腹腔脓肿治疗可以总结为 2 步:感染源控制和有效抗微生物药物疗法。感染源通常用手术或经皮式引流来控制,以完全引流脓肿腔。充足的感染源控制外加早期的适当有效抗菌疗法,通常已经足够。当瘘口较大无法封闭时,需要进一步手术以冲洗腹腔,控制感染源,通常的手术方式有修补瘘口或在瘘口近端拖出造口。值得注意的是,最初手术时感染未能控制可能会增加死亡率。[27]Barie PS, Williams MD, McCollam JS, et al; PROWESS Surgical Evaluation Committee. Benefit/risk profile of drotrecogin alfa (activated) in surgical patients with severe sepsis. Am J Surg. 2004;188:212-220.http://www.ncbi.nlm.nih.gov/pubmed/15450822?tool=bestpractice.com[28]Pieracci FM, Barie PS. Intra-abdominal infections. Curr Opin Crit Care. 2007;13:440-449.http://www.ncbi.nlm.nih.gov/pubmed/17599016?tool=bestpractice.com
根据严重程度和患者风险的分类
严重程度为轻度至中度的非高危状态定义为:[2]Solomkin JS, Mazuski JE, Bradley JS, et al. Diagnosis and management of complicated intra-abdominal infection in adults and children: guidelines by the Surgical Infection Society and the Infectious Diseases Society of America. Surg Infect (Larchmt). 2010;11:79-109.http://www.ncbi.nlm.nih.gov/pubmed/20163262?tool=bestpractice.com
高危或严重程度高定义为:[2]Solomkin JS, Mazuski JE, Bradley JS, et al. Diagnosis and management of complicated intra-abdominal infection in adults and children: guidelines by the Surgical Infection Society and the Infectious Diseases Society of America. Surg Infect (Larchmt). 2010;11:79-109.http://www.ncbi.nlm.nih.gov/pubmed/20163262?tool=bestpractice.com
经皮引流
经皮引流在大多数病例中是一种成功的模型。[6]Lagana D, Carrafiello G, Mangini M, et al. Image-guided percutaneous treatment of abdominal-pelvic abscesses: a 5-year experience. Radiol Med. 2008;113:999-1007.http://www.ncbi.nlm.nih.gov/pubmed/18795233?tool=bestpractice.com对于与疑似恶性肿瘤或大型吻合口瘘无关的简单脓肿,经皮引流若可用,应为一线治疗方法。经皮引流可在超声或 CT 引导下进行。[29]American College of Radiology. ACR appropriateness criteria: radiologic management of infected fluid collections. 2014. http://www.acr.org/ (last accessed 14 September 2017).https://acsearch.acr.org/docs/69345/Narrative/经皮引流对于仅有 1 处或 2 处腹腔脓肿的情况很有帮助,但当进入脓肿的通道会交叉污染其他诸如胸膜的腔时,或当感染源没有得到足分的控制,如大型吻合口破裂时,此法均受到限制。
经皮引流可以作为憩室炎、克罗恩病或阑尾炎分段式手术操作的一部分。[30]Andersen JC, Bundgaard L, Elbrønd H, et al; Danish Surgical Society. Danish national guidelines for treatment of diverticular disease. Dan Med J. 2012;59:C4453.http://www.danmedj.dk/portal/pls/portal/!PORTAL.wwpob_page.show?_docname=9020912.PDFhttp://www.ncbi.nlm.nih.gov/pubmed/22549495?tool=bestpractice.com采用经皮导管引流的分段式手术操作总体成功率约为 76%,在阑尾炎中达到 94%。[31]Cinat ME, Wilson SE, Din AM. Determinants for successful percutaneous image-guided drainage of intra-abdominal abscess. Arch Surg. 2002;137:845-849.http://archsurg.jamanetwork.com/article.aspx?articleid=212643http://www.ncbi.nlm.nih.gov/pubmed/12093344?tool=bestpractice.com通常用经皮引流处理阑尾脓肿,在多数病例中这是一种有效的疗法。对于克罗恩病相关脓肿,初步处理方法为抗生素和经皮引流,这样可以避免急诊手术和多次手术。在高度选择的病例中,可完全不需要手术。[32]Feagins LA, Holubar SD, Kane SV, et al. Current strategies in the management of intra-abdominal abscesses in Crohn's disease. Clin Gastroenterol Hepatol. 2011;9:842-850.http://www.cghjournal.org/article/S1542-3565(11)00451-4/fulltexthttp://www.ncbi.nlm.nih.gov/pubmed/21679776?tool=bestpractice.com
