Coll Pere
Servei de Microbiologia, Hospital de la Santa Creu i Sant Pau, Barcelona, España.
Enferm Infecc Microbiol Clin. 2009 Oct;27(8):474-80. doi: 10.1016/j.eimc.2009.06.010. Epub 2009 Sep 18.
Treatment for Mycobacterium tuberculosis must be lengthy because populations of this bacillus differ in metabolic activity, and it must include various associated drugs, since spontaneous chromosome mutations can give rise to drug resistance. The multiresistant phenotype emerges with sequential acquisition of mutations in several independent loci. Thus, the main challenges in tuberculosis treatment are resistant strains and reductions in treatment duration and dose to facilitate adherence on the part of the patient. The drugs should be fast acting, active against resistant strains, and able to eradicate slowly metabolizing populations. Progress in recent years has led to the development of analogs of first-line antituberculosis drugs with longer dosing intervals (rifamycin derivatives) or shorter treatment courses (moxifloxacin, gatifloxacin). Nonetheless, new drugs that additionally have novel mechanisms of action and no cross-resistance to current first-line drugs are needed. This review describes the characteristics, activity, resistance mechanisms, and side effects associated with antituberculosis drugs.
治疗结核分枝杆菌必须采用长疗程,因为这种杆菌群体的代谢活性存在差异,而且必须使用多种联合药物,因为自发的染色体突变会导致耐药性。多重耐药表型是通过在几个独立位点上依次获得突变而出现的。因此,结核病治疗的主要挑战是耐药菌株以及缩短治疗疗程和剂量以促进患者的依从性。这些药物应起效迅速,对耐药菌株有效,并能够根除代谢缓慢的菌群体。近年来的进展已促使开发出给药间隔更长的一线抗结核药物类似物(利福霉素衍生物)或疗程更短的药物(莫西沙星、加替沙星)。尽管如此,仍需要具有新作用机制且与当前一线药物无交叉耐药性的新药。本综述描述了与抗结核药物相关的特性、活性、耐药机制和副作用。