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Correlation between rpoB gene mutation in Mycobacterium avium subspecies paratuberculosis and clinical rifabutin and rifampicin resistance for treatment of Crohn’s disease

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World Journal of Gastroenterology 2008年第17期14卷 2723-2730页

作者： Daniel R Beckler Sammer Elwasila George Ghobrial John F Valentine Saleh A Naser Department of Molecular Biology and Microbiology Burnett School of Biomedical Sciences Center for Biomolecular Sciences College of Medicine University of Central Florida Department of Medicine University of Florida Gainesville

AIM： To investigate overlapping regions of the rpoB gene previously involved with rifamycin resistance in M. tuberculosis and seek correlation between rpoB mutations in dinical MAP strains with susceptibility to RIF and RFB. METHODS： We designed a molecular-based PCR method for the evaluation of rifabutin （RFB） and rifampicin （RIF） resistance based on probable determinant regions within the rpoB gene of MAP, including the 81 bp variable site located between nucleotides 1363 and 1443. The minimum inhibitory concentration （MIC） for RIF was also determined against 11 MAP isolates in attempt to seek correlation with rpoB sequences. RESULTS： We determined that MAP strain 18 had an MIC of 〉 30 mg/L and ≤ 5 mg/L for RIF and RFB respectively, and a significant and novel rpoB mutation C1367T, compared to an MIC of ≤ 1.0 mg/L for both drugs in the wild type MAP. The 30-fold increase in the MIC was a direct result of the rpoB mutation C1367T, which caused an amino acid change Thr456 to Ile456 in the drug＇s binding site. In addition, MAP strain 185 contained five silent rpoB mutations and exhibited an MIC comparable to the wild-type. Moreover, our in vitro selected mutation in MAP strain UCF5 resulted in the generation of a new resistant strain （UCF5-RIF16r） that possessed T1442C rpoB mutation and an MIC 〉 30 mg/L and 〉 10 mg/L for RIF and RFB respectively. Sequencing of the entire rpoB gene in MAP strains UCF4, 18, and UCF5-RIF16r revealed an rpoB mutation A2284C further downstream of the 81 bp variable region in UCF4, accounting for observed slight increase in MIC. In addition, no other significant mutations were found in strains 18 and UCF-RIF16r. CONCLUSION： The data clearly illustrates that clinical and in vitro-selected MAP mutants with rpoB mutations result in resistance to RIF and RFB, and that a single amino acid change in the beta subunit may have a significant impact on RIF resistance. Unconventional drug susceptibility testing such as our molecular approach wi

关键词： Mycobacterium paratuberculosis Crohn's disease rifabutin Rifampicin rpoB Minimum inhibitoryconcentration

利福霉素衍生物rifabutin的临床药理研究进展

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中国临床药理学与治疗学 2006年第1期11卷 1-9页

作者：李朝旭张锦楠任爽高承英孙怡王雪首都医科大学化学生物学与药学院化学生物学系北京100069

rifabutin(RBT)是一种类似于利福平(RIF)的利福霉素衍生物。1992年被美国FDA批准用于治疗和预防发生在AIDS患者上的鸟分枝杆菌(MAC)感染,随后许多国家相继批准使用该药。但是后来RBT已不仅被用于预防治疗MAC,还用于治疗肺结核以及幽门... 详细信息

rifabutin(RBT)是一种类似于利福平(RIF)的利福霉素衍生物。1992年被美国FDA批准用于治疗和预防发生在AIDS患者上的鸟分枝杆菌(MAC)感染,随后许多国家相继批准使用该药。但是后来RBT已不仅被用于预防治疗MAC,还用于治疗肺结核以及幽门螺杆菌(HP)感染。正是由于该药相对于其他利福霉素类药物的高度亲脂性和较弱的CYP450诱导作用使得它成功应用于临床多种疾病的治疗,尤其是和多种抗生素联合用药时,不仅部分解决了传统抗生素的细菌耐受性问题而且增加了临床联合用药的安全性。本文旨在阐述有关的Ri-fabutin的临床药理以及相关方面的研究进展,以便指导今后临床用药。

