Graham David Y, Shiotani Akiko
Department of Medicine, Michael E DeBakey Veterans Affairs Medical Center and Baylor College of Medicine, Houston, TX 77030, USA.
Nat Clin Pract Gastroenterol Hepatol. 2008 Jun;5(6):321-31. doi: 10.1038/ncpgasthep1138. Epub 2008 Apr 29.
The prevalence of antimicrobial drug resistance is now so high that all patients infected with Helicobacter pylori should be considered as having resistant infections. Ideally, therapy should be based on pretreatment antibiotic-susceptibility testing but this strategy is not currently practical. At present, clarithromycin-containing triple therapies do not reliably produce a > or =80% cure rate on an intention-to-treat basis and are, therefore, no longer acceptable as empiric therapy. In this Review, we discuss concepts of resistance that have become part of mainstream thinking for other infectious diseases but have not yet become so with regard to H. pylori. We also put data on the pharmacokinetics and pharmacodynamics of the drugs used in H. pylori therapy and the effect of host cytochrome P450 genotypes in context with treatment outcomes. Our primary focus is to address the problem of H. pylori resistance from a novel perspective, which also attempts to anticipate the direction that research will need to take to provide clinicians with reliable approaches to this serious infection. We also discuss current therapies that provide acceptable cure rates when used empirically (i.e. sequential therapy; four-drug, three-antibiotic, non-bismuth-containing 'concomitant' therapy; and bismuth-containing quadruple therapy) and how they might be further improved.
目前，抗菌药物耐药性的流行程度极高，所有感染幽门螺杆菌的患者都应被视为存在耐药感染。理想情况下，治疗应基于治疗前的抗生素敏感性检测，但目前这种策略并不实际可行。目前，含克拉霉素的三联疗法在意向性治疗基础上并不能可靠地产生≥80%的治愈率，因此，不再可接受作为经验性治疗。在本综述中，我们讨论了耐药性的概念，这些概念已成为其他传染病主流思维的一部分，但在幽门螺杆菌方面尚未如此。我们还结合治疗结果阐述了幽门螺杆菌治疗中所用药物的药代动力学和药效学数据以及宿主细胞色素P450基因型的影响。我们的主要重点是从一个新的角度解决幽门螺杆菌耐药性问题，这也试图预测研究需要采取的方向，以便为临床医生提供针对这种严重感染的可靠方法。我们还讨论了经验性使用时能提供可接受治愈率的当前疗法（即序贯疗法；四联、三抗生素、不含铋的“伴随”疗法；以及含铋四联疗法）以及如何进一步改进这些疗法。
