Treatment of active pulmonary tuberculosis in adults: current standards and recent advances. Insights from the Society of Infectious Diseases Pharmacists.
Treatment of active pulmonary tuberculosis in adults: current standards and recent advances. Insights from the Society of Infectious Diseases Pharmacists.
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DOI：
10.1592/phco.29.12.1468
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发表时间：
2009-12
期刊：
影响因子：
4.1
通讯作者：
Gumbo T
中科院分区：
文献类型：
--
作者：
Hall RG;Leff RD;Gumbo T
结核病是一种全球流行病，每年有900万新病例，约200万人死亡。1993年至2007年期间，美国98%以上接受结核病治疗的患者具有药物敏感菌株。药物敏感结核病的标准治疗方案几十年来没有改变，是根据对不同治疗方案的经验观察制定的。直到最近，标准疗法的科学依据的准确性才得到检验。治疗的支柱仍然是异烟肼，利福平和吡嗪酰胺，虽然氟喹诺酮类药物正在研究作为异烟肼的替代品。最近的群体药代动力学研究已经证明了异烟肼、吡嗪酰胺和利福平个体化给药的重要性。异烟肼血清清除率因患者的N-乙酰转移酶2基因 *4（NAT 2 *4）等位基因数量而异。吡嗪酰胺血清清除率已显示随体重增加而增加。利福平的分布容积、清除率和吸收率在患者间和患者内具有广泛的变异性。已经确定了利福平、异烟肼、吡嗪酰胺和氟喹诺酮类药物的微生物药代动力学-药效学（PK-PD）指标和靶点，以优化微生物杀灭并最大限度地降低耐药性。这些PK-PD指数表明，与目前推荐的剂量和给药方案不同的剂量和给药方案可以优化治疗，并可能缩短治疗持续时间。外排泵抑制也正在研究中，以加强一线抗结核药物治疗。合并症如糖尿病和遗传决定的铁超载综合征与患者预后显著恶化相关。对这些和其他患者群体的治疗需要进一步改进。这些患者因素、药代动力学变异性的协变量和PK-PD因素表明，需要对结核病患者进行个体化治疗，以优化结局并缩短治疗持续时间。
Tuberculosis is a global pandemic, with 9 million new cases of the disease and approximately 2 million deaths each year. More than 98% of patients treated for tuberculosis in the United States between 1993 and 2007 had drug-susceptible strains. The standard treatment regimen for drug-susceptible tuberculosis has not changed in decades and was developed on the basis of empiric observations of different treatment regimens. Only recently has the veracity of the scientific basis for standard therapy been examined. The backbone of therapy is still isoniazid, rifampin, and pyrazinamide, although fluoroquinolones are being investigated as a replacement for isoniazid. Recent population pharmacokinetic studies have demonstrated the importance of individualized dosing of isoniazid, pyrazinamide, and rifampin. Isoniazid serum clearance differs depending on the patient’s number of N-acetyltransferase 2 gene *4 (NAT2*4) alleles. Pyrazinamide serum clearance has been shown to increase with increases in body weight. Rifampin’s volume of distribution, clearance, and absorption have wide between-patient and within-patient variability. Microbial pharmacokinetic-pharmacodynamic (PK-PD) indexes and targets to optimize microbial killing and minimize resistance have been identified for rifampin, isoniazid, pyrazinamide, and the fluoroquinolones. These PK-PD indexes suggest that different doses and dosing schedules than those currently recommended could optimize therapy and perhaps shorten duration of therapy. Efflux pump inhibition is also being investigated to enhance first-line antituberculosis drug therapy. Comorbid conditions such as diabetes mellitus and genetically determined iron overload syndromes have been associated with significantly worse patient outcomes. Therapy for these and other patient groups needs further improvement. These patient factors, the covariates for pharmacokinetic variability, and PK-PD factors suggest the need to individualize therapy for patients with tuberculosis in order to optimize outcomes and reduce the duration of therapy.
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影响因子：
4.9
作者：
Almeida, Deepak;Nuermberger, Eric;Grosset, Jacques
通讯作者：
Grosset, Jacques
DOI：
10.1164/rccm.200605-637oc
发表时间：
2006-11-15
影响因子：
24.7
作者：
Chang, Kwok C.;Leung, Chi C.;Tam, Cheuk M.
通讯作者：
Tam, Cheuk M.
DOI：
10.1016/0041-3879(83)90035-1
发表时间：
1983-01-01
期刊：
TUBERCLE
影响因子：
--
作者：
ALLEN, BW;MITCHISON, DA;GIRLING, DJ
通讯作者：
GIRLING, DJ
DOI：
10.1016/0041-3879(74)90003-8
发表时间：
1974-01-01
期刊：
TUBERCLE
影响因子：
--
作者：
ANDREWS, RH;JENKINS, PA;SOMNER, AR
通讯作者：
SOMNER, AR
影响因子：
--
作者：
FINEGOLD, SM
通讯作者：
FINEGOLD, SM