关键词： rifabutin CYP450 药物相互作用 MAC 肺结核 Helicobacter pylori

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抗菌剂rifabutin

国外新药介绍 1994年第2期 17-18页

应用rifabutin和链霉素治疗Crohn氏病

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国外医药(抗生素分册) 1989年第1期 70-70页

作者：徐积恩

作者曾连续报道从Crohn氏病的组织中分离到分枝杆菌,并从慢性消耗性腹泻的猴中分离到类似微生物,该分枝杆菌在肉汤中对链霉素、万古霉素、利福平、氯氟齐明、头孢唑啉、丁胺卡那霉素,rifabutin和卡那霉素敏感。用丁胺卡那霉素治疗90天,... 详细信息

作者曾连续报道从Crohn氏病的组织中分离到分枝杆菌,并从慢性消耗性腹泻的猴中分离到类似微生物,该分枝杆菌在肉汤中对链霉素、万古霉素、利福平、氯氟齐明、头孢唑啉、丁胺卡那霉素,rifabutin和卡那霉素敏感。用丁胺卡那霉素治疗90天,用rifabutin治疗12～22个月不等,使组织学和细菌学指标转为正常。作者进一步选用链霉素(肌注,每周5日,每日1克,治疗2～4月),同时每日给300mgrifabutin,对难治性

关键词：链霉素抗结核抗菌素 rifabutin Crohn

rifabutin治疗回肠切除后复发性Crohn氏病

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国外医药(抗生素分册) 1989年第1期 70-70页

作者：徐积恩

最近的研究表明Crohn氏病与非典型性分枝杆菌有关,一种利福平的新衍生物rifabutin对这些微生物有高度活性。作者还证明手术后新形成终端回肠的Crohn氏病复发可作为研究对Crohn氏病药物的模型。作者报道16名患者(8男8女,平均年龄32岁),... 详细信息

最近的研究表明Crohn氏病与非典型性分枝杆菌有关,一种利福平的新衍生物rifabutin对这些微生物有高度活性。作者还证明手术后新形成终端回肠的Crohn氏病复发可作为研究对Crohn氏病药物的模型。作者报道16名患者(8男8女,平均年龄32岁),一年前都经过手术,治疗前均经内窥镜检查示有严重的新终端回肠损害。经rifabutin(5mg/kg)和乙胺丁醇(15mg/kg)给药6个月。有6例因副作用撤出研究(副作用包括白血球减少、流感样症状)。剩下10例中7例完成治疗,但本研究证明,6个月的rifabutin和乙胺丁醇联合治疗对复发性

关键词：复发性乙胺丁醇乙二胺 Crohn rifabutin

“Rescue” regimens after Helicobacter pylori treatment failure

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World Journal of Gastroenterology 2008年第35期14卷 5385-5402页

作者： Javier P Gisbert Gastroenterology Unit Hospital Universitario de la Princesa and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y DigestivasMadridSpain

