Graham D Y, de Boer W A, Tytgat G N
Department of Medicine, Veterans Affairs Medical Center, Houston, Texas 77030, USA.
Am J Gastroenterol. 1996 Jun;91(6):1072-6.
The development of effective therapies for the treatment of Helicobacter pylori infection has been a long and arduous process. There is considerable confusion about which is the best.
We review approaches to understanding the results of trials evaluating potentially new therapies and those comparing two or more potentially good regimens with particular emphasis on the role of antimicrobial resistance on the outcome of therapy.
Antimicrobial resistance in vitro does not always correlate with poor results with multi-drug treatment regimes. Although it is not known if clinical resistance defined as failure of a therapy might be a better predictive of subsequent failure, overall effectiveness is influenced most strongly by the drug with the poorest cure rates in the presence of resistant microorganisms. Development of resistance is reduced in multiple drug therapies. Bismuth may be an especially useful antimicrobial in this regard because it is an effective topical therapy that markedly reduces the bacterial load. Resistance to antimicrobials can be thought of as a statistical event estimated as a proportion of the H.pylori population in the stomach (e.g., 1 in 10(8) bacteria). Elimination of most organisms with the first dose of bismuth might decrease likelihood of survival of resistant strains that were already present.
Results of large clinical trials are needed to provide accurate estimation concerning the effectiveness of the different treatment regimes using different dosages, dosing intervals, and duration of therapy. For interpretation and comparison, clinical trials must report the overall effectiveness as well as effectiveness of the regimen separately for those with resistant and sensitive H.pylori.
开发有效的幽门螺杆菌感染治疗方法是一个漫长而艰巨的过程。对于哪种方法最佳存在相当大的困惑。
我们回顾了理解评估潜在新疗法的试验结果以及比较两种或更多潜在有效治疗方案的方法,特别强调了抗菌药物耐药性对治疗结果的作用。
体外抗菌药物耐药性并不总是与多药治疗方案的不良结果相关。虽然尚不清楚定义为治疗失败的临床耐药性是否可能是后续失败的更好预测指标,但在存在耐药微生物的情况下,总体有效性受治愈率最差的药物影响最大。多药疗法可降低耐药性的产生。在这方面,铋可能是一种特别有用的抗菌药物,因为它是一种有效的局部治疗方法,可显著降低细菌载量。对抗菌药物的耐药性可被视为一种统计事件,以胃中幽门螺杆菌群体的比例来估计(例如,每10⁸个细菌中有1个)。首剂铋消除大多数生物体可能会降低已存在的耐药菌株存活的可能性。
需要大型临床试验的结果来准确估计使用不同剂量、给药间隔和治疗持续时间的不同治疗方案的有效性。为了进行解释和比较,临床试验必须分别报告对耐药和敏感幽门螺杆菌患者的总体有效性以及治疗方案的有效性。