胰腺来源的脓肿或酵母培养阳性预示了不良结果,而术后脓肿则预示预后良好。[31]Cinat ME, Wilson SE, Din AM. Determinants for successful percutaneous image-guided drainage of intra-abdominal abscess. Arch Surg. 2002;137:845-849.http://archsurg.jamanetwork.com/article.aspx?articleid=212643http://www.ncbi.nlm.nih.gov/pubmed/12093344?tool=bestpractice.com开放性手术引流似乎死亡率更高,这是由于患者的选择偏倚所致。[11]Sirinek KR. Diagnosis and treatment of intra-abdominal abscesses. Surg Infect (Larchmt). 2000;1:31-38.http://www.ncbi.nlm.nih.gov/pubmed/12594907?tool=bestpractice.com在共计有 107 处脓肿的 95 名大型患者群中,分别进行了 71 例超声引导和 36 例 CT引导下的经皮引流。[6]Lagana D, Carrafiello G, Mangini M, et al. Image-guided percutaneous treatment of abdominal-pelvic abscesses: a 5-year experience. Radiol Med. 2008;113:999-1007.http://www.ncbi.nlm.nih.gov/pubmed/18795233?tool=bestpractice.com对 107 例积液使用 8F 至 14F 的猪尾巴导管引流全部成功,且未有重大并发症产生。总体来说,引流导管平均放置时间为 14.2 天。在 107 例中有 9 例的积液问题无法通过经皮引流解决。经皮式引流的危害性低于手术,但这种方法有它自己的缺点和并发症率。经皮引流并发症包括导管错位或堵塞、[6]Lagana D, Carrafiello G, Mangini M, et al. Image-guided percutaneous treatment of abdominal-pelvic abscesses: a 5-year experience. Radiol Med. 2008;113:999-1007.http://www.ncbi.nlm.nih.gov/pubmed/18795233?tool=bestpractice.com引流后败血症和引流不充分。其他并发症可能包括周围组织出血和意外损伤。
当临床症状消失且 24 小时内引流量<10 mL 时,可拔除导管。拔除导管之前,应确认引流停止不是因导管封闭而引起的。[25]Men S, Akhan O, Koroglu M. Percutaneous drainage of abdominal abcess. Eur J Radiol. 2002;43:204-218.http://www.ncbi.nlm.nih.gov/pubmed/12204403?tool=bestpractice.com
手术控制感染源
手术操作取决于腹腔脓肿的原因。在胃或十二指肠穿孔病例中,可通过格雷厄姆修补法去除覆盖物并引流来处理相关脓肿。小肠穿孔可能需要原位修补或切除,可通过原位吻合或双腔造口术来完成。憩室炎可能需要切除病变结肠,行末端结肠造口瘘术(Hartmann 手术)或一期吻合(行或不行改道回肠造口术)。[33]Oberkofler CE, Rickenbacher A, Raptis DA, et al. A multicenter randomized clinical trial of primary anastomosis or Hartmann's procedure for perforated left colonic diverticulitis with purulent or fecal peritonitis. Ann Surg. 2012;256:819-826.http://www.ncbi.nlm.nih.gov/pubmed/23095627?tool=bestpractice.com据报告,腹腔镜灌洗和引流对于化脓性腹膜炎患者也可行,但因试验的结果矛盾,因此存有争议。[34]Angenete E, Thornell A, Burcharth J, et al. Laparoscopic lavage is feasible and safe for the treatment of perforated diverticulitis with purulent peritonitis: the first results from the randomized controlled trial DILALA. Ann Surg. 2016;263:117-122.http://www.ncbi.nlm.nih.gov/pubmed/25489672?tool=bestpractice.com[35]Schultz JK, Yaqub S, Wallon C, et al. Laparoscopic lavage vs primary resection for