Biswas Dr Pritam, Tk Dr Sukumar
Department of Medical Pharmacology & Clinical Therapeutics, St Matthews University School of Medicine, Georgetown, Grand Cayman, Cayman Islands.
Department of Medical Microbiology & Immunology, St Matthews University School of Medicine, Georgetown, Grand Cayman, Cayman Islands.
Clin Res Hepatol Gastroenterol. 2022 Mar;46(3):101832. doi: 10.1016/j.clinre.2021.101832. Epub 2021 Nov 12.
Biofilm-producing bacteria are relatively resistant to antibiotics, as the penetration of antibiotics into the endopolysaccharide envelope is incomplete. N Acetyl cysteine (NAC) is known to destabilize the biofilms, as it cleaves the disulfide bonds of mucus glycoproteins, reducing the viscosity and thickness of mucus. This allows NAC to act synergistically with antibiotics for the eradication of H Pylori. The meta-analysis evaluates the evidence of the efficacy of adjuvant N acetyl cysteine (NAC) compared to standard therapies in the eradication of H. Pylori infections.
We searched randomized clinical trials in MEDLINE, Cochrane Central Register of Clinical Trials (CENTRAL), EBSCO, Database of Abstracts of Reviews of Effects (DARE), and Google Scholar. We included trials comparing standard treatment protocols plus adjuvant NAC and the same regimen without NAC. These studies included adults with a diagnosis of Helicobacter pylori infection. Our primary outcome was the successful eradication of H. Pylori. The results were pooled using a random-effects model, and data were analyzed using RevMan 5.0 software. Cochrane collaboration's tool was used to assess the risk of bias. Publication bias and other inconsistencies were assessed. Sensitivity analyses and grading of evidence were performed.
Eight studies, comprising 1167 patients, were included in the meta-analysis, the pooled outcomes of patients on adjuvant NAC+ standard eradication therapy noted an eradication rate of 76.1% (n=581) compared to the patients in standard eradication therapy with a rate of 72.18% (n=586), RR 1.17 [95% CI (0.99, 1.39); I2= 64%; p value=0.07]. Moderate to severe heterogeneity was noted. These pooled results show that adjuvant NAC plus standard treatment protocols are not superior to standard treatment protocols for H pylori eradication. Similar results were seen in the use of adjuvant NAC with 'currently used standard treatment protocols' (78.3% versus 76.3%, RR 1.08, [95% CI 0.94 to 1.25]; I2=55%; p=0.28; n= 829 patients], as well as in the treatment of naïve patients (79.8% versus 80.9%, RR 1.00[95% CI 0.87 to 1.15]; i2=27%; P=-0.98; n= 775 patients].
Adjuvant NAC plus standard treatment protocols are not superior to standard treatment protocols for H. pylori eradication. These findings are consistent with the use of adjuvant NAC with 'currently used standard treatment protocols' (clarithromycin-based triple therapies) and also with adjuvant NAC used in the treatment of naïve patients. We are moderately certain of these findings. Future studies could explore the use of NAC as a pretreatment before using the current standard therapies in the eradication of H. Pylori rather than NAC as adjuvant therapy.
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产生生物膜的细菌对抗生素相对耐药，因为抗生素向内多糖包膜的渗透不完全。已知N-乙酰半胱氨酸（NAC）可破坏生物膜的稳定性，因为它能裂解黏液糖蛋白的二硫键，降低黏液的黏度和厚度。这使得NAC能够与抗生素协同作用以根除幽门螺杆菌。本荟萃分析评估了与标准疗法相比，辅助使用N-乙酰半胱氨酸（NAC）根除幽门螺杆菌感染疗效的证据。
我们在医学文献数据库（MEDLINE）、考克兰系统评价数据库（CENTRAL）、EBSCO、循证医学数据库（DARE）和谷歌学术中检索随机临床试验。我们纳入了比较标准治疗方案加辅助NAC与不含NAC的相同治疗方案的试验。这些研究纳入了诊断为幽门螺杆菌感染的成年人。我们的主要结局是成功根除幽门螺杆菌。使用随机效应模型汇总结果，并使用RevMan 5.0软件分析数据。采用考克兰协作工具评估偏倚风险。评估发表偏倚和其他不一致性。进行敏感性分析和证据分级。
八项研究共1167例患者纳入荟萃分析，辅助NAC+标准根除治疗患者的汇总结局显示根除率为76.1%（n = 581），而标准根除治疗患者的根除率为72.18%（n = 586），风险比为1.17 [95%置信区间（0.99，1.39）；I² = 64%；p值 = 0.07]。观察到中度至重度异质性。这些汇总结果表明，辅助NAC加标准治疗方案在根除幽门螺杆菌方面并不优于标准治疗方案。在使用辅助NAC与“当前使用的标准治疗方案”时也观察到类似结果（78.3%对76.3%，风险比1.08，[95%置信区间0.94至1.25]；I² = 55%；p = 0.28；n = 829例患者），以及在初治患者的治疗中（79.8%对80.9%，风险比1.00[95%置信区间0.87至1.15]；I² = 27%；P = -0.98；n = 775例患者）。
辅助NAC加标准治疗方案在根除幽门螺杆菌方面并不优于标准治疗方案。这些发现与使用辅助NAC与“当前使用的标准治疗方案”（基于克拉霉素的三联疗法）一致，也与在初治患者治疗中使用辅助NAC一致。我们对这些发现有中等程度的把握。未来的研究可以探索在使用当前标准疗法根除幽门螺杆菌之前将NAC用作预处理，而不是将NAC用作辅助疗法。
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