治疗主要目标为减轻患者不适,提高生活质量,改善进食。在免疫低下人群保证充分营养及水分摄入相当重要。
此外,对于严重免疫功能低下或虚弱的患者,如果不及时治疗,可能造成口咽念珠菌病局部侵袭或播散。因此,感染的早期诊断,治疗和随访是十分重要的。
对于义齿相关疾病,推荐对义齿进行彻底消毒以达到痊愈目的。[67]Meiller TF, Kelley JI, Jabra-Rizk MA, et al. In vitro studies of the efficacy of antimicrobials against fungi. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2001;91:663-670.http://www.ncbi.nlm.nih.gov/pubmed/11402279?tool=bestpractice.com然而,用泡腾片或含酶溶液浸泡义齿的证据支持尚不足。与其他懈怠的治疗手段相比,用牙膏手动刷洗义齿对于去除菌斑和杀菌更有效。[68]de Souza RF, de Freitas Oliveira Paranhos H, Lovato da Silva CH, et al. Interventions for cleaning dentures in adults. Cochrane Database of Syst Rev. 2009;(4):CD007395.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD007395.pub2/fullhttp://www.ncbi.nlm.nih.gov/pubmed/19821412?tool=bestpractice.com
已发表的指南强调利用浸泡及非磨损性义齿清洁剂手动刷洗来去除义齿菌膜是控制义齿性口炎的有效方法。同时还建议不要持续佩戴假牙(如,每天24小时),这也可以减少义齿性口炎的风险。[69]Felton D, Cooper L, Duqum I, et al. Evidence-based guidelines for the care and maintenance of complete dentures: a publication of the American College of Prosthodontists. J Am Dent Assoc. 2011;142(suppl 1):1-20.http://jada.ada.org/article/S0002-8177(14)63742-9/pdfhttp://www.ncbi.nlm.nih.gov/pubmed/21282672?tool=bestpractice.com[70]Brondani, MA, Samim, F, Feng, H. A conventional microwave oven for denture cleaning: a critical review. Gerodontology. 2012;29:e6-e15.http://onlinelibrary.wiley.com/doi/10.1111/j.1741-2358.2010.00442.x/fullhttp://www.ncbi.nlm.nih.gov/pubmed/21083741?tool=bestpractice.com
白念珠菌对大多数抗菌药物敏感。[65]Pappas PG, Kauffman CA, Andes DR, et al. Clinical practice guideline for the management of candidiasis: 2016 update by the Infectious Diseases Society of America. Clin Infect Dis. 2016;62:e1-e50.https://cid.oxfordjournals.org/content/62/4/e1.full?sid=4827073b-85a7-41bc-bbcb-c5cc007fc23dhttp://www.ncbi.nlm.nih.gov/pubmed/26679628?tool=bestpractice.com大多数患者对局部治疗应答良好。轻度至中度口腔念珠菌病病例可使用唑类抗真菌药(例如,克霉唑、咪康唑)、局部外用多烯类(即制霉菌素)和龙胆紫治疗。[24]Centers for Disease Control and Prevention; National Institutes of Health; HIV Medicine Association of the Infectious Diseases Society of America. Guidelines for prevention and treatment of opportunistic infections in HIV-infected adults and adolescents. April 2015. https://aidsinfo.nih.gov/ (last accessed 26 March 2017).https://aidsinfo.nih.gov/contentfiles/lvguidelines/Adult_OI.pdf[58]Patton LL, Bonito AJ, Shugars DA. A systematic review of the effectiveness of antifungal drugs for the prevention and treatment of oropharyngeal candidiasis in HIV-positive patients. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2001;92:170-179.http://www.ncbi.nlm.nih.gov/pubmed/11505264?tool=bestpractice.com[61]Pienaar ED, Young T, Holmes H. Interventions for the prevention and management of oropharyngeal candidiasis associated with HIV infection in adults and children. Cochrane Database of Syst Rev. 2010;(11):CD003940.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD003940.pub3/fullhttp://www.ncbi.nlm.nih.gov/pubmed/21069679?tool=bestpractice.com[65]Pappas PG, Kauffman CA, Andes DR, et al. Clinical practice guideline for the management of candidiasis: 2016 update by the Infectious Diseases Society of America. Clin Infect Dis. 2016;62:e1-e50.https://cid.oxfordjournals.org/content/62/4/e1.full?sid=4827073b-85a7-41bc-bbcb-c5cc007fc23dhttp://www.ncbi.nlm.nih.gov/pubmed/26679628?tool=bestpractice.com[71]Patton LL, Glick M, eds. Clinician's guide to treatment of HIV-infected patients, 3rd ed. Baltimore: American Academy of Oral Medicine; 2001:11-20.