acute perforated diverticulitis: the SCANDIV randomized clinical trial. JAMA. 2015;314:1364-1375.http://jama.jamanetwork.com/article.aspx?articleid=2449185http://www.ncbi.nlm.nih.gov/pubmed/26441181?tool=bestpractice.com[36]Thornell A, Angenete E, Bisgaard T, et al. Laparoscopic lavage for perforated diverticulitis with purulent peritonitis: a randomized trial. Ann Intern Med. 2016;164:137-145.http://www.ncbi.nlm.nih.gov/pubmed/26784672?tool=bestpractice.com 可通过近端改道和引流来治疗结肠吻合口瘘,无需切除吻合口。[37]Hedrick TL, Sawyer RG, Foley EF, et al. Anastomotic leak and the loop ileostomy: friend or foe? Dis Colon Rectum. 2006;49:1167-1176.http://www.ncbi.nlm.nih.gov/pubmed/16826334?tool=bestpractice.com当吻合口瘘发生时,临床处理主要是以下过程:先对脓毒性休克患者进行复苏,再明确瘘口是否可找到,将瘘口近端肠管拖出造口单次手术可能不足以充分控制感染源,可能需要二期或多期手术。血液动力学不稳定可能显示了肠连续性重建不当,通常需要在 24-48 小时内再次进行剖腹手术。若腹部仍处于开放状态,则可考虑创面负压治疗。[38]National Institute for Health and Care Excellence. Negative pressure wound therapy for the open abdomen. November 2013. http://www.nice.org.uk/ (last accessed 14 September 2017).http://www.nice.org.uk/guidance/ipg467在由胆源性脓毒症引起的化脓性肝脓肿中,应考虑同时行经皮或内镜下胆汁引流。通常通过经皮导管引流治疗包裹性肝脓肿。在多房性肝脓肿中,若经皮引流联合适当的抗生素治疗失败,可在剖腹手术前尝试将腹腔镜引流作为备选方案。[39]Aydin C, Piskin T, Sumer F, et al. Laparoscopic drainage of pyogenic liver abscess. JSLS. 2010;14(3):418-420.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3041043/http://www.ncbi.nlm.nih.gov/pubmed/21333200?tool=bestpractice.com
抗微生物药物治疗选择
早期肠外经验性抗菌疗法对治疗腹腔脓肿有重要意义。适当抗菌疗法的定义是,使用可以有效抵抗从腹腔脓肿分离得到的所有病原菌的抗生素。对于脓毒症或脓毒性休克患者,由于抗微生物疗法每延迟一小时临床结局就恶化一分,因此应在确诊后立即开始经验性静脉广谱抗生素治疗。[40]Kumar A, Roberts D, Wood KE, et al. Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock. Crit Care Med. 2006;34:1589-1596.http://www.ncbi.nlm.nih.gov/pubmed/16625125?tool=bestpractice.com在抗生素治疗开始之前应取样进行适当的微生物培养,但不能妨碍抗生素治疗的及时给药。[41]Dellinger RP, Levy MM, Rhodes A, et al. Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock, 2012. Intensive Care Med. 2013;39:165-228.http://link.springer.com/article/10.1007%2Fs00134-012-2769-8/fulltext.htmlhttp://www.ncbi.nlm.nih.gov/pubmed/23361625?tool=bestpractice.com在手术式或经皮引流之前应给予患者抗生素。
腹腔内感染的常见菌种在下面列出。
革兰阴性菌如大肠埃希氏菌、肠杆菌、克雷伯氏杆菌、变形杆菌或假单胞菌。
革兰阳性菌如链球菌、金黄色葡萄球菌或肠球菌。
厌氧菌如拟杆菌和梭菌最常见的腹腔内感染微生物是脆弱拟杆菌,占这些感染总数的三分之一到二分之一。
念珠菌。念珠菌感染的发生取决于免疫缺陷、先前抗菌治疗和腹膜透析这些诱发因素。更常见于在第三型腹膜炎(在第二型细菌性腹膜炎初步手术和抗菌疗法后发生的腹腔内感染复发)和十二指肠病理相关脓肿。
对这些病原体经验性覆盖的广度可能取决于疾病的严重程度、共病和对感染源控制的充分性。
