腹水低蛋白浓度(<15 g/L[<1.5 g/dL])是 SBP 的一个危险因素。研究发现,这些患者预防性口服抗生素可减少首次 SBP 的发生降低腹水低蛋白患者的初次自发性细菌性腹膜炎 (SBP) 发生率:有高质量的研究证据表明预防性口服抗生素可减少腹水低蛋白浓度(<15 g/L[<1.5 g/dL])患者的初次 SBP 发生率。[6]Blaise M, Pateron D, Trinchet JC, et al. Systemic antibiotic therapy prevents bacterial infections in cirrhotic patients presenting with gastrointestinal hemorrhage. Hepatology. 1994;20:34-38.http://www.ncbi.nlm.nih.gov/pubmed/8020902?tool=bestpractice.com[52]Loomba R, Wesley R, Bain A, et al. Role of fluoroquinolones in the primary prophylaxis of spontaneous bacterial peritonitis: meta-analysis. Clin Gastroenterol Hepatol. 2009;7:487-493.http://www.ncbi.nlm.nih.gov/pubmed/19250986?tool=bestpractice.com[53]Fernandez J, Navasa M, Planas R, et al. Primary prophylaxis of spontaneous bacterial peritonitis delays hepatorenal syndrome and improves survival in cirrhosis. Gastroenterology. 2007;133:818-824.http://www.ncbi.nlm.nih.gov/pubmed/17854593?tool=bestpractice.com[54]Pauwels A, Mostefa-Kara N, Debenes B, et al. Systemic antibiotic prophylaxis after gastrointestinal hemorrhage in cirrhotic patients with a high risk of infection. Hepatology. 1996;24:802-806.http://www.ncbi.nlm.nih.gov/pubmed/8855179?tool=bestpractice.com[55]Hsieh WJ, Lin HC, Hwang SJ, et al. The effect of ciprofloxacin in the prevention of bacterial infection in patients with cirrhosis after upper gastrointestinal bleeding. Am J Gastroenterol. 1998;93:962-966.http://www.ncbi.nlm.nih.gov/pubmed/9647029?tool=bestpractice.com[56]Saab S, Hernandez JC, Chi AC, et al. Oral antibiotic prophylaxis reduces spontaneous bacterial peritonitis occurrence and improves short-term survival in cirrhosis: a meta-analysis. Am J Gastroenterol. 2009;104:993-1001.http://www.ncbi.nlm.nih.gov/pubmed/19277033?tool=bestpractice.com一个 meta 分析发现其可降低 8%SBP 风险,这意味着 13 个治疗患者可防止 1 个患者出现 SBP。系统评价或者受试者>200名的随机对照临床试验(RCT)。和其他细菌感染并减少病死率。降低低腹水蛋白患者的病死率:有高质量的研究证据表明预防性口服抗生素可提高 1 年生存率(60%,未治疗的患者为 48%)。[52]Loomba R, Wesley R, Bain A, et al. Role of fluoroquinolones in the primary prophylaxis of spontaneous bacterial peritonitis: meta-analysis. Clin Gastroenterol Hepatol. 2009;7:487-493.http://www.ncbi.nlm.nih.gov/pubmed/19250986?tool=bestpractice.com[53]Fernandez J, Navasa M, Planas R, et al. Primary prophylaxis of spontaneous bacterial peritonitis delays hepatorenal syndrome and improves survival in cirrhosis. Gastroenterology. 2007;133:818-824.http://www.ncbi.nlm.nih.gov/pubmed/17854593?tool=bestpractice.commeta 分析发现一个明显的短期效果(证据来自一个关于一级预防和二级预防 2 组患者的高质量研究),治疗的患者 3 个月病死率为 6%,未经治疗的患者为 22%。[56]Saab S, Hernandez JC, Chi AC, et al. Oral antibiotic prophylaxis reduces spontaneous bacterial peritonitis occurrence and improves short-term survival in cirrhosis: a meta-analysis. Am J Gastroenterol. 2009;104:993-1001.http://www.ncbi.nlm.nih.gov/pubmed/19277033?tool=bestpractice.com系统评价或者受试者>200名的随机对照临床试验(RCT)。系统性评价回顾了不同研究方法的多项研究。一项研究比较了腹水低蛋白浓度(<15 g/L[<1.5 g/dL])加上另外一个 SBP 的危险因素(肝衰竭晚期、肾功能不全或血钠水平≤130 mmol/L)患者预防性使用抗生素的益处。被随机分到每日口服诺氟沙星组的患者与安慰剂组相比,SBP 的发生率降低(7% 比 61%),肝肾综合征的发生率降低(28% 比 41%),3 个月和 12 个月的病死率亦降低(6% 比 38%,40% 比 52%)。[53]Fernandez J, Navasa M, Planas R, et al. Primary prophylaxis of spontaneous bacterial peritonitis delays hepatorenal syndrome and improves survival in cirrhosis. Gastroenterology. 2007;133:818-824.http://www.ncbi.nlm.nih.gov/pubmed/17854593?tool=bestpractice.com虽然大部分研究都是使用已在某些国家/地区(包括美国)停用的诺氟沙星进行的,但使用环丙沙星和甲氧苄啶/磺胺甲噁唑的预防性治疗也已显示出益处。 [