[72]Vazquez JP, Conway J. Randomized, comparative, double-blind, double-dummy, multicenter trial of miconazole buccal tablet and clotrimazole troches for the treatment of oropharyngeal candidiasis: Study of miconazole lauriad efficacy and safety (SMiLES). HIV Clinical Trials. 2010;11:186-196.http://www.ncbi.nlm.nih.gov/pubmed/20974574?tool=bestpractice.com需要注意的是,制霉菌素混悬液蔗糖含量较高,频繁使用,特别是在唾液过少/口腔干燥患者中频繁使用可能会增加龋齿的风险。[7]Reznik DA. Oral manifestations of HIV disease. Top HIV Med. 2005;13:143-148.https://www.iasusa.org/sites/default/files/tam/13-5-143.pdfhttp://www.ncbi.nlm.nih.gov/pubmed/16377852?tool=bestpractice.com
对于重度疾病患者,特别是应用局部药物可能快速复发的 HIV 感染患者,推荐使用全身性唑类药物(例如,氟康唑片、伊曲康唑口服溶液或泊沙康唑混悬液)。[7]Reznik DA. Oral manifestations of HIV disease. Top HIV Med. 2005;13:143-148.https://www.iasusa.org/sites/default/files/tam/13-5-143.pdfhttp://www.ncbi.nlm.nih.gov/pubmed/16377852?tool=bestpractice.com[24]Centers for Disease Control and Prevention; National Institutes of Health; HIV Medicine Association of the Infectious Diseases Society of America. Guidelines for prevention and treatment of opportunistic infections in HIV-infected adults and adolescents. April 2015. https://aidsinfo.nih.gov/ (last accessed 26 March 2017).https://aidsinfo.nih.gov/contentfiles/lvguidelines/Adult_OI.pdf[65]Pappas PG, Kauffman CA, Andes DR, et al. Clinical practice guideline for the management of candidiasis: 2016 update by the Infectious Diseases Society of America. Clin Infect Dis. 2016;62:e1-e50.https://cid.oxfordjournals.org/content/62/4/e1.full?sid=4827073b-85a7-41bc-bbcb-c5cc007fc23dhttp://www.ncbi.nlm.nih.gov/pubmed/26679628?tool=bestpractice.com[33]Sangeorzan JA, Bradley SF, He X, et al. Epidemiology of oral candidiasis in HIV-infected patients: colonization, infection, treatment, and emergence of fluconazole resistance. Am J Med. 1994;97:339-346.http://www.ncbi.nlm.nih.gov/pubmed/7942935?tool=bestpractice.com[73]Cartledge JD, Midgely J, Gazzard BG. Itraconazole solution: higher serum drug concentrations and better clinical response rates than the capsule formulation in acquired immunodeficiency syndrome patients with candidosis. J Clin Pathol. 1997;50:477-480.http://www.ncbi.nlm.nih.gov/pubmed/9378812?tool=bestpractice.com[58]Patton LL, Bonito AJ, Shugars DA. A systematic review of the effectiveness of antifungal drugs for the prevention and treatment of oropharyngeal candidiasis in HIV-positive patients. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2001;92:170-179.http://www.ncbi.nlm.nih.gov/pubmed/11505264?tool=bestpractice.com[74]Pons V, Greenspan D, Debruin M. Therapy for oropharyngeal candidiasis in HIV-infected patients: a randomized, prospective multicenter study of oral fluconazole versus clotrimazole troches. The Multicenter Study Group. J Acquir Immune Defic Syndr. 