外科感染协会 (SIS)[42]Mazuski JE, Sawyer RG, Nathens AB, et al. The Surgical Infection Society guidelines on antimicrobial therapy for intra-abdominal infections: evidence for the recommendations. Surg Infect (Larchmt). 2002;3:175-233.http://www.ncbi.nlm.nih.gov/pubmed/12542923?tool=bestpractice.com和美国传染病学会 (IDSA)[43]Solomkin JS, Mazuski JE, Baron EJ, et al. Guidelines for the selection of anti-infective agents for complicated intra-abdominal infections. Clin Infect Dis. 2003;37:997-1005.https://academic.oup.com/cid/article/37/8/997/436091/Guidelines-for-the-Selection-of-Anti-infectivehttp://www.ncbi.nlm.nih.gov/pubmed/14523762?tool=bestpractice.com均制定了复杂性腹腔内感染包括腹腔脓肿的抗菌治疗全国指南。有若干抗菌方法可用,但均未发现某一种效果更好。IDSA 建议是基于感染的严重程度给出的,而 SIS 的建议则是根据患者风险。这些建议被合并,且在 2010 年更新为新指南并发布。[2]Solomkin JS, Mazuski JE, Bradley JS, et al. Diagnosis and management of complicated intra-abdominal infection in adults and children: guidelines by the Surgical Infection Society and the Infectious Diseases Society of America. Surg Infect (Larchmt). 2010;11:79-109.http://www.ncbi.nlm.nih.gov/pubmed/20163262?tool=bestpractice.com这些指南根据感染的严重程度和医疗条件背景给出治疗建议。值得注意的是,一篇大型 Cochrane 综述对继发性腹膜炎的一线抗生素治疗方案并无具体建议,这些方案均有不错的疗效。[44]Wong PF, Gilliam AD, Kumar S, et al. Antibiotic regimens for secondary peritonitis of gastrointestinal origin in adults. Cochrane Database Syst Rev. 2005;(2):CD004539.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD004539.pub2/fullhttp://www.ncbi.nlm.nih.gov/pubmed/15846719?tool=bestpractice.com
可通过单药治疗(如厄他培南或莫西沙星)或联合方案(如甲硝唑联合头孢菌素或喹诺方案)治疗轻度到中度社区获得性 IAA 非高风险患者,这些方案的疗效相同。[2]Solomkin JS, Mazuski JE, Bradley JS, et al. Diagnosis and management of complicated intra-abdominal infection in adults and children: guidelines by the Surgical Infection Society and the Infectious Diseases Society of America. Surg Infect (Larchmt). 2010;11:79-109.http://www.ncbi.nlm.nih.gov/pubmed/20163262?tool=bestpractice.com经验抗生素应覆盖革兰阴性需氧菌、兼性厌氧菌和肠道革兰阳性链球菌。在出现伴有梗阻或麻痹性肠梗阻的末端回肠、阑尾、结肠和胃肠近端的穿孔情况下,这些抗生素对专性厌氧菌有效。[2]Solomkin JS, Mazuski JE, Bradley JS, et al. Diagnosis and management of complicated intra-abdominal infection in adults and children: guidelines by the Surgical Infection Society and the Infectious Diseases Society of America. Surg Infect (Larchmt). 2010;11:79-109.http://www.ncbi.nlm.nih.gov/pubmed/20163262?tool=bestpractice.com这些患者中,不推荐覆盖肠球菌和念珠菌的经验性抗生素治疗[2]Solomkin JS, Mazuski JE, Bradley JS, et al. Diagnosis and management of complicated intra-abdominal infection in adults and children: guidelines by the Surgical Infection Society and the Infectious Diseases Society of America. Surg Infect (Larchmt). 2010;11:79-109.http://www.ncbi.nlm.nih.gov/pubmed/20163262?tool=bestpractice.com。不应使用氨苄西林-舒巴坦、头孢替坦和克林霉素,因为大肠埃希菌和脆弱拟杆菌分别对前述抗生素耐药。[2]Solomkin JS, Mazuski JE, Bradley JS, et al. Diagnosis and management of complicated intra-abdominal infection in adults and children: guidelines by the Surgical Infection Society and the Infectious Diseases Society of America. Surg Infect (Larchmt). 2010;11:79-109.http://www.ncbi.nlm.nih.gov/pubmed/20163262?tool=bestpractice.com患者可在获得培养结果后立刻转换为针对性的抗生素治疗。
