Ierardi Enzo, Giorgio Floriana, Iannone Andrea, Losurdo Giuseppe, Principi Mariabeatrice, Barone Michele, Pisani Antonio, Di Leo Alfredo
Enzo Ierardi, Floriana Giorgio, Andrea Iannone, Giuseppe Losurdo, Mariabeatrice Principi, Michele Barone, Antonio Pisani, Alfredo Di Leo, Gastroenterology Section, Department of Emergency and Organ Transplantation, University of Bari, 70124 Bari, Italy.
World J Gastroenterol. 2017 Apr 14;23(14):2453-2458. doi: 10.3748/wjg.v23.i14.2453.
The main problem of () infection management is linked to antibiotic resistances. This phenomenon has grown in the last decade, inducing a dramatic decline in conventional regimen effectiveness. The causes of resistance are point mutations in bacterial DNA, which interfere with antibiotic mechanism of action, especially clarithromycin and levofloxacin. Therefore, international guidelines have recently discouraged their use in areas with a relevant resistance percentage, suggesting first-line schedules with expected high eradication rates, ., bismuth containing or non-bismuth quadruple therapies. These regimens require the daily assumption of a large number of tablets. Consequently, a complete adherence is expected only in subjects who may be motivated by the presence of major disorders. However, an incomplete adherence to antibiotic therapies may lead to resistance onset, since sub-inhibitory concentrations could stimulate the selection of resistant mutants. Of note, a recent meta-analysis suggests that susceptibility tests may be more useful for the choice of first than second-line or rescue treatment. Additionally, susceptibility guided therapy has been demonstrated to be highly effective and superior to empiric treatments by both meta-analyses and recent clinical studies. Conventional susceptibility test is represented by culture and antibiogram. However, the method is not available everywhere mainly for methodology-related factors and fails to detect hetero-resistances. Polymerase chain reaction (PCR)-based, culture-free techniques on gastric biopsy samples are accurate in finding even minimal traces of genotypic resistant strains and hetero-resistant status by the identification of specific point mutations. The need for an invasive endoscopic procedure has been the most important limit to their spread. A further step has, moreover, been the detection of point mutations in bacterial DNA fecal samples. Few studies on clarithromycin susceptibility have shown an overall high sensitivity and specificity when compared with culture or PCR on gastric biopsies. On these bases, two commercial tests are now available although they have shown some controversial findings. A novel PCR method showed a full concordance between tissue and stool results in a preliminary experience. In conclusion, despite poor validation, there is increasing evidence of a potential availability of noninvasive investigations able to detect resistances to antibiotics. These kinds of analysis are currently at a very early phase of development and caution should be paid about their clinical application. Only further studies aimed to evaluate their sensitivity and specificity will afford novel data for solid considerations. Nevertheless, noninvasive molecular tests may improve patient compliance, time/cost of infection management and therapeutic outcome. Moreover, the potential risk of a future increase of resistance to quadruple regimens as a consequence of their use on large scale and incomplete patient adherence could be avoided.
（）感染管理的主要问题与抗生素耐药性相关。这一现象在过去十年中不断加剧，导致传统治疗方案的有效性急剧下降。耐药性的原因是细菌DNA中的点突变，这会干扰抗生素的作用机制，尤其是克拉霉素和左氧氟沙星。因此，国际指南最近不鼓励在耐药率较高的地区使用它们，建议采用预期根除率较高的一线治疗方案，即含铋或不含铋的四联疗法。这些方案需要每天服用大量药片。因此，只有那些因患有严重疾病而有动力的患者才有望完全依从。然而，抗生素治疗的不完全依从可能会导致耐药性的产生，因为亚抑制浓度可能会刺激耐药突变体的选择。值得注意的是，最近的一项荟萃分析表明，药敏试验对于一线治疗的选择可能比二线或挽救治疗更有用。此外，荟萃分析和近期临床研究均表明，药敏指导治疗非常有效且优于经验性治疗。传统的药敏试验以培养和药敏试验为代表。然而，由于方法学相关因素，该方法并非在所有地方都可用，并且无法检测出异质性耐药。基于聚合酶链反应（PCR）的、无需培养的胃活检样本技术能够通过识别特定的点突变，准确地发现即使是极微量的基因型耐药菌株和异质性耐药状态。需要进行侵入性内镜检查一直是其推广的最重要限制因素。此外，进一步的进展是在粪便样本中检测细菌DNA中的点突变。与胃活检的培养或PCR相比，少数关于克拉霉素敏感性的研究显示出总体较高的敏感性和特异性。基于这些依据，现在有两种商业检测方法可用，尽管它们显示出一些有争议的结果。一种新型PCR方法在初步试验中显示组织和粪便结果完全一致。总之，尽管验证不足，但越来越多的证据表明，有可能获得能够检测抗生素耐药性的非侵入性检查方法。这类分析目前正处于非常早期的发展阶段，在其临床应用方面应谨慎。只有进一步旨在评估其敏感性和特异性的研究才能提供新的数据以供可靠参考。然而，非侵入性分子检测可能会提高患者的依从性、感染管理的时间/成本以及治疗效果。此外，由于大规模使用四联疗法以及患者依从性不完全而导致未来对四联疗法耐药性增加的潜在风险可以避免。