1993;6:1317-1318.http://www.ncbi.nlm.nih.gov/pubmed/8254467?tool=bestpractice.com[75]Finlay PM, Richardson MD, Robertson AG. A comparative study of the efficacy of fluconazole and amphotericin B in the treatment of oropharyngeal candidosis in patients undergoing radiotherapy for head and neck tumours. Br J Oral Maxillofac Surg. 1996;34:23-25.http://www.ncbi.nlm.nih.gov/pubmed/8645677?tool=bestpractice.com[76]Queiroz-Telles F, Silva N, Carvalho MM, et al. Evaluation of efficacy and safety of itraconazole oral solution for the treatment of oropharyngeal candidiasis in aids patients. Braz J Infect Dis. 2001;5:60-66.http://www.ncbi.nlm.nih.gov/pubmed/11493410?tool=bestpractice.com[77]Graybill JR, Vazquez J, Darouiche RO, et al. Randomized trial of itraconazole oral solution for oropharyngeal candidiasis in HIV/AIDS patients. Am J Med. 1998;104:33-39.http://www.ncbi.nlm.nih.gov/pubmed/9528717?tool=bestpractice.com[78]Phillips P, De Beule K, Frechette G, et al. A double-blind comparison of itraconazole oral solution and fluconazole capsules for the treatment of oropharyngeal candidiasis in patients with AIDS. Clin Infect Dis. 1998;26:1368-1373.http://www.ncbi.nlm.nih.gov/pubmed/9636865?tool=bestpractice.com证据 AHIV感染患者口腔念珠菌病治疗中氟康唑及克霉唑的应用:高级别证据表明,氟康唑在HIV感染患者的口咽念珠菌病的治疗中可抑制念珠菌再定植及复发,疗效持久。克霉唑每天50毫克使用与氟康唑疗效相当。[33]Sangeorzan JA, Bradley SF, He X, et al. Epidemiology of oral candidiasis in HIV-infected patients: colonization, infection, treatment, and emergence of fluconazole resistance. Am J Med. 1994;97:339-346.http://www.ncbi.nlm.nih.gov/pubmed/7942935?tool=bestpractice.com[58]Patton LL, Bonito AJ, Shugars DA. A systematic review of the effectiveness of antifungal drugs for the prevention and treatment of oropharyngeal candidiasis in HIV-positive patients. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2001;92:170-179.http://www.ncbi.nlm.nih.gov/pubmed/11505264?tool=bestpractice.com[74]Pons V, Greenspan D, Debruin M. Therapy for oropharyngeal candidiasis in HIV-infected patients: a randomized, prospective multicenter study of oral fluconazole versus clotrimazole troches. The Multicenter Study Group. J Acquir Immune Defic Syndr. 1993;6:1317-1318.http://www.ncbi.nlm.nih.gov/pubmed/8254467?tool=bestpractice.com系统评价或者受试者>200名的随机对照临床试验(RCT)。证据 AHIV感染患者口咽念珠菌病治疗氟康唑耐药的口咽念珠菌病患者中伊曲康唑混悬液的应用:高级别证据表明,伊曲康唑混悬液在HIV感染患者口咽念珠菌病的治疗中,与氟康唑片剂疗效相当。[77]Graybill JR, Vazquez J, Darouiche RO, et al. Randomized trial of itraconazole oral solution for oropharyngeal candidiasis in HIV/AIDS patients. Am J Med. 1998;104:33-39.http://www.ncbi.nlm.nih.gov/pubmed/9528717?tool=bestpractice.com[78]Phillips P, De Beule K, Frechette G, et al. A double-blind comparison of itraconazole oral solution and fluconazole capsules for the treatment of oropharyngeal candidiasis in patients with AIDS. Clin Infect Dis. 1998;26:1368-1373.http://www.ncbi.nlm.nih.gov/pubmed/9636865?tool=bestpractice.com系统评价或者受试者>200名的随机对照临床试验(RCT)。美国传染病学会 (Infectious Diseases Society of America) 的现行指南建议对重度疾病患者使用氟康唑,而其他唑类药物仅用于氟康唑耐药病例。[65]Pappas PG, Kauffman CA, Andes DR, et al. Clinical practice guideline for the management of candidiasis: 2016 update by the Infectious Diseases Society of America. Clin Infect Dis. 2016;62:e1-e50.https://cid.oxfordjournals.org/content/62/4/e1.full?sid=4827073b-85a7-41bc-bbcb-c5cc007fc23dhttp://www.ncbi.nlm.nih.gov/pubmed/26679628?tool=bestpractice.com然而,NIH-AIDS Info 的现行指南指出,所有唑类药物均为可接受的治疗选择。[24]Centers for Disease Control and Prevention; National Institutes of Health; HIV Medicine Association of the Infectious Diseases Society of America. Guidelines for prevention and treatment of opportunistic infections in HIV-infected adults and adolescents. April 2015. https://aidsinfo.nih.gov/ (last accessed 26 March 2017).https://aidsinfo.nih.gov/contentfiles/lvguidelines/Adult_OI.pdf伊曲康唑口服溶液和泊沙康唑口服混悬液与氟康唑片一样有效,但泊沙康唑口服混悬液的耐受性更好。