高危或患严重社区获得性腹腔脓肿的患者,应启用广谱抗菌疗法以覆盖可能存在的多药物耐药性革兰阴性菌,包括铜绿假单胞菌,一旦培养和药敏结果可用,则缩小抗菌谱。关于最佳抗菌疗法的具体决策,某种程度上应取决于地方抗菌谱,以及对医院或社区常见微生物的了解。碳青霉烯类或哌拉西林/他唑巴坦应作为单药治疗使用;若需要联合,应将甲硝唑与头孢菌素联合。[2]Solomkin JS, Mazuski JE, Bradley JS, et al. Diagnosis and management of complicated intra-abdominal infection in adults and children: guidelines by the Surgical Infection Society and the Infectious Diseases Society of America. Surg Infect (Larchmt). 2010;11:79-109.http://www.ncbi.nlm.nih.gov/pubmed/20163262?tool=bestpractice.com对于这些患者,应考虑经验性的覆盖肠球菌。只在有耐甲氧西林金黄色葡萄球菌 (MRSA) 和念珠菌感染证据时,才建议覆盖这些菌株。[2]Solomkin JS, Mazuski JE, Bradley JS, et al. Diagnosis and management of complicated intra-abdominal infection in adults and children: guidelines by the Surgical Infection Society and the Infectious Diseases Society of America. Surg Infect (Larchmt). 2010;11:79-109.http://www.ncbi.nlm.nih.gov/pubmed/20163262?tool=bestpractice.com
在院内感染的复杂性腹腔内感染患者中,为依据经验覆盖可能的病原菌,应使用多药方案,其中包括对革兰阴性需氧菌和兼性厌氧菌有作用的广谱药物。[2]Solomkin JS, Mazuski JE, Bradley JS, et al. Diagnosis and management of complicated intra-abdominal infection in adults and children: guidelines by the Surgical Infection Society and the Infectious Diseases Society of America. Surg Infect (Larchmt). 2010;11:79-109.http://www.ncbi.nlm.nih.gov/pubmed/20163262?tool=bestpractice.com建议将碳青霉烯类、哌拉西林/他唑巴坦、头孢菌素或氨基糖苷和甲硝唑共同使用。建议使用针对粪肠球菌的经验性抗肠球菌疗法(如哌拉西林/他唑巴坦),尤其是术后感染的患者或植入血管内假体材料的患者、曾接受头孢菌素或其他抗肠球菌抗生素治疗的患者,以及免疫功能受损患者。[2]Solomkin JS, Mazuski JE, Bradley JS, et al. Diagnosis and management of complicated intra-abdominal infection in adults and children: guidelines by the Surgical Infection Society and the Infectious Diseases Society of America. Surg Infect (Larchmt). 2010;11:79-109.http://www.ncbi.nlm.nih.gov/pubmed/20163262?tool=bestpractice.com
多重耐药病原体正成为一个越来越受到关注的问题。抗万古霉素肠球菌属 (VRE) 是新出现的对多种标准抗生素耐药的病原菌。特定抗菌剂的疗效和安全性数据有限,有关腹腔内感染治疗方面的数据更少。利奈唑胺已被批准用于治疗抗万古霉素肠球菌属的感染,也可使用替加环素。其他抗菌剂已开始被使用,但尚未被批准。[45]Birmingham MC, Rayner CR, Meagher AK, et al. Linezolid for the treatment of multidrug-resistant, gram-positive infections: experience from a compassionate-use program. Clin Infect Dis. 2003;36:159-168.http://cid.oxfordjournals.org/content/36/2/159.longhttp://www.ncbi.nlm.nih.gov/pubmed/12522747?tool=bestpractice.com[46]Rivera AM, Boucher HW. Current concepts in antimicrobial therapy against select gram-positive organisms: methicillin-resistant Staphylococcus aureus, penicillin-resistant pneumococci, and vancomycin-resistant enterococci. Mayo Clin Proc. 2011;86:1230-1243.