所有疑似为脑膜炎球菌感染的患者应被隔离在单独的房间,并采取防护措施。对于任何疑似患有脑膜炎球菌感染的患者,在可行情况下应尽快开始抗菌治疗。该治疗会降低 LP 诊断率,但若无法快速完成诊断性评估则不可延迟抗生素治疗。因为脑膜炎球菌感染无法快速与其他细菌性病原体导致的严重感染进行区分,因此经验性抗菌治疗应包括涉及肺炎链球菌与金黄色葡萄球菌的广谱类药物。 [
]In suspected cases of meningococcal disease, do pre-admission antibiotics improve outcomes?http://cochraneclinicalanswers.com/doi/10.1002/cca.99/full显示答案
针对疑似脑膜炎的经验经抗菌治疗
初始抗生素选择取决于年龄:[36]Tunkel AR, Hartman BJ, Kaplan SL, et al. Practice guidelines for the management of bacterial meningitis. Clin Infect Dis. 2004;39:1267-1284.https://academic.oup.com/cid/article/39/9/1267/402080/Practice-Guidelines-for-the-Management-ofhttp://www.ncbi.nlm.nih.gov/pubmed/15494903?tool=bestpractice.com[40]Therapy for children with invasive pneumococcal infections. American Academy of Pediatrics Committee on Infectious Diseases. Pediatrics. 1997;99:289-299.http://pediatrics.aappublications.org/cgi/content/full/99/2/289http://www.ncbi.nlm.nih.gov/pubmed/9024464?tool=bestpractice.com[41]National Institute for Health and Care Excellence. Meningitis (bacterial) and meningococcal septicaemia in under 16s: recognition, diagnosis and management. June 2015. http://guidance.nice.org.uk (last accessed 10 March 2017).http://www.nice.org.uk/guidance/CG102/chapter/introduction[42]De Gaudio M, Chiappini E, Galli L, et al. Therapeutic management of bacterial meningitis in children: a systematic review and comparison of published guidelines from a European perspective. J Chemother. 2010;22:226-237.http://www.ncbi.nlm.nih.gov/pubmed/20685625?tool=bestpractice.com[43]European Centre for Disease Prevention and Control (ECDC). Public health management of sporadic cases of invasive meningococcal disease and their contacts. October 2010. http://ecdc.europa.eu (last accessed 10 March 2017).http://ecdc.europa.eu/en/publications/Publications/1010_GUI_Meningococcal_guidance.pdf[44]Visintin C, Mugglestone MA, Fields EJ, et al. Management of bacterial meningitis and meningococcal septicaemia in children and young people: summary of NICE guidance. BMJ. 2010;340:c3209.http://www.ncbi.nlm.nih.gov/pubmed/20584794?tool=bestpractice.com
年龄小于 1 个月的儿童:头孢噻肟或头孢曲松+氨苄西林
1 个月至 50 岁:头孢噻肟或头孢曲松或头孢吡肟+万古霉素
>50 岁或免疫功能受损的患者:氨苄西林加头孢噻肟或头孢曲松或头孢吡肟+万古霉素
在头孢曲松抗药性并未广泛存在的地区(如巴西),不可常规使用万古霉素。
辅助疗法:
一些研究已经表明,高剂量皮质类固醇会减少神经系统后遗症的可能性,尤其是在肺炎球菌病中;但在脑膜炎球菌性脑膜炎中,辅助性皮质类固醇的作用仍有争议[36]Tunkel AR, Hartman BJ, Kaplan SL, et al. Practice guidelines for the management of bacterial meningitis. Clin Infect Dis. 2004;39:1267-1284.https://academic.oup.com/cid/article/39/9/1267/402080/Practice-Guidelines-for-the-Management-ofhttp://www.ncbi.nlm.nih.gov/pubmed/15494903?tool=bestpractice.com[45]Brouwer MC, McIntyre P, Prasad K, et al. Corticosteroids for acute bacterial meningitis. Cochrane Database Syst Rev. 2015;(9):CD004405.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD004405.pub5/fullhttp://www.ncbi.nlm.nih.gov/pubmed/26362566?tool=bestpractice.com[46]van de Beek D, Farrar JJ, de Gans J, et al. Adjunctive dexamethasone in bacterial meningitis: a meta-analysis of individual patient data. Lancet Neurol. 2010;9:254-263.http://www.ncbi.nlm.nih.gov/pubmed/20138011?tool=bestpractice.com在脑膜炎奈瑟菌导致的脑膜炎中,辅助性皮质类固醇治疗总体上没有使死亡率显著降低,在儿童中,它没有减少重度听力受损。[45]Brouwer MC, McIntyre P, Prasad K, et al. Corticosteroids for acute bacterial meningitis. Cochrane Database Syst Rev. 2015;(9):CD004405.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD004405.pub5/fullhttp://www.ncbi.nlm.nih.gov/pubmed/26362566?tool=bestpractice.com
对于疑似细菌性脓毒症,大多数专家建议:年龄大于 1 个月非免疫功能低下的患者接受持续 2 至 4 天的地塞米松,首次给药早于或同时于抗菌药物的首次给药。 [
]In children with acute bacterial meningitis, is there randomized controlled trial evidence to support adding corticosteroids to standard treatment with antibacterial agents?http://cochraneclinicalanswers.com/doi/10.1002/cca.1217/full显示答案 [
]In adults with acute bacterial meningitis, is adding corticosteroids to standard treatment with antibacterial agents helpful?http://cochraneclinicalanswers.com/doi/10.1002/cca.1273/full显示答案 若细菌性脓毒症诊断被推翻,则应终止皮质类固醇用药。[36]Tunkel AR, Hartman BJ, Kaplan SL, et al. Practice guidelines for the management of bacterial meningitis. Clin Infect Dis. 2004;39:1267-1284.https://academic.oup.com/cid/article/39/9/1267/402080/Practice-Guidelines-for-the-Management-ofhttp://www.ncbi.nlm.nih.gov/pubmed/15494903?tool=bestpractice.com
针对疑似脑膜炎球菌性菌血症的经验性抗菌治疗
针对疑似脑膜炎球菌性菌血症患者的经验性治疗选择应以当地易感模式为基础,但通常情况包括:[47]Gilbert DN, Moellering RC, Eliopoulos GM, et al. The Sanford guide to antimicrobial therapy 2013. 43rd ed. Sperryville, VA: Antimicrobial Therapy, Inc; 2013.