[24]Centers for Disease Control and Prevention; National Institutes of Health; HIV Medicine Association of the Infectious Diseases Society of America. Guidelines for prevention and treatment of opportunistic infections in HIV-infected adults and adolescents. April 2015. https://aidsinfo.nih.gov/ (last accessed 26 March 2017).https://aidsinfo.nih.gov/contentfiles/lvguidelines/Adult_OI.pdf由于胃肠道吸收不稳定,酮康唑和伊曲康唑胶囊(但不是伊曲康唑混悬液)比氟康唑疗效差,应作为二线方案。[24]Centers for Disease Control and Prevention; National Institutes of Health; HIV Medicine Association of the Infectious Diseases Society of America. Guidelines for prevention and treatment of opportunistic infections in HIV-infected adults and adolescents. April 2015. https://aidsinfo.nih.gov/ (last accessed 26 March 2017).https://aidsinfo.nih.gov/contentfiles/lvguidelines/Adult_OI.pdf[73]Cartledge JD, Midgely J, Gazzard BG. Itraconazole solution: higher serum drug concentrations and better clinical response rates than the capsule formulation in acquired immunodeficiency syndrome patients with candidosis. J Clin Pathol. 1997;50:477-480.http://www.ncbi.nlm.nih.gov/pubmed/9378812?tool=bestpractice.com[79]De Wit S, Clumeck N. Fluconazole in the treatment of fungal infections associated with AIDS. Infection. 1989;17:121-123.http://www.ncbi.nlm.nih.gov/pubmed/2544531?tool=bestpractice.com[80]Phillips P, Zemcov J, Mahmood W, et al. Itraconazole cyclodextrin solution for fluconazole-refractory oropharyngeal candidiasis in AIDS: correlation of clinical response with in vitro susceptibility. AIDS. 1996;10:1369-1376.http://www.ncbi.nlm.nih.gov/pubmed/8902066?tool=bestpractice.com[81]Eichel M, Just-Nubling G, Helm EB, et al. Itraconazole suspension in the treatment of HIV-infected patients with fluconazole-resistant oropharyngeal candidiasis and esophagitis (German). Mycoses. 1996;39(suppl 1):102-106.http://www.ncbi.nlm.nih.gov/pubmed/8767280?tool=bestpractice.com三分之二的氟康唑难治性口咽念珠菌病患者对泊沙康唑口服混悬液有疗效反应,[24]Centers for Disease Control and Prevention; National Institutes of Health; HIV Medicine Association of the Infectious Diseases Society of America. Guidelines for prevention and treatment of opportunistic infections in HIV-infected adults and adolescents. April 2015. https://aidsinfo.nih.gov/ (last accessed 26 March 2017).https://aidsinfo.nih.gov/contentfiles/lvguidelines/Adult_OI.pdf[65]Pappas PG, Kauffman CA, Andes DR, et al. Clinical practice guideline for the management of candidiasis: 2016 update by the Infectious Diseases Society of America. Clin Infect Dis. 2016;62:e1-e50.https://cid.oxfordjournals.org/content/62/4/e1.full?sid=4827073b-85a7-41bc-bbcb-c5cc007fc23dhttp://www.ncbi.nlm.nih.gov/pubmed/26679628?tool=bestpractice.com[82]Schiller DS, Fung HB. Posaconazole: an extended-spectrum triazole antifungal agent. Clin Ther. 2007;29:1862-1886.http://www.ncbi.nlm.nih.gov/pubmed/18035188?tool=bestpractice.com而伊曲康唑口服溶液被认为是替代治疗选择。[24]Centers for Disease Control and Prevention; National Institutes of Health; HIV Medicine Association of the Infectious Diseases Society of America. Guidelines for prevention and treatment of opportunistic infections in HIV-infected adults and adolescents. April 2015. https://aidsinfo.nih.gov/ (last accessed 26 March 2017).https://aidsinfo.nih.gov/contentfiles/lvguidelines/Adult_OI.pdf[81]Eichel M, Just-Nubling G, Helm EB, et al. Itraconazole suspension in the treatment of HIV-infected patients with fluconazole-resistant oropharyngeal candidiasis and esophagitis (German). Mycoses. 