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3228624/http://www.ncbi.nlm.nih.gov/pubmed/22134942?tool=bestpractice.com[47]Rubinstein E, Keynan Y. Vancomycin-resistant enterococci. Crit Care Clin. 2013;29:841-852.http://www.ncbi.nlm.nih.gov/pubmed/24094380?tool=bestpractice.com对于因治疗失败或大量抗生素暴露导致耐甲氧西林金黄色葡萄球菌感染风险高,或携带耐甲氧西林金黄色葡萄球菌的患者,可使用辅助性万古霉素覆盖。[2]Solomkin JS, Mazuski JE, Bradley JS, et al. Diagnosis and management of complicated intra-abdominal infection in adults and children: guidelines by the Surgical Infection Society and the Infectious Diseases Society of America. Surg Infect (Larchmt). 2010;11:79-109.http://www.ncbi.nlm.nih.gov/pubmed/20163262?tool=bestpractice.com其他多重耐药微生物包括产超广谱β-内酰胺酶 (ESBL) 的革兰氏阴性杆菌。碳青霉烯类药物是治疗 ESBL 细菌的一线选择,厄他培南可能是社区获得性感染的首选治疗。[48]Delgado-Valverde M, Sojo-Dorado J, Pascual A, et al. Clinical management of infections caused by multi-drug resistant Enterobacteriaceae. Ther Adv Infect Dis. 2013;1:49-69.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4040721/http://www.ncbi.nlm.nih.gov/pubmed/25165544?tool=bestpractice.com也可进行其他选择,具体取决于菌株的敏感性。由于出现耐碳青霉烯类抗生素的肠杆菌 (CRE),因此开发新的药物很重要。治疗的选择包括但不局限于粘菌素甲磺酸(粘菌素)和替加环素。头孢他啶/阿维巴坦 (avibactam) 已在包括美国等的一些国家获准与甲硝唑联合用于治疗复杂腹腔内感染。头孢他啶/阿维巴坦的有效性与碳青酶烯类药物相似。阿维巴坦的成分可增强头孢他啶对抗 β 内酰胺酶革兰氏阴性菌的活性。[49]Zhanel GG, Lawson CD, Adam H, et al. Ceftazidime-avibactam: a novel cephalosporin/beta-lactamase inhibitor combination. Drugs. 2013;73:159-177.http://www.ncbi.nlm.nih.gov/pubmed/23371303?tool=bestpractice.com但是需要进一步试验。[50]Pitart C, Marco F, Keating TA, et al. Evaluation of the activity of ceftazidime-avibactam against fluoroquinolone-resistant Enterobacteriaceae and Pseudomonas. Antimicrob Agents Chemother. 2015;59:3059-3065.http://www.ncbi.nlm.nih.gov/pubmed/25753646?tool=bestpractice.com只有当腹腔内感染物质培养出念珠菌时,才建议使用抗真菌治疗。应使用氟康唑治疗白念珠菌,而棘球白素应用于治疗氟康唑耐药的念珠菌及危重患者。[2]Solomkin JS, Mazuski JE, Bradley JS, et al. Diagnosis and management of complicated intra-abdominal infection in adults and children: guidelines by the Surgical Infection Society and the Infectious Diseases Society of America. Surg Infect (Larchmt). 2010;11:79-109.http://www.ncbi.nlm.nih.gov/pubmed/20163262?tool=bestpractice.com
抗微生物药物疗法的持续时间
抗菌疗法的疗程取决于感染源控制的充分性,以及患者对于治疗的反应(所有感染的症状、体征如发热、白细胞增多、腹痛和腹腔脓肿消退)若患者对于经验广谱抗菌疗法没有反应,应反复进行影像学诊断和细菌培养,并且考虑更换抗生素。若患者有菌血症,建议进行为期 2 周的抗菌疗法。
一项抗微生物药物治疗持续时间更短的成功试验凸显了感染源控制的重要性。一项多中心 SIS 随机试验针对复杂腹腔内感染比较了两种抗微生物药物治疗持续时间,一种是根据感染临床体征和症状消退情况选择药物,另一种是在感染源控制后用药 4 天。这项研究发现,接受 4 天抗微生物药物治疗的患者治疗期较短,在手术部位感染,复发性腹腔感染和 30 天内死亡等复合临床结局方面没有差异。[51]Sawyer RG, Claridge JA, Nathens AB, et al. Trial of short-course antimicrobial therapy for intraabdominal infection. N Engl J Med. 2015;372:1996-2005.http://www.nejm.org/doi/full/10.1056/NEJMoa1411162#t=articlehttp://www.ncbi.nlm.nih.gov/pubmed/25992746?tool=bestpractice.com