Therapy for Helicobacter pylori infection can be improved -: Sequential therapy and beyond
Therapy for Helicobacter pylori infection can be improved -: Sequential therapy and beyond
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DOI：
10.2165/00003495-200868060-00001
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发表时间：
2008-01-01
期刊：
影响因子：
11.5
通讯作者：
Yamaoka, Yoshio
中科院分区：
文献类型：
--
作者：
Graham, David Y.;Lu, Hong;Yamaoka, Yoshio
与其他细菌感染一样，幽门螺杆菌感染的成功治疗取决于使用细菌敏感的抗菌剂。在本文中，我们对临床试验的结果使用了建议的报告卡分级方案（即A、B、C、D、F级），其中意向治疗治愈率为>95% = A, 90-95% = B, 85-89% = C, 81-84% = D和< 81% = F。治疗的目标是持续治愈>95%的患者（例如提供A级结果）。像结核病一样，幽门螺旋杆菌感染很难治愈，成功的治疗通常需要同时使用几种抗菌药物。治疗的持续时间也很重要，取决于是否存在耐药性；14天通常是最好的。除少数例外情况外，世界范围内不断增加的大环内酯类药物耐药性现在破坏了传统三联疗法（例如质子泵抑制剂[PPI]、克拉霉素和阿莫西林）的有效性，并且在大多数地区，治愈率已下降到不可接受的水平（例如F级）。序贯疗法的发展是对这个问题的一种回应。序贯疗法在头对头的研究中反复显示优于传统的三联疗法。序贯治疗，如最初所述，是双疗法（PPI加阿莫西林）的序贯给药，然后是巴佐利型三联疗法（PPI加克拉霉素和替硝唑），已被证明在克拉霉素耐药的地方特别有用。然而，最初序贯治疗的治愈率为B级，并可能通过改变剂量、持续时间或给药进一步提高治愈率，例如在三联治疗组中继续使用阿莫西林。顺序方法也可能比必要的更复杂，基于这样一个事实，即同样的四种药物也被同时使用（至少有9篇出版物，有700名患者）作为四联疗法取得了巨大的成功。本文讨论了治疗方法在现代的抗菌素耐药性是一个日益严重的问题，传统的三联疗法不再是一个可接受的初始选择。讨论了实现可接受的根除率（例如A级或B级结果）的方法，具体地说，顺序治疗在概念上和实践上都被考虑。就序贯治疗如何改进成为a级治疗以及如何识别可能产生不可接受结果的情况提出了建议。讨论了现有药物的新用途，并提出了后续随机比较以克服表型和基因型耐药的建议。我们建议将重点从比较研究（旨在证明新疗法优于已知的劣疗法）转变为要求有效疗法达到或超过预先规定的成功水平（即a级或B级结果）。这样做，再加上减少对建议对制药业的影响的关注，应该为临床医生提供更高质量的信息，并提高医疗保健和治疗建议的质量。最终，很少或根本没有理由进行包括已知结果低得不可接受的手臂的比较测试。幽门螺杆菌胃炎是一种感染性疾病，应作为感染性疾病来对待和治疗。
As with other bacterial infections, successful treatment of Helicobacter pylori infections depends on the use of antibacterial agents to which the organism is susceptible. In this article, we use the proposed report card grading scheme (i.e. grade A, B, C, D, F) for the outcome of clinical trials, where intention-to-treat cure rates > 95% = A, 90-95% = B, 85-89% = C, 81-84% = D and < 81% = F. The goal of therapy is to consistently cure >95% of patients (e.g. provide grade A results). Like tuberculosis, H. pylori infections are difficult to cure and successful treatment generally requires the administration of several antibacterial agents simultaneously. Duration of therapy is also important and depends upon whether resistance is present; 14 days is often best. With few exceptions, worldwide increasing macrolide resistance now undermines the effectiveness of the legacy triple therapy (e.g. a proton pump inhibitor [PPI], clarithromycin and amoxicillin) and, in most areas, cure rates have declined to unacceptable levels (e.g. grade F).The development of sequential therapy was one response to this problem. Sequential therapy has repeatedly been shown in head-to-head studies to be superior to legacy triple therapy. Sequential therapy, as originally described, is the sequential administration of a dual therapy (a PPI plus amoxicillin) followed by a Bazzoli-type triple therapy (a PPI plus clarithromycin and tinidazole) and has been shown to be especially useful where there is clarithromycin resistance. However, the cure rates of the original sequential treatment are grade B and can probably be further improved by changes in dose, duration or administration, such as by continuing the amoxicillin into the triple therapy arm. The sequential approach may also be more complicated than necessary, based on the fact that the same four drugs have also been given concomitantly (at least nine publications with > 700 patients) as a quadruple therapy with excellent success.This article discusses the approach to therapy in the modem era where antimicrobial resistance is an increasing problem and legacy triple therapy is no longer an acceptable initial choice. Methods to achieve acceptable eradication rates (e.g. grade A or B results) are discussed and, specifically, sequential therapy is considered both conceptually and practically. Suggestions are provided regarding how sequential therapy might be improved to become a grade A therapy as well as how to identify situations where it can be expected to yield unacceptable results. New uses for current drugs are discussed and suggestions for subsequent randomized comparisons to overcome phenotypic and genotypic resistance are given. We propose a change in focus from comparative studies (designed to prove that a new therapy is superior to a known inferior therapy) to demanding that efficacious therapies meet or exceed a pre-specified level of success (i.e. grade A or B result). To do so, coupled with less concern about the effect of recommendations on the pharmaceutical industry, should provide clinicians with much higher quality information, and improve the quality of medical care and recommendations regarding treatment. Ultimately, there is little or no justification for comparative testing that includes an arm with known unacceptably low results. H. pylori gastritis is an infectious disease and should be approached and treated as such.