1996;39(suppl 1):102-106.http://www.ncbi.nlm.nih.gov/pubmed/8767280?tool=bestpractice.com[83]Saag MS, Fessel WJ, Kaufman CA, et al. Treatment of fluconazole-refractory oropharyngeal candidiasis with itraconazole oral solution in HIV-positive patients. AIDS Res Hum Retroviruses. 1999;15:1413-1417.http://www.ncbi.nlm.nih.gov/pubmed/10555103?tool=bestpractice.com证据 B氟康唑耐药的口咽念珠菌病患者中伊曲康唑混悬液的应用:中等级别的证据表明,在HIV感染患者出现氟康唑治疗失败的口咽念珠菌病时,伊曲康唑混悬液治疗有效。[81]Eichel M, Just-Nubling G, Helm EB, et al. Itraconazole suspension in the treatment of HIV-infected patients with fluconazole-resistant oropharyngeal candidiasis and esophagitis (German). Mycoses. 1996;39(suppl 1):102-106.http://www.ncbi.nlm.nih.gov/pubmed/8767280?tool=bestpractice.com[83]Saag MS, Fessel WJ, Kaufman CA, et al. Treatment of fluconazole-refractory oropharyngeal candidiasis with itraconazole oral solution in HIV-positive patients. AIDS Res Hum Retroviruses. 1999;15:1413-1417.http://www.ncbi.nlm.nih.gov/pubmed/10555103?tool=bestpractice.com受试者<200名的随机对照临床试验(RCT)、受试者>200名且方法学存在缺陷的随机对照临床试验(RCT)、方法学存在缺陷的系统评价或者高质量的观察性(队列)研究。与使用泊沙康唑相关的最常见的不良反应包括头痛、发热、恶心、呕吐及腹泻。[84]Rachwalski EJ, Wieczorkiewicz JT, Scheetz MH. Posaconazole: an oral triazole with an extended spectrum of activity. Annals of Pharmacotherapy. 2008;42:1429-1438.http://www.ncbi.nlm.nih.gov/pubmed/18713852?tool=bestpractice.com酮康唑会引起重度肝损伤与肾上腺功能不全。在2013年7月,欧洲药品管理局人用医药产品委员会(CHMP)推荐口服酮康唑不应被用于真菌感染的治疗,因为治疗的益处不再大于风险。因此,在一些国家口服酮康唑可能无法使用或受限制。本建议不适用于酮康唑外用制剂。[85]Medicines and Healthcare Products Regulatory Agency. Press release: Oral ketoconazole-containing medicines should no longer be used for fungal infections. July 2013. http://www.mhra.gov.uk/ (last accessed 26 March 2017).http://webarchive.nationalarchives.gov.uk/20141205150130/http://www.mhra.gov.uk/NewsCentre/Pressreleases/CON297530[86]European Medicines Agency. European Medicines Agency recommends suspension of marketing authorisations for oral ketoconazole. July 2013. http://www.ema.europa.eu/ema/ (last accessed 26 March 2017).http://www.ema.europa.eu/ema/index.jsp?curl=pages/news_and_events/news/2013/07/news_detail_001855.jsp&mid=WC0b01ac058004d5c1美国食品和药物管理局(FDA)推荐口服酮康唑只可应用于无其他替代药物或其他药物不耐受,治疗的潜在益处大于风险的危及生命的真菌感染情况。但禁用于肝病患者。如果使用,治疗前和治疗过程中应监测肝和肾上腺功能。[87]US Food and Drug Administration. FDA Drug Safety Communication: FDA warns that prescribing of Nizoral (ketoconazole) oral tablets for unapproved uses including skin and nail infections continues; linked to patient death. May 2016. http://www.fda.gov/ (last accessed 29 March 2017).https://www.fda.gov/Drugs/DrugSafety/ucm500597.htm
患者在口服唑类药物治疗时可能出现胃肠道不适,对于治疗持续时间超过21天的患者推荐进行肝毒性定期监测。[24]Centers for Disease Control and Prevention; National Institutes of Health; HIV Medicine Association of the Infectious Diseases Society of America. Guidelines for prevention and treatment of opportunistic infections in HIV-infected adults and adolescents. April 2015. https://aidsinfo.nih.gov/ (last accessed 26 March 2017).https://aidsinfo.nih.gov/contentfiles/lvguidelines/Adult_OI.pdf
