A case of rhabdomyolysis with fatal outcome after a treatment with levofloxacin

Fluoroquinolones are known to cause rhabdomyolysis. Levofloxacin is a recent fluoroquinolone and its muscular toxicity is not well documented. We describe the case of a 77-year-old female patient, who presented with an acute rhabdomyolysis after treatment with levofloxacin. She had a background of serious cardio-pulmonary disease. She received an oral ambulatory treatment with levofloxacin for pulmonary infection. After 6 days, she presented with severe rhabdomyolysis, resulting in complete anuria with hyperkalaemia, complicated with acute liver cytolysis and respiratory failure. The treatment was a daily repeated haemodialysis. She presented with a fatal myocardial infarction 13 days after admission. The medical history inclines us to strongly suspect levofloxacin as the cause of this severe adverse drug reaction. We also reviewed 27 other suspect cases reported in the database provided by the World Health Organization Collaborating Centre for Drug Monitoring (Uppsala, Sweden). We conclude that rhabdomyolysis can be a rare, severe adverse effect of levofloxacin, as well as the other fluoroquinolones.     

阿奇霉素与左氧氟沙星门诊治疗慢性支气管炎急性发作的对照研究

目的比较口服阿奇霉素与左氧氟沙星门诊治疗慢性支气管炎轻-中度急性发作的疗效和安全性。方法采用随机、开放、对照方法分为两组,共入选慢性支气管炎轻-中度急性发作门诊就诊者65例,阿奇霉素组32例(实际完成治疗30例),口服阿奇霉素500mg,1次/d,连续5d;左氧氟沙星组33例(实际完成治疗32例),口服左氧氟沙星500mg,1次/d,连续7d。结果治疗后第10天、第24天两组疗效比较差异无统计学意义(P>0.05)。两组临床症状改善所需时间、平均症状严重程度评分比较差异均无统计学意义(P>0.05)。两组细菌清除率、非典型病原体感染率间差异均无统计学意义(P>0.05)。两组不良反应发生率均较低,且差异无统计学意义(P>0.05)。结论口服阿奇霉素5d与口服左氧氟沙星7d门诊治疗慢性支气管炎轻-中度急性加重均有效且安全。     

顺序注射分光光度法测定左氧氟沙星、氧氟沙星和洛美沙星

本文基于左氧氟沙星、氧氟沙星和洛美沙星分别与Fe(Ⅲ)作用形成黄色络合物的现象,建立了简单、快速测定药物中左氧氟沙星、氧氟沙星和洛美沙星的顺序注射分光光度新方法。讨论了物理因素和化学因素对方法灵敏度的影响。测定左氧氟沙星、氧氟沙星和洛美沙星的工作曲线的线性范围均为10~250μg/ml。采用摩尔比法和连续变换法测定络合物的组成,Fe(Ⅲ)与药物的组成比为1∶2。将方法用于药物中左氧氟沙星、氧氟沙星和洛美沙星的测定,并与参考方法进行了对照。     

乳酸左氧氟沙星乳膏的制备与质量控制

目的:制备左旋氧氟沙星乳膏,建立质量控制方法。方法:以左旋氧氟沙星为主药,10%硬脂酸、4.6%单硬脂酸甘油脂、0.46%对羟基苯甲酸乙酯、1%甘油,2%十八醇、12%凡士林、2%三乙醇胺组成O/W型乳膏,制备左旋氧氟沙星乳膏。用荧光分光光度计在325nm处用共振瑞利散射法测定左旋氧氟沙星的含量,建立质量控制方法。结果:其线性范围为1～15.2mg/L,平均回收率为100.14%,RSD为1.93%。结论:制备方法和质量控制方法简便、快捷、准确。     

甲磺酸左氧氟沙星血、尿浓度测定及人体内的药代动力学

采用反相高效液相色谱法测定口服甲磺酸左氧氟沙星后人血清及尿中左旋氧氟沙星药物浓度,色谱柱为ＡＬＬＴＩＭＡＣ１８５μｍ,２５０ｍｍ×４．６ｍｍ。流动相为０．００５ｍｏｌ／Ｌ磷酸溴化四丁基铵乙腈（１１１）,ｐＨ＝２．８,流速１．５ｍｌ／ｍｉｎ,荧光检测激发波长２９８ｎｍ,发射波长４５８ｎｍ,以环丙沙星为内标,室温下血、尿样品用１０％三氯乙酸沉淀蛋白后,取上清液进样测定。此方法日内、日间误差均小于６％,平均血清回收率为９４．５２％,尿回收率为９８．６８％。最低检测浓度为２ｎｇ／ｍｌ。应用此方法研究了１６名健康男性志愿者分两组分别单剂口服１００或２００ｍｇ国产甲磺酸左氧氟沙星片的药代动力学。试验结果表明,甲磺酸左氧氟沙星片在健康志愿者体内表现为明显的线性药动学,血药浓度数据符合二室模型,大部分药物以原型从尿中排泄。本项研究结果为国产甲磺酸左氧氟沙星片的临床应用提供了科学依据。     

