Penetration of fusidic acid and rifampicin into cerebrospinal fluid in low-grade inflammatory meningitis caused by Staphylococcus epidermidis

Cerebrospinal fluid (CSF) concentration-time curves of rifampicin and fusidic acid were studied in a patient with post-operative meningitis caused by Staphylococcus epidermidis. The patient was treated with this combination of antimicrobial agents because of a severe hypersensitivity reaction to vancomycin. Peak CSF concentrations of rifampicin exceeded the MIC by > 60-fold, while those of fusidic acid just reached the MIC. CSF concentrations of fusidic acid were relatively stable within the range reported for patients with uninflamed meninges, but serum levels were surprisingly low. An increase in the metabolism of fusidic acid induced by rifampicin cannot be excluded.     

利福平引起的急性肾功能衰竭及其机制研究(3例报告及文献复习)

目的：探讨利福平致急性肾功能衰竭的临床病理特点及其发病机制。方法：对3例因利福平所致的急性肾衰竭患者的临床、肾脏病理进行分析，并采用抗人球蛋白试验方法检测患者的抗利福平抗体。结果：3例患者均有前驱感染史，临床主要表现为发热、胃肠道症状，随即出现无尿，伴随肾功能损害、血小板减低及溶血性贫血，部分伴有肝功能损害。肾活检3例均为急性肾小管坏死。3例的血清抗利福平抗体检测均为阳性。结论：利福平可引起急性肾衰竭，对应用利福平的患者应加强对肾功能的监测，肾脏病理及血清抗利福平抗体的检测有助于确诊。     

In-vitro activity of rifabutin against rifampicin-resistant Mycobacterium tuberculosis isolates with known rpoB mutations

The relationship between resistance to rifampicin and rifabutin and genetic alterations in the rpoB gene of 41 rifampicin-resistant isolates of Mycobacterium tuberculosis was evaluated. Although 35 isolates with rifampicin MICs > or = 32 mg/L were also rifabutin-resistant, six isolates with rifampicin MICs of 2-16 mg/L were susceptible to rifabutin (MIC < or = 0.5 mg/L). Mutations Asp516Val, Asp516Tyr, Leu533Pro and the double mutation Met515Ile and Leu533Pro influenced susceptibility to rifampicin, but not to rifabutin. All mutations at codons 531 and 526, except one isolate with a His526Cys mutation, correlated with resistance to both compounds.     

Treatment of acute post-surgical infection of joint arthroplasty

The best antibiotic regimen for acute prosthetic joint infection, treated without removal of the implant, has not been well-defined. This study describes the use of a protocol based on oral rifampicin combinations to treat 47 cases that were followed prospectively for a 2-year period. The regimen used most commonly was levofloxacin 500 mg/24 h plus rifampicin 600 mg/24 h for a mean duration of 2.7 ± 1 months. The cure rate was 76.9%, and the only independent risk-factor associated with treatment failure was infection caused by methicillin-resistant Staphylococcus aureus or Enterococcus spp. (OR 17.6, p 0.003). Overall, the results suggested that use of oral antibiotics, including rifampicin, for 2–3 months was a good treatment option.     

中药抗药源性肝损伤评价模型及作用机制研究进展

肝脏是药物在机体内代谢的主要场所。药源性肝损伤（drug-induced liver injury,DILI）是药物过量或不当使用导致的机体不良反应之一。非甾体类抗炎药、抗菌药等均可能引起DILI。DILI发生机制主要与细胞色素P450酶、线粒体功能障碍、药物代谢反应、氧化应激、炎症反应等密切相关。中药可通过抑制氧化应激、炎症反应、减少细胞凋亡与影响细胞色素P450酶系统等发挥治疗肝损伤作用。通过对DILI发生机制、动物模型建立方法及中药干预机制等方面进行总结归纳,为DILI动物模型的合理选择及中药防治机制研究提供参考。     

利福霉素类抗生素的晶型与血（尿）药浓度

目的：探讨利福霉素类抗生素的衍生物（利福平,利福定,利福喷丁）的晶型与血（尿）药浓度的关系。方法：通过正常人空腹口服各不同型晶粉,定时收集血、尿标本,用杯碟法测定血、尿药含量。结果：同一药物的不同晶型粉,显示出各自不同的结构图形、溶解度及生物有效度的特性。结论：凡是稳定的晶型均具恒定的结构及生物有效度,利福霉素类药物的含水量,对其晶型的稳定性至关重要,干燥失重,不是越低越好。     

复方利福平片溶出度测定方法的研究

目的 建立复方利福平片的溶出度测定方法。方法 采用溶出度测定法第二法，以水为溶剂，转速为50r／min，经45min取样，紫外分光光度法在474nm处测定利福平的溶出量，溶出限度为标示量的75％。结果利福平在10．3—36．1μg／ml范围内线性关系良好(r＝1．0000)，平均回收率99．8％。结论 本方法准确、快速、简便。通过测定复方利福平片的溶出度可有效检测其制剂工艺水平。     

Simultaneous quantification of isoniazid,rifampicin, ethambutol and pyrazinamide by liquid chromatography/tandem mass spectrometry

A remediable cause of poor treatment response in drug‐susceptible tuberculosis (TB) patients may be low plasma levels of one or more of the first‐line anti‐TB drugs. The aim of this work was to develop an accurate and precise LC‐MS/MS method for simultaneous quantification of all four first‐line anti‐TB drugs in plasma suitable for therapeutic drug monitoring (TDM). To adjust for degradation and losses during sample preparation, isotopically labeled compounds were used as internal standards. Plasma samples spiked with internal standards were extracted using protein precipitation with methanol and acetonitrile. Simultaneous separation of all four drugs was accomplished with a Chromolith Reversed‐Phase column and mobile phases consisting of water, methanol, ammonium acetate and formic acid with subsequent mass spectrometric quantification. The linear range of the calibration curve for isoniazid was 0.5–10 mg/L, for rifampicin 0.75–30 mg/L, for ethambutol 0.25–10 mg/L and for pyrazinamide 4–80 mg/L. The lower limit of quantification was 0.5 mg/L, 0.75 mg/L, 0.25 mg/L and 4.0 mg/L, respectively. Precision estimated by the coefficient of variation was <15% for all four drugs. The LC‐MS/MS method can readily be used for simultaneous quantification of first‐line anti‐TB drugs in plasma and is well suited for TDM.     

Rifampicin reverses nicardipine effect inducing uncontrolled essential hypertension

Dihydropyridine calcium‐channel blockers are a known substrate for the cytochrome P450 isoform 3A4. Rifampicin, an antitubercular agent, is one of the most potent inducers of hepatic and intestinal CYP3A4 thus increasing dihydropyridine metabolism. We report a case of a 67‐year‐old hypertensive female treated with a four‐drug antihypertensive regimen including a dihydropyridine (nicardipine 50 mg bid), who was admitted for septic arthritis of the knee requiring antibiotic treatment with teicoplanin 400 mg od and rifampicin 600 mg bid. Six days after rifampicin initiation, she presented with Posterior Reversible Encephalopathy Syndrome due to uncontrolled hypertension. We hypothesized that disequilibrium of previously controlled hypertension was partially due to nicardipine ineffectiveness. Plasma nicardipine concentration was assessed through high‐performance liquid chromatography 5 hours after coadministration of the two drugs and proved undetectable.