具有唑类药物耐药菌株的患者的其他替代化合物包括阿尼芬净、卡泊芬净、米卡芬净、伏立康唑或两性霉素 B。[24]Centers for Disease Control and Prevention; National Institutes of Health; HIV Medicine Association of the Infectious Diseases Society of America. Guidelines for prevention and treatment of opportunistic infections in HIV-infected adults and adolescents. April 2015. https://aidsinfo.nih.gov/ (last accessed 26 March 2017).https://aidsinfo.nih.gov/contentfiles/lvguidelines/Adult_OI.pdf[65]Pappas PG, Kauffman CA, Andes DR, et al. Clinical practice guideline for the management of candidiasis: 2016 update by the Infectious Diseases Society of America. Clin Infect Dis. 2016;62:e1-e50.https://cid.oxfordjournals.org/content/62/4/e1.full?sid=4827073b-85a7-41bc-bbcb-c5cc007fc23dhttp://www.ncbi.nlm.nih.gov/pubmed/26679628?tool=bestpractice.com[88]Sable CA, Nguyen BY, Chodakewitz JA, et al. Safety and tolerability of caspofungin acetate in the treatment of fungal infections. Transpl Infect Dis. 2002;4:25-30.http://www.ncbi.nlm.nih.gov/pubmed/12123423?tool=bestpractice.com[89]Arathoon EG, Gotuzzo E, Noriega LM, et al. Randomized, double-blind, multicenter study of caspofungin versus amphotericin B for treatment of oropharyngeal and esophageal candidiases. Antimicrob Agents Chemother. 2002;46:451-457.http://aac.asm.org/cgi/content/full/46/2/451http://www.ncbi.nlm.nih.gov/pubmed/11796357?tool=bestpractice.com[90]Villanueva A, Arathoon EG, Gotuzzo E, et al. A randomized double-blind study of caspofungin versus amphotericin for the treatment of candidal esophagitis. Clin Infect Dis. 2001;33:1529-1535.http://cid.oxfordjournals.org/content/33/9/1529.longhttp://www.ncbi.nlm.nih.gov/pubmed/11588698?tool=bestpractice.com[91]Villanueva A, Gotuzzo E, Arathoon EG, et al. A randomized double-blind study of caspofungin versus fluconazole for the treatment of esophageal candidiasis. Am J Med. 2002;113:294-299.http://www.ncbi.nlm.nih.gov/pubmed/12361815?tool=bestpractice.com静脉使用两性霉素 B 通常仅用于具有潜在致命性的进展性真菌感染。卡泊芬净耐药白色念珠菌和非白色念珠菌菌株均有报道。[92]Jokela JA, Kaur P. Caspofungin-resistant oral and esophageal candidiasis in a patient with AIDS. AIDS. 2007;21:118-119.http://www.ncbi.nlm.nih.gov/pubmed/17148982?tool=bestpractice.com[93]Hakki M, Staab JF, Marr KA. Emergence of a Candida krusei isolate with reduced susceptibility to caspofungin during therapy. Antimicrob Agents Chemother. 2006;50:2522-2524.http://aac.asm.org/cgi/content/full/50/7/2522http://www.ncbi.nlm.nih.gov/pubmed/16801435?tool=bestpractice.com当使用伊曲康唑治疗失败时,也可使用两性霉素 B 口服混悬液;然而,在一些国家/地区(包括英国和美国),该药还未上市。[24]Centers for Disease Control and Prevention; National Institutes of Health; HIV Medicine Association of the Infectious Diseases Society of America. Guidelines for prevention and treatment of opportunistic infections in HIV-infected adults and adolescents. April 2015. https://aidsinfo.nih.gov/ (last accessed 26 March 2017).https://aidsinfo.nih.gov/contentfiles/lvguidelines/Adult_OI.pdf[65]Pappas PG, Kauffman CA, Andes DR, et al. Clinical practice guideline for the management of candidiasis: 2016 update by the Infectious Diseases Society of America. Clin Infect Dis. 2016;62:e1-e50.https://cid.oxfordjournals.org/content/62/4/e1.full?sid=4827073b-85a7-41bc-bbcb-c5cc007fc23dhttp://www.ncbi.nlm.nih.gov/pubmed/26679628?tool=bestpractice.com
如果考虑静脉使用抗真菌药物治疗,应将患者转诊至传染病主任医生处进行治疗。
口角炎的治疗药物包括制霉菌素和0.1%曲安奈德的复方软膏或乳霜,1%克霉唑软膏,2%咪康唑软膏,及2%酮康唑乳霜。[71]Patton LL, Glick M, eds. Clinician's guide to treatment of HIV-infected patients, 3rd ed. Baltimore: American Academy of Oral Medicine; 2001:11-20.
