Tuberculosis pharmacotherapy: strategies to optimize patient care.
Tuberculosis pharmacotherapy: strategies to optimize patient care.
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结核病药物治疗：优化患者护理的策略。
DOI：
10.1517/14656560802694564
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发表时间：
2009-02
影响因子：
3.2
通讯作者：
中科院分区：
文献类型：
--
作者：
结核病的治疗是一门成熟的学科，在全球积累了60多年的临床经验。然而，对药物敏感的结核病进行必要的多药治疗持续6个月，而且从未根据现行标准进行优化。耐多药结核病和合并感染艾滋病毒的人的结核病带来了额外的治疗挑战。本文综述了现有药物和新化合物在缩短或改善结核病治疗方面可能发挥的作用。缩短治疗时间的关键似乎是杀菌活性，即药物杀死分枝杆菌的能力，这种能力在多药治疗的最初几天持续存在。在现有的抗结核病药物中，利福霉素在艾滋病毒感染和未感染艾滋病毒的人群中都具有最大的缩短治疗和改善结果的潜力，而不会大幅增加毒性。正在进行或计划中的临床研究得到了体外、动物和人类证据的支持，这些证据表明，在每日剂量增加的情况下，灭菌活性增加，而毒性没有显著增加。氟喹诺酮类药物似乎也具有显著的杀菌活性。目前至少有两类成员正在接受评估，以缩短使用不同一线药物组合的治疗时间。然而，鉴于对氟喹诺酮耐药突变株的明显快速选择，严重不良事件的相对频率，以及人们认为有必要将氟喹诺酮类药物‘保留’用于治疗耐药结核病，它们在结核病治疗中的确切作用仍有待确定。其他可能的改善可能来自吸入给药或分次给药(利奈唑胺)，这些药物的毒性(乙硫酰胺)或缺乏吸收(氨基糖苷类和多肽)阻碍了最有效的口服剂量，每天一次。具有新作用机制的新型药物，如硝基咪唑并吡喃和二芳基喹啉等，可能很快就会为改善耐药结核病的治疗和/或缩短对药物敏感的结核病的治疗提供机会。与过去30年中的任何时候相比，目前存在着更多改善结核病治疗的潜在选择。结核病药物治疗的挑战是设计耐受性好、有效、疗程短的方案，这些方案可以在不同的患者群体中成功地用于治疗耐药和耐药结核病。
The treatment of tuberculosis (TB) is a mature discipline, with over 60 years of clinical experience accrued across the globe. The requisite multidrug treatment of drug-susceptible TB, however, lasts six months and has never been optimized according to current standards. Multi-drug resistant tuberculosis and tuberculosis in individuals coinfected with HIV present additional treatment challenges. This article reviews the role that existing drugs and new compounds could have in shortening or improving treatment for tuberculosis. The key to treatment shortening appears to be sterilizing activity, or the ability of drugs to kill mycobacteria that persist after the initial days of multidrug treatment. Among existing anti-TB drugs, the rifamycins hold the greatest potential for shortening treatment and improving outcomes, in both HIV-infected and HIV-uninfected populations, without dramatic increases in toxicity. Clinical studies underway or being planned, are supported by in vitro, animal, and human evidence of increased sterilizing activity–without significant increases in toxicity–at elevated daily doses. Fluoroquinolones also appear to have significant sterilizing activity. At least two class members are currently under evaluation for treatment shortening with different combinations of first-line drugs. However, in light of apparent rapid selection for fluoroquinolone-resistant mutants, relative frequency of serious adverse events, and a perceived need to ‘reserve’ fluoroquinolones for the treatment of drug-resistant TB, their exact role in TB treatment remains to be determined. Other possible improvements may come from inhaled delivery or split dosing (linezolid) of anti-TB drugs for which toxicity (ethionamide) or lack of absorption (aminoglycosides and polypeptides) precludes delivery of maximally effective, oral doses, once daily. New classes of drugs with novel mechanisms of action, nitroimidazopyrans and a diarylquinoline, among others, may soon provide opportunities for improving treatment of drug-resistant TB and/or shortening treatment of drug-susceptible TB. More potential options for improved TB treatment currently exist than at any other time in the last 30 years. The challenge in TB pharmacotherapy is to devise well-tolerated, efficacious, short-duration regimens that can be used successfully against drug-resistant and drug-resistant TB in a heterogeneous population of patients.
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影响因子：
11.5
作者：
Berning, SE
通讯作者：
Berning, SE
影响因子：
7.3
作者：
Biava, Mariangela;Cesare Porretta, Giulio;Botta, Maurizio
通讯作者：
Botta, Maurizio
影响因子：
56.9
作者：
Andries, K;Verhasselt, P;Jarlier, V
通讯作者：
Jarlier, V
DOI：
10.1016/s1472-9792(08)70018-0
发表时间：
2008-03-01
期刊：
Tuberculosis (Edinburgh, Scotland)
影响因子：
--
作者：
通讯作者：
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影响因子：
2.9
作者：
Antal, EJ;Hendershot, PE;Donaldson, KM
通讯作者：
Donaldson, KM