静脉内注射免疫球蛋白 (IVIG)
IVIG 可中和许多超抗原,并促进针对链球菌的调理作用。[89]Norrby-Teglund A, Stevens DL. Novel therapies in streptococcal toxic shock syndrome: attenuation of virulence factor expression and modulation of the host response. Curr Opin Infect Dis. 1998;11:285-291.http://www.ncbi.nlm.nih.gov/pubmed/17033393?tool=bestpractice.com一些病例报道使用 IVIG 作为侵袭性 A 族链球菌感染的辅助疗法。[90]Chiu Ch, Ou JT, Chang KS, et al. Successful treatment of severe streptococcal toxic shock syndrome with a combination of intravenous immunoglobulin, dexamethasone and antibiotics. Infection. 1997;25:47-48.http://www.ncbi.nlm.nih.gov/pubmed/9039540?tool=bestpractice.com[91]Perez CM, Kubak BM, Cryer HG, et al. Adjunctive treatment of streptococcal toxic shock syndrome using intravenous immunoglobulin: case report and review. Am J Med. 1997;102:111-113.http://www.ncbi.nlm.nih.gov/pubmed/9209207?tool=bestpractice.com[92]Cawley MJ, Briggs M, Haith LR Jr, et al. Intravenous immunoglobulin as adjunctive therapy for streptococcal toxic shock syndrome associated with necrotizing fasciitis: case report and review. Pharmacotherapy. 1999;19:1094-1098.http://www.ncbi.nlm.nih.gov/pubmed/10610017?tool=bestpractice.com一项观察性队列研究指出,与对照组相比其死亡率显著降低。[93]Kaul R, McGeer A, Norrby-Teglund A, et al. Intravenous immunoglobulin therapy for streptococcal toxic shock syndrome: a comparative observational study. Clin Infect Dis. 1999;28:800-807.http://cid.oxfordjournals.org/content/28/4/800.full.pdf+html?sid=a7b62278-61da-452a-aa40-ce409d6964c6http://www.ncbi.nlm.nih.gov/pubmed/10825042?tool=bestpractice.com相比于葡萄球菌 TSS,链球菌 TSS 更容易被 IVIG 抑制。[94]Darenberg J, Soderquist B, Normark BH, et al. Differences in potency of intravenous polyspecific immunoglobulin G against streptococcal and staphylococcal superantigens: implications for therapy of toxic shock syndrome. Clin Infect Dis. 2004;38:836-842.http://cid.oxfordjournals.org/content/38/6/836.longhttp://www.ncbi.nlm.nih.gov/pubmed/14999628?tool=bestpractice.com在 2003 年,一项多中心随机双盲安慰剂对照试验评估了 IVIG 作为辅助疗法的有效性和安全性。这项研究评估了 28 日死亡率,发现安慰剂对照组的病死率比实验组高出 3.6 倍。[95]Darenberg J, Ihendyane N, Sjolin J, et al. Intravenous immunoglobulin G therapy in streptococcal toxic shock syndrome: a European randomized, double-blind, placebo-controlled trial. Clin Infect Dis. 2003;37:333-340.http://cid.oxfordjournals.org/content/37/3/333.longhttp://www.ncbi.nlm.nih.gov/pubmed/12884156?tool=bestpractice.com死亡率:低质量的证据表明,相对于安慰剂,静脉内免疫球蛋白 (IVIG) 能在两天内更有效地降低脓毒症相关评估评分 (SOFA)。由于入组率低,实验提前终止。[95]Darenberg J, Ihendyane N, Sjolin J, et al. Intravenous immunoglobulin G therapy in streptococcal toxic shock syndrome: a European randomized, double-blind, placebo-controlled trial. Clin Infect Dis. 2003;37:333-340.http://cid.oxfordjournals.org/content/37/3/333.longhttp://www.ncbi.nlm.nih.gov/pubmed/12884156?