抗真菌药物可预防性应用于接受放疗或化疗的肿瘤患者,HIV感染的免疫低下患者,或骨髓、实体器官移植受者,以预防局部和全身性念珠菌感染。另有证据表明,在极早期早产儿及极低体重新生儿,预防性口服或外用非吸收性抗真菌药物可降低侵袭性真菌感染的风险。[62]Austin N, Cleminson J, Darlow BA, et al. Prophylactic oral/topical non-absorbed antifungal agents to prevent invasive fungal infection in very low birth weight infants. Cochrane Database Syst Rev. 2015;(10):CD003478.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD003478.pub5/fullhttp://www.ncbi.nlm.nih.gov/pubmed/26497202?tool=bestpractice.com在癌症患者中预防性抗真菌治疗将使患者获益已获得公认,并有强有力的证据表明,从胃肠道吸收的药物在接受治疗的癌症患者中可预防口腔念珠菌病。[53]Meunier F, Paesmans M, Autier P. Value of antifungal prophylaxis with antifungal drugs against oropharyngeal candidiasis in cancer patients. Eur J Cancer B Oral Oncol. 1994;30B:196-199.http://www.ncbi.nlm.nih.gov/pubmed/7920166?tool=bestpractice.com[54]Clarkson JE, Worthington HV, Eden OB. Interventions for preventing oral candidiasis for patients with cancer receiving treatment. Cochrane Database Syst Rev. 2007;(1):CD003807.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD003807.pub3/fullhttp://www.ncbi.nlm.nih.gov/pubmed/17253497?tool=bestpractice.com[55]Worthington HV, Clarkson JE, Khalid T, et al. Interventions for treating oral candidiasis for patients with cancer receiving treatment. Cochrane Database Syst Rev. 2010;(7):CD001972.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD001972.pub4/fullhttp://www.ncbi.nlm.nih.gov/pubmed/17443513?tool=bestpractice.com[56]Lalla RV, Latortue MC, Hong CH, et al. A systematic review of oral fungal infections in patients receiving cancer therapy. Support Care Cancer. 2010;18:985-992.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2914797/?tool=pubmedhttp://www.ncbi.nlm.nih.gov/pubmed/20449755?tool=bestpractice.com证据 A接受癌症治疗患者的预防性抗真菌治疗:高级别证据表明,对于接受癌症治疗的患者,接受胃肠道吸收或部分吸收抗真菌药物预防性治疗的患者与未接受者相比,发生口咽念珠菌病的可能更小。[53]Meunier F, Paesmans M, Autier P. Value of antifungal prophylaxis with antifungal drugs against oropharyngeal candidiasis in cancer patients. Eur J Cancer B Oral Oncol. 1994;30B:196-199.http://www.ncbi.nlm.nih.gov/pubmed/7920166?tool=bestpractice.com[54]Clarkson JE, Worthington HV, Eden OB. Interventions for preventing oral candidiasis for patients with cancer receiving treatment. Cochrane Database Syst Rev. 2007;(1):CD003807.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD003807.pub3/fullhttp://www.ncbi.nlm.nih.gov/pubmed/17253497?tool=bestpractice.com系统评价或者受试者>200名的随机对照临床试验(RCT)。对于正在接受癌症治疗的患者,其口腔念珠菌病的治疗或预防可选用经胃肠道充分吸收的药物(例如,氟康唑)。[54]Clarkson JE, Worthington HV, Eden OB. Interventions for preventing oral candidiasis for patients with cancer receiving treatment. Cochrane Database Syst Rev. 2007;(1):CD003807.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD003807.pub3/fullhttp://www.ncbi.nlm.nih.gov/pubmed/17253497?tool=bestpractice.com[56]Lalla RV, Latortue MC, Hong CH, et al. A systematic review of oral fungal infections in patients receiving cancer therapy. Support Care Cancer. 2010;18:985-992.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2914797/?tool=pubmedhttp://www.ncbi.nlm.nih.gov/pubmed/20449755?tool=bestpractice.com[55]Worthington HV, Clarkson JE, Khalid T, et al. Interventions for treating oral candidiasis for patients with cancer receiving treatment. Cochrane Database Syst Rev. 2010;(7):CD001972.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD001972.pub4/fullhttp://www.ncbi.nlm.nih.gov/pubmed/17443513?tool=bestpractice.com证据 C癌症患者口腔念珠菌感染的根除:低级别证据表明,从胃肠道吸收的抗真菌药物对于根除癌症患者口腔念珠菌病有效。[55]Worthington HV, Clarkson JE, Khalid T, et al. Interventions for treating oral candidiasis for patients with cancer receiving treatment. Cochrane Database Syst Rev. 2010;(7):CD001972.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD001972.pub4/fullhttp://www.ncbi.nlm.nih.gov/pubmed/17443513?tool=bestpractice.com低质量的观察性(队列)研究或者受试者<200名且方法学存在缺陷的随机对照临床试验(RCT)。
