用普遍的抗菌药物。一些较新的氟喹诺酮药物如左氧氟沙星和司帕沙星的用量增长迅速。     

In vitro and in vivo activities of sparfloxacin and reference drugs againstChlamydia pneumoniae

The activities of sparfloxacin and reference drugs againstChlamydia pneumoniae were compared by using in vitro and in vivo methods. The minimum inhibitory concentration (MIC) (μg/ml) ranges of sparfloxacin, levofloxacin, tosufloxacin, grepafloxacin, AM-1155, DU-6859a, clarithromycin, azithromycin, and minocycline for sixC. pneumoniae strains (two standard and four clinical strains) were 0.031 to 0.063, 0.25 to 0.5, 0.063 to 0.125, 0.063 to 0.125, 0.063 to 0.125, 0.031 to 0.063, 0.016 to 0.031, 0.125 to 0.25, and 0.016 to 0.031, respectively. The in vitro potency of sparfloxacin againstC. pneumoniae was similar to that of clarithromycin, minocycline, and DU-6859a, and higher than that of the other fluoroquinolones and azithromycin. Fatal pneumonia was induced in cyclophosphamide-treated leukopenic mice by intranasal inoculation withC. pneumoniae KKpn-2. Infiltration of the lung by neutrophils and lymphocytes was confirmed by histopathologic examination. Oral treatment with the various antichlamydial agents was given for seven days; sparfloxacin and minocycline had the lowest ED₅₀ (effective treatment dose in 50% of the mice; given as mg/kg per dose) (1.11 each), followed by DU-6859a (1.92), tosufloxacin (2.09), grepafloxacin (2.41), clarithromycin and azithromycin (2.48 each), AM-1155 (2.77), and levofloxacin (>10). These results suggest that sparfloxacin may be an effective agent forC. pneumoniae infection in humans.     

氟喹诺酮类药物所致急性间质性肾炎临床分析

目的:探讨氟喹诺酮类药物致急性间质性肾炎(AIN)的临床特点与治疗方法.方法:收集2002年1月至2010年9月在北京大学第一医院肾脏内科明确诊断为氟喹诺酮类药物所致AIN患者的临床资料进行回顾性分析.记录患者的一般情况、氟喹诺酮类药物应用情况、合并用药情况、实验室检查、肾脏病理学检查结果及随访情况.结果:共5例患者纳...     

氟喹诺酮类药物所致尖端扭转型室性心动过速

氟喹诺酮类常用药物中左氧氟沙星、环丙沙星、加替沙星和莫西沙星等可以引起尖端扭转型室性心动过速(TdP).TdP的临床表现为眩晕、昏厥甚至心搏停止,心电图可见QT间期延长及TdP.其发生机制尚不明确,可能与抑制心肌细胞K<'+>离子通道,使K<'+>外流受阻有关.氟喹诺酮类常用药物所致TdP的危险因素有女性、高龄、器质性心脏病(特别是充血性心力衰竭、QT间期延长、心动过缓)、肝肾功能损害、低钾低镁血症,以及合用可以引起QT间期延长的药物等.一旦患者出现QT间期延长及TdP应立即停药,补充钾和镁抑制早期后除极,也可采用人工临时心脏起搏或异丙肾上腺素提高基础心率.意识丧失和心室颤动者,可进行体外电复律.     

志贺菌耐喹诺酮类药物机制及研究进展

志贺菌是感染性腹泻最常见的病原菌之一,目前喹诺酮类药物是临床治疗细菌性痢疾的一线用药。但在抗生素的选择压力下,志贺菌对喹诺酮类药物耐药问题日渐严重,其耐药机制也越来越受到人们关注,尤其是近年来对质粒介导的喹诺酮耐药机制研究进展迅速。本文就近年来在志贺菌对喹诺酮类抗生素耐药机制研究中取得的新进展做一综述。     

2种氟喹诺酮类药物对临床分离金黄色葡萄球菌突变选择窗的影响

目的通过测定左氧氟沙星及莫西沙星对金黄色葡萄球菌临床分离菌株防突变浓度(MPC),比较氟喹诺酮类对金黄色葡萄球菌突变选择窗(MSW)的影响,为临床合理使用抗菌药物,防治细菌耐药产生提供依据。方法采用标准琼脂二倍稀释法测定2种氟喹诺酮药物对38株临床分离的金黄色葡萄球菌和金黄色葡萄球菌质控菌株ATCC25923的最低抑菌浓度(MIC),采用肉汤法富集3×1010CFU.mL-1的金黄色葡萄球菌测定2种氟喹诺酮药物MPC,计算MPC50、MPC90、MPC/MIC。结果左氧氟沙星对38株金黄色葡萄球菌的MPC90、MPC90/MIC90分别为16 mg.L-1、8,莫西沙星分别为2 mg.L-1、4;结合药物动力学参数莫西沙星400 mg.次-1,1次.d-1,其Cmax/MPC90、AUC/MPC90分别为2.3、18,左氧氟沙星500 mg.次-1的Cmax/MPC90、AUC/MPC90明显高于300 mg.d-1组,分别为0.5、2.4。结论对金黄色葡萄球菌的临床分离菌株莫西沙星比左氧氟沙星MPC90低,MSW窄,防突变能力更强。左氧氟沙星500 mg.次-1,1次.d-1,能够提高左氧氟沙星的防突变能力。     

Gram-negative prosthetic joint infection treated with debridement,prosthesis retention and antibiotic regimens including a fluoroquinolone

Information is required about treatment outcomes of Gram-negative prosthetic joint infections treated with prosthesis retention and surgical debridement, especially where biofilm-active antibiotics such as fluoroquinolones are used. The outcome of 17 consecutive patients with an early Gram-negative prosthetic joint infection who had been treated with prosthesis retention and surgical debridement was analysed. Enterobacteriaceae were isolated in 16 patients and infections were mixed with other organisms in 13 (76%) patients. The median joint age was 17 days and the median duration of symptoms before debridement was 7 days. All patients initially received intravenous β-lactam antibiotic therapy and 14 patients were then treated with oral ciprofloxacin. Treatment failure occurred in two patients over a median period of follow-up of 28 months. In only one patient was a relapsed Gram-negative infection responsible for the failure and this patient had not been treated with ciprofloxacin. The 2-year survival rate free of treatment failure was 94% (95% CI, 63–99%). Prosthesis retention with surgical debridement, in combination with antibiotic regimens including ciprofloxacin, was effective and should be considered for patients with early Gram-negative prosthetic joint infection.     

氟罗沙星的合成

以6，7，8－三氟－1，4－二氢－4－氧代－3－喹啉酸乙酯为原料，经氟乙基化、与N－甲基哌嗪缩合和水解等3步反应制得氟罗沙星，总收率67．5％。工艺操作简单，适于工业生产。