Helicobacter pylori (H pylori) infection is the main cause of gastritis, gastroduodenal ulcer disease, and gastric cancer. After more than 20 years of experience in H pylori treatment, in my opinion, the ideal regimen to treat this infection is still to be found. Currently, apart from having to know first-line eradication regimens well, we must also be prepared to face treatment failures. Therefore, in designing a treatment strategy we should not focus on the results of primary therapy alone, but also on the final (overall) eradication rate. The choice of a "rescue" treatment depends on which treatment is used initially. If a clarithromycin- based regimen was used initially, a subsequent metronidazole-based treatment (quadruple therapy) may be used afterwards, and then a levofloxacin- based combination would be a third "rescue" option. Alternatively, it has recently been suggested that levofloxacin-based rescue therapy constitutes an encouraging second-line strategy, representing an alternative to quadruple therapy in patients with previous PPI-clarithromycin-amoxicillin failure, with the advantage of efficacy, simplicity and safety. In this case, a quadruple regimen may be reserved as a third-line rescue option. Finally, rifabutin-based rescue therapy constitutes an encouraging empirical fourth- line strategy after multiple previous eradication failures with key antibiotics such as amoxicillin, clarithromycin, metronidazole, tetracycline, and levofloxacin. Even after two consecutive failures, several studies have demonstrated that H pylori eradication can finally be achieved in almost all patients if several rescue therapies are consecutively given. Therefore, the attitude in H pylori eradication therapy failure, evenafter two or more unsuccessful attempts, should be to fight and not to surrender.

关键词： Helicobacter pylori Rescue Salvage rifabutin Levofloxacin

Second and third line treatment options for Helicobacter pylori eradication

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World Journal of Gastroenterology 2014年第6期20卷 1517-1528页

作者： Mingjun Song Tiing Leong Ang Department of Gastroenterology Changi General Hospital

Helicobacter pylori is a highly successful bacterium with a high global prevalence and the infection carries significant disease burden. It is also becoming increasingly difficult to eradicate and the main reason for this is growing primary antibiotic resistance rates in a world where antibiotics are frequently prescribed and readily available. Despite knowing much more about the bacterium since its discovery, such as its genomic makeup and pathogenesis, we have seen declining treatment success. Therefore, clinicians today must be prepared to face one, two or even multiple treatment failures, and should be equipped with sufficient knowledge to decide on the appropriate salvage therapy when this happens. This article discusses the factors contributing to treatment failure and reviews the second and thirdline treatment strategies that have been investigated. Established empiric second line treatment options include both bismuth based quadruple therapy and levofloxacin based triple therapy. Antibiotic testing is recommended prior to initiating third line treatment. In the event that antibiotic susceptibility testing is unavailable, third line treatment options include rifabutin, rifaximin and sitafloxacin based therapies.

关键词： Helicobacter pylori Treatment failure Salvage therapy Drug resistance Microbial Bismuth Ofloxacin Moxifloxacin Metronidazole rifabutin Rifaximin Sitafloxacin

Third-line rescue therapy for Helicobacter pylori infection

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World Journal of Gastroenterology 2006年第15期12卷 2313-2319页

作者： Rossella Cianci Massimo Montalto Franco Pandolfi Giovan Battista Gasbarrini Giovanni Cammarota Department of Internal Medicine Endoscopy Unit Catholic University of Sacred HeartRomeItaly

H pylori gastric infection is one of the most prevalent infectious diseases worldwide. The discovery that most upper gastrointestinal diseases are related to Hpylori infection and therefore can be treated with antibiotics is an important medical advance. Currently, a first-line triple therapy based on proton pump inhibitor （PPI） or ranitidine bismuth citrate （RBC） plus two antibiotics （darithromycin and amoxicillin or nitroimidazole） is recommended by all consensus conferences and guidelines. Even with the correct use of this drug combination, infection can not be eradicated in up to 23% of patients. Therefore, several second line therapies have been recommended. A 7 d quadruple therapy based on PPI, bismuth, tetracycline and metronidazole is the more frequently accepted. However, with second-line therapy, bacterial eradication may fail in up to 40% of cases. When Hpylori eradication is striclly indicated the choice of further treatment is controversial. Currently, a standard third-line therapy is lacking and various protocols have been proposed. Even after two consecutive failures, the most recent literature data have demonsbated that Hpylori eradication can be achieved in almost all patients, even when antibiotic susceptibility is not tested. Different possibilities of empirical treatment exist and the available third-line strategies are herein reviewed.

关键词： Helicobacter pylori Third-line rescue therapy Antimicrobial resistance Levofloxacin rifabutin Furazolidone Doxycycline