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)。但这些结果并无统计学意义,试验由于入组率过低而提早终止。[95]Darenberg J, Ihendyane N, Sjolin J, et al. Intravenous immunoglobulin G therapy in streptococcal toxic shock syndrome: a European randomized, double-blind, placebo-controlled trial. Clin Infect Dis. 2003;37:333-340.http://cid.oxfordjournals.org/content/37/3/333.longhttp://www.ncbi.nlm.nih.gov/pubmed/12884156?tool=bestpractice.comIVIG 通常单剂,在数小时内完成给药,尤其是对输液疗法和血管加压支持无反应的严重血流动力学不稳定患者。[96]Keller MA, Stiehm ER. Passive immunity in prevention and treatment of infectious diseases. Clin Microbiol Rev. 2000;13:602-614.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC88952/http://www.ncbi.nlm.nih.gov/pubmed/11023960?tool=bestpractice.com在给出明确建议之前,需要进一步的试验来确证 IVIG 治疗是否可降低患者的死亡率和脓毒症相关评分 (SOFA)。在葡萄球菌 TSS 中并无使用 IVIG 的对照试验。IVIG 可能对链球菌疾病的疗效更佳,但一些研究者提倡在对积极液体支持和血管加压支持无反应的严重链球菌病例使用较高剂量的 IVIG。[94]Darenberg J, Soderquist B, Normark BH, et al. Differences in potency of intravenous polyspecific immunoglobulin G against streptococcal and staphylococcal superantigens: implications for therapy of toxic shock syndrome. Clin Infect Dis. 2004;38:836-842.http://cid.oxfordjournals.org/content/38/6/836.longhttp://www.ncbi.nlm.nih.gov/pubmed/14999628?tool=bestpractice.com[96]Keller MA, Stiehm ER. Passive immunity in prevention and treatment of infectious diseases. Clin Microbiol Rev. 2000;13:602-614.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC88952/http://www.ncbi.nlm.nih.gov/pubmed/11023960?tool=bestpractice.com
高压氧
虽无对照研究,但有报道提到一些 A 族链球菌感染患者接受高压氧治疗。尚不清楚这种疗法是否有益。[97]Bisno AL, Stevens DL. Streptococcal infections of skin and soft tissues. N Engl J Med. 1996;334:240-245.http://www.ncbi.nlm.nih.gov/pubmed/8532002?tool=bestpractice.com[98]Tibbles PM, Edelsberg JS. Hyperbaric-oxygen therapy. N Engl J Med. 1996;334:1642-1648.http://www.ncbi.nlm.nih.gov/pubmed/8628361?tool=bestpractice.com
抗肿瘤坏死因子 (TNF) 抗体
一项在狒狒模型的研究,使用抗肿瘤坏死因子抗体治疗链球菌 TSS,结果令人振奋。[23]Stevens DL. The toxic shock syndromes. Infect Dis Clin North Am. 1996;10:727-746.http://www.ncbi.nlm.nih.gov/pubmed/8958166?tool=bestpractice.com但临床试验尚未进行。在临床实践中抗肿瘤坏死因子抗体并不常规使用,原因是一些对照试验表明它们可能会增加严重感染的风险。[99]Bongartz T, Sutton AJ, Sweeting MJ, et al. Anti-TNF antibody therapy in rheumatoid arthritis and the risk of serious infections and malignancies: systematic review and meta-analysis of rare harmful effects in randomized controlled trials. JAMA. 2006;295:2275-2285.http://jama.ama-assn.org/cgi/content/full/295/19/2275http://www.ncbi.nlm.nih.gov/pubmed/16705109?tool=bestpractice.com
皮质类固醇
在葡萄球菌疾病中使用皮质类固醇的数据有限,但一些研究者证明,皮质类固醇可降低疾病的严重程度。由于死亡率似乎不受影响,未常规推荐在 TSS 中使用皮质类固醇疗法。若出现或疑似肾上腺皮质功能不全,可应用皮质类固醇。
己酮可可碱
己酮可可碱抑制了 TNF-α、白介素-6 和 白介素-11 的生成。(己酮可可碱)在葡萄球菌 TSS 小鼠模型中的已有研究,发现可降低死亡率。人体临床试验尚未进行。