年龄< 1 个月的儿童:头孢噻肟或头孢曲松或一种氨基糖苷类药物+氨苄西林。阿昔洛韦适用于有疾病表现、黏膜皮肤囊泡、癫痫发作或脑脊液细胞增多的婴儿
年龄≥大于 1 个月的儿童:头孢噻肟或头孢曲松或头孢吡肟+万古霉素
成人:万古霉素+头孢曲松或头孢噻肟或头孢吡肟或亚胺培南/西司他丁或美罗培南+/-庆大霉素或妥布霉素或阿米卡星
在头孢曲松抗药性并未广泛存在的地区(如巴西),不可常规使用万古霉素。
疑似菌血症的管理越来越复杂,其管理应以当地微生物学、危险因素(如,免疫功能受损状态、局灶性感染)及疾病严重程度为基础。
支持疗法
支持疗法的主要目标为:恢复并维持正常的呼吸、心脏及神经功能。脑膜炎球菌感染可快速进展,即使及时给予了抗生素治疗,临床恶化仍可持续。初始评估应遵循儿科及成人高级生命支持的原则,对患者气道、呼吸及循环状态进行评估,并确立静脉内大直径导管的液体给药方式,以保证安全给药。[35]Nadel S, Kroll JS. Diagnosis and management of meningococcal disease: the need for centralized care. FEMS Microbiol Rev. 2007;31:71-83.http://onlinelibrary.wiley.com/doi/10.1111/j.1574-6976.2006.00059.x/fullhttp://www.ncbi.nlm.nih.gov/pubmed/17233636?tool=bestpractice.com[48]Dellinger RP, Levy MM, Rhodes A, et al. Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock, 2012. Crit Care Med. 2013;41:580-637.http://www.sccm.org/Documents/SSC-Guidelines.pdfhttp://www.ncbi.nlm.nih.gov/pubmed/23353941?tool=bestpractice.com
具有代偿性休克症状或呼吸窘迫的患者应接受辅助供氧,而存在非代偿性休克、缺氧、重度呼吸窘迫、意识障碍或颅内压升高证据的人需进行插管及机械性呼吸。在对液体复苏无即刻反应的低血压或灌注不良患者中,应进行血管加压药(肾上腺素[epinephrine]、去甲肾上腺素[norepinephrine]、米力农、多巴胺)用药。在有证据表明存在颅内压升高、心肌功能异常或急性呼吸窘迫综合征 (ARDS) 的患者中,液体类用药应谨慎。
确诊脑膜炎的治疗
一旦脑膜炎球菌感染确诊(通常在住院后 12-48 小时内),则为患者提供针对确诊脑膜炎球菌感染的治疗:如有必要,将患者的抗微生物药物治疗改为第三代头孢菌素静脉用药或其他确定性治疗,以及给予地塞米松,如果已经使用地塞米松,继续治疗,总共持续 2 至 4 天。[36]Tunkel AR, Hartman BJ, Kaplan SL, et al. Practice guidelines for the management of bacterial meningitis. Clin Infect Dis. 2004;39:1267-1284.https://academic.oup.com/cid/article/39/9/1267/402080/Practice-Guidelines-for-the-Management-ofhttp://www.ncbi.nlm.nih.gov/pubmed/15494903?tool=bestpractice.com确诊脑膜炎球菌感染的首选治疗药物为:静脉内使用头孢曲松、头孢噻肟或头孢吡肟,连续 5-7 天。替代药物包括苄基青霉素(用于青霉素最低抑菌浓度<0.1 μg/mL 的菌株)、氨苄西林、美罗培南、氯霉素,或在成人中,使用氟喹诺酮类药物。药物选择取决于患者的个体情况、抗微生物药物敏感性及当地药物可获得情况。 [
]How do third generation cephalosporins compare with conventional antibiotics at improving outcomes in people with acute bacterial meningitis?http://cochraneclinicalanswers.com/doi/10.1002/cca.75/full显示答案
耐药菌株:
未接受第三代头孢菌素类药物治疗患者在出院前应接受利福平、头孢曲松及环丙沙星的治疗,以根除鼻咽部定殖。
确诊的脑膜炎球菌性菌血症治疗
一旦脑膜炎球菌血症不伴脑膜炎确诊(通常在住院后 12 至 48 小时内),患者的抗微生物药物治疗应改为第三代头孢菌素静脉给药或另一种确定性治疗。大多数脑膜炎球菌分离株对苄基青霉素敏感,这可以用于完全敏感的菌株。替代药物包括氨苄西林、美罗培南、氯霉素,或在成人中,使用氟喹诺酮类药物。药物选择取决于患者的个体情况、抗微生物药物敏感性及当地药物可获得情况。
未接受第三代头孢菌素类药物治疗患者在出院前应接受利福平、头孢曲松及环丙沙星的治疗,以根除鼻咽部定殖。