在艾滋病患者,已有报道发现制霉菌素可延迟口腔念珠菌病的发病,而在预防口腔念珠菌病发展方面氟康唑被证明比克霉唑更有效。[57]Powderly WG, Finkelstein D, Feinberg J, et al. A randomized trial comparing fluconazole with clotrimazole troches for the prevention of fungal infections in patients with advanced human immunodeficiency virus infection. NIAID AIDS Clinical Trials Group. N Engl J Med. 1995;332:700-705.http://www.nejm.org/doi/full/10.1056/NEJM199503163321102#t=articlehttp://www.ncbi.nlm.nih.gov/pubmed/7854376?tool=bestpractice.com[58]Patton LL, Bonito AJ, Shugars DA. A systematic review of the effectiveness of antifungal drugs for the prevention and treatment of oropharyngeal candidiasis in HIV-positive patients. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2001;92:170-179.http://www.ncbi.nlm.nih.gov/pubmed/11505264?tool=bestpractice.com[59]Havlir DV, Dube MP, McCutchan JA, et al. Prophylaxis with weekly versus daily fluconazole for fungal infections in patients with AIDS. Clin Infect Dis. 1998;27:1369-1375.http://www.ncbi.nlm.nih.gov/pubmed/9868644?tool=bestpractice.com[60]MacPhail LA, Hilton JF, Dodd CL, et al. Prophylaxis with nystatin pastilles for HIV-associated oral candidiasis. J Acquir Immune Defic Syndr Hum Retrovirol. 1996;12:470-476.http://www.ncbi.nlm.nih.gov/pubmed/8757423?tool=bestpractice.com证据 AHIV患者口腔念珠菌病的预防:高级别证据表明,HIV患者预防性应用氟康唑可有效防止口腔念珠菌病的发生。[57]Powderly WG, Finkelstein D, Feinberg J, et al. A randomized trial comparing fluconazole with clotrimazole troches for the prevention of fungal infections in patients with advanced human immunodeficiency virus infection. NIAID AIDS Clinical Trials Group. N Engl J Med. 1995;332:700-705.http://www.nejm.org/doi/full/10.1056/NEJM199503163321102#t=articlehttp://www.ncbi.nlm.nih.gov/pubmed/7854376?tool=bestpractice.com[58]Patton LL, Bonito AJ, Shugars DA. A systematic review of the effectiveness of antifungal drugs for the prevention and treatment of oropharyngeal candidiasis in HIV-positive patients. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2001;92:170-179.http://www.ncbi.nlm.nih.gov/pubmed/11505264?tool=bestpractice.com[59]Havlir DV, Dube MP, McCutchan JA, et al. Prophylaxis with weekly versus daily fluconazole for fungal infections in patients with AIDS. Clin Infect Dis. 1998;27:1369-1375.http://www.ncbi.nlm.nih.gov/pubmed/9868644?tool=bestpractice.com系统评价或者受试者>200名的随机对照临床试验(RCT)。因及时治疗往往有效,多数HIV专科医师不推荐对复发性口咽念珠菌病进行二级预防。[24]Centers for Disease Control and Prevention; National Institutes of Health; HIV Medicine Association of the Infectious Diseases Society of America. Guidelines for prevention and treatment of opportunistic infections in HIV-infected adults and adolescents. April 2015. https://aidsinfo.nih.gov/ (last accessed 26 March 2017).https://aidsinfo.nih.gov/contentfiles/lvguidelines/Adult_OI.pdf但是对于频繁或严重的复发,建议采用口服氟康唑进行预防治疗。[24]Centers for Disease Control and Prevention; National Institutes of Health; HIV Medicine Association of the Infectious Diseases Society of America. Guidelines for prevention and treatment of opportunistic infections in HIV-infected adults and adolescents. April 2015. https://aidsinfo.nih.gov/ (last accessed 26 March 2017).https://aidsinfo.nih.gov/contentfiles/lvguidelines/Adult_OI.pdf[65]Pappas PG, Kauffman CA, Andes DR, et al. Clinical practice guideline for the management of candidiasis: 2016 update by the Infectious Diseases Society of America. Clin Infect Dis. 2016;62:e1-e50.https://cid.oxfordjournals.org/content/62/4/e1.full?sid=4827073b-85a7-41bc-bbcb-c5cc007fc23dhttp://www.ncbi.nlm.nih.gov/pubmed/26679628?tool=bestpractice.com没有足够的数据证明可以就免疫功能受损患者的连续性和间歇性治疗以及在糖尿病患者中使用预防性抗真菌药物提出相关建议。[22]Ship JA, Vissink A, Challacombe SJ. Use of prophylactic antifungals in the immunocompromised host. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2007;103:S6.e1-e14.http://www.ncbi.nlm.nih.gov/pubmed/17379157?tool=bestpractice.com
连续性抑制性治疗使得有较高氟康唑最低抑菌浓度的念珠菌菌株增加,但并不增加氟康唑治疗无效的念珠菌感染发生的风险。[58]Patton LL, Bonito AJ, Shugars DA. A systematic review of the effectiveness of antifungal drugs for the prevention and treatment of oropharyngeal candidiasis in HIV-positive patients. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2001;92:170-179.http://www.ncbi.nlm.nih.gov/pubmed/11505264?tool=bestpractice.com当唑类药物全身性使用大于7到10天时,患者可能出现肝毒性反应[23]Patton LL, McKaig R, Stauss R, et al. Changing prevalence of oral manifestations of human immuno-deficiency virus in the era of protease inhibitor therapy. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2000;89:299-304.http://www.ncbi.nlm.nih.gov/pubmed/10710453?tool=bestpractice.com
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