]What are the benefits and harms of antibiotic prophylaxis for spontaneous bacterial peritonitis in cirrhotic patients?http://cochraneclinicalanswers.com/doi/10.1002/cca.537/full显示答案
抗生素预防性治疗益处必须权衡长期应用抗生素的风险。研究发现,没有全面评估长期应用抗生素的风险可出现一些危害,如患者和社区患者尿道或腹水出现耐氟喹诺酮类病原体,出现氟喹诺酮类药物的肌肉骨骼副作用和难辨梭菌感染。[57]Cohen MJ, Sahar T, Benenson S, et al. Antibiotic prophylaxis for spontaneous bacterial peritonitis in cirrhotic patients with ascites, without gastro-intestinal bleeding. Cochrane Database Syst Rev. 2009;(2):CD004791.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD004791.pub2/fullhttp://www.ncbi.nlm.nih.gov/pubmed/19370611?tool=bestpractice.com[58]Segarra-Newnham M, Henneman A. Antibiotic prophylaxis for prevention of spontaneous bacterial peritonitis in patients without gastrointestinal bleeding. Ann Pharmacother. 2010;44:1946-1954.http://www.ncbi.nlm.nih.gov/pubmed/21098755?tool=bestpractice.com
利福昔明是一种口服吸收差的广谱抗生素,研究发现其可作为 SBP 的一级预防药物。一小型观察性研究表明,口服利福昔明可减少腹水中性粒细胞计数及降低血浆内毒素水平。[59]Kalambokis GN, Mouzaki A, Rodi M, et al. Rifaximin for the prevention of spontaneous bacterial peritonitis. World J Gastroenterol. 2012;18:1700-1702.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3325539/http://www.ncbi.nlm.nih.gov/pubmed/22529702?tool=bestpractice.com
3 项随机对照试验的 meta 分析表明,β受体阻滞剂可预防肝硬化和腹水患者 SBP 的发生。这 3 项研究使用了普萘洛尔和纳多洛尔(2 项试验用于二级预防、1 项试验用于一级预防)。[60]Senzolo M, Cholongitas E, Burra P, et al. beta-Blockers protect against spontaneous bacterial peritonitis in cirrhotic patients: a meta-analysis. Liver Int. 2009;29:1189-1193.http://www.ncbi.nlm.nih.gov/pubmed/19508620?tool=bestpractice.com一个随机对照试验表明,在诺氟沙星基础上加用益生菌后并没有增加疗效。[61]Pande C, Kumar A, Sarin SK. Addition of probiotics to norfloxacin does not improve efficacy in the prevention of spontaneous bacterial peritonitis: a double-blind placebo-controlled randomized-controlled trial. Eur J Gastroenterol Hepatol. 2012;24:831-839.http://www.ncbi.nlm.nih.gov/pubmed/22522141?tool=bestpractice.com
质子泵抑制剂 (PPIs) 可促进肠道细菌定植、过度生长并易位至腹腔,可能增加 SBP 的风险。一个 4 项临床相关研究的 meta 分析显示,使用 PPI 和 SBP 的发生有显著重要关联。[62]Trikudanathan G, Israel J, Cappa J, et al. Association between proton-pump inhibitors and spontaneous bacterial peritonitis in cirrhotic patients - a systematic review and meta-analysis. Int J Clin Pract. 2011;65:674-678.http://www.ncbi.nlm.nih.gov/pubmed/21564440?tool=bestpractice.com但其他研究没有发现 PPI 的使用与 SBP 存在正相关。[63]Campbell MS, Obstein K, Reddy KR, et al. Association between proton pump inhibitor use and spontaneous bacterial peritonitis. Dig Dis Sci. 2008;53:394-398.http://rd.springer.com/article/10.1007/s10620-007-9899-9/fulltext.htmlhttp://www.ncbi.nlm.nih.gov/pubmed/17616817?tool=bestpractice.com[64]Terg R, Casciato P, Garbe C, et al; Study Group of Cirrhosis Complications of the Argentine Association for the Study of Liver Disease. Proton pump inhibitor therapy does not increase the incidence of spontaneous bacterial peritonitis in cirrhosis: a multicenter prospective study. J Hepatol. 2015;62:1056-1060.http://www.ncbi.nlm.nih.gov/pubmed/25481567?tool=bestpractice.com鉴于这些有矛盾的数据,在决定对肝硬化患者处方 PPI 时,应当谨慎。