甲磺酸左氧氟沙星口服和皮下给药对小鼠腹腔感染的保护作用

金葡球菌、大肠埃希氏菌和铜绿假单胞菌各２株分别给小鼠腹腔感染,甲磺酸左氧氟沙星口服或皮下给药,以评价其体内保护作用。甲磺酸左氧氟沙星对２株金葡球菌感染小鼠的口服给药ＥＤ５０分别为７．４和６．２８ｍｇ／ｋｇ;对２株大肠埃希氏菌感染小鼠的ＥＤ５０分别为０．３７和１．１９ｍｇ／ｋｇ;对２株铜绿假单胞菌感染的ＥＤ５０分别为１９．７４和２３．７５ｍｇ／ｋｇ。３种细菌对小鼠感染的口服给药保护效果与左氧氟沙星碱相似,而优于氧氟沙星。甲磺酸左氧氟沙星对３种细菌小鼠感染的皮下给药的保护效果比口服给药优越２～１３倍。小鼠感染皮下给药条件下,甲磺酸左氧氟沙星对３种细菌感染的效果与左氧氟沙星相似,比氧氟沙星效果优４倍。     

甲磺酸左氧氟沙星的药代动力学研究

用微生物法测定了ＭＳＡＬＶＬＸ在狗体内的药代动力学过程符合二室模型。４、８和１６ｍｇ／ｋｇ口服给药的Ｃｍａｘ分别为１．７３、２．８９和８．２８ｍｇ／Ｌ,ＡＵＣ值分别为１５．４３、３１．９５和７０．２ｍｇｈ／Ｌ,ＭＲＴ分别为６．９６、７．５８和６６２８ｈ。大鼠口服２０ｍｇ／ｋｇ的Ｃｍａｘ为２．８６ｍｇ／Ｌ,ｔ１／２β为２．２ｈ,ＡＵＣ为７．４ｍｇｈ／Ｌ,ＭＲＴ为３ｈ。大鼠口服后７２ｈ的尿中排泄率为４２％,而７２ｈ胆汁排泄率为３８．２％。     

Randomized, double-blind study comparing 5- and 7-day regimens of oral levofloxacin in patients with acute exacerbation of chronic bronchitis

A randomized, double-blind, multicentre study was conducted in adult patients with acute exacerbation of chronic bronchitis (AECB), to compare the efficacy of a 5-day course of levofloxacin 500 mg once daily, with the standard 7-day regimen at the same dose. Five hundred and thirty-two patients from 48 centres in 10 countries were randomized to receive levofloxacin: 268 and 264 received the 5- and 7-day courses, respectively. The primary efficacy analysis was the clinical response at 7–10 days post-treatment in the per-protocol (PP) population. Clinical success rates in the primary PP analysis of 482 patients were 82.8% (197/238) for the 5-day group and 84.8% (207/244) for the 7-day group. The difference in success rates was −2.1% with a 95% CI of (−9.1 to 4.9%). The bacteriological response showed eradication rates of 82.1% (92/112) and 83.2% (84/101) in the 5- and 7-day groups, respectively. Both treatments were well tolerated. These results show that for patients with AECB levofloxacin 500 mg once daily for 5 days provides equivalent clinical and bacteriological success to the same dose given for 7 days irrespective of the patient's age, the frequency of exacerbations or the presence of co-existing cardiopulmonary or chronic obstructive airways disease.     

喹诺酮类药物在妇幼保健医院的应用进展

分析喹诺酮类药物在妇幼保健医院的临床应用现状,特别是新型的喹诺酮类药物更是具有生物利用度高、t1/2长、血药浓度高、组织分布广等优点,在妇幼保健医院被广泛用于呼吸系统、消化系统感染性疾病的治疗。但是喹诺酮类药物的临床应用增多,其耐药问题也日益突出。如何在妇幼保健医院安全、合理使用喹诺酮类药物是临床医生、药师所面临的重要问题。     

枝原体和尿原体对左氧氟沙星衍生物(YH7)的体外敏感性研究

采用微量稀释法测定了(S)-9氟-2，3-二氢-3-甲基-10-（4-（2-嘧啶）-1-哌嗪基）-7-氧代-7H-吡啶并[1,2,3-de][1,4]苯并恶嗪-6-羧酸（YH7）等氟喹诺酮及大环内酯类、四环素类抗生素对人型支原体（Mh）、口腔枝原体（M.ora）、唾液枝原体（M.sal）、解脲枝原体（Uu）的体外敏感性。结果显示：YH7对Mh、M、ora、M、sal、Uu的最低抑制浓度（MIC）分别为0.5、0.25、0.125、0.125mg/L。它的抑菌活性是氧氟沙星2-16倍，与红霉素、柱晶白霉素相当。Mh、Uu对YH7及交沙霉素不易产生诱导耐药性，而对红霉素和四环素易产生诱导耐药性。而对红霉素升四环素产生耐药的Mh和Uu菌株对红霉素和四环素交叉耐药而对YH7和交沙霉素无交叉耐药。