<p class="ql-block">成人肾小球肾炎治疗时<span style="font-size:18px;">预防卡肺（PCP）的建议（PCP Prophylaxis Recommendations.Ontario Health Ontario Renal Network.）</span></p><p class="ql-block">应用免疫抑制剂药物时预防卡肺感染的预防用药时间问题：</p><p class="ql-block">应用免疫抑制治疗膜性肾病和ANCA相关小血管炎肾损害等疾病时，需要应用复方磺胺甲恶唑片预防卡肺感染，但用药时长目前还不规范且尚未引起大家重视，那么利妥昔单抗类风湿性关节炎治疗方案即1.0g/次/2周 x 2次和利妥昔单抗治疗淋巴瘤方案即357mg/kg/次/周 x 4次、CTX及激素时，预防卡肺感染的复方磺胺甲恶唑用药时间应该多久呢？</p><p class="ql-block">见：PCP Prophylaxis Recommendations.Ontario Health Ontario Renal Network（预防卡肺（PCP）的建议）.</p> <p class="ql-block">表1是对接受免疫抑制治疗的GN患者预防卡肺（PCP）预防治疗剂量和预防时间的建议。</p><p class="ql-block">免疫抑制剂环磷酰胺治疗时复方磺胺甲恶唑片预防时间建议【1】：</p><p class="ql-block">1、考虑对所有患者进行预防，并在停用环磷酰胺后至少持续3个月。</p><p class="ql-block"><b>证据：</b></p><p class="ql-block">根据血管炎指南推断【2】。</p><p class="ql-block">风湿性疾病患者病例对照研究【3】。</p><p class="ql-block">ANCA相关性血管炎患者是PCP风险最高人群【2】。</p><p class="ql-block"><b>证据不足：</b></p><p class="ql-block">SLE患者复方磺胺甲恶唑预防没有降低卡肺的风险，建议临床医生不考虑预防【3.4】。</p><p class="ql-block">参考文献：</p><p class="ql-block">1.Stringer, James R.; Beard, Charles B.; Miller, Robert F.; Wakefield, Ann E. (Sep 2002). "A New Name for Pneumocystis from Humans and New Perspectives on the Host-Pathogen Relationship". Emerg Infect Dis. 2002; 8: 891–896 </p><p class="ql-block">2.McGeoch L et al. CanVasc Recommendations for the Management of Antineutrophil Cytoplasm Antibodyassociated Vasculitides. J of Rheum 2015;42:1-24</p><p class="ql-block">3.Park JW, Curtis JR, Moon J et al. Prophylactic effect of trimethoprim-sulfamethoxazole for pneumocystis pneumonia in patients with rheumatic diseases exposed to prolonged high-dose glucocorticoids. Ann Rheum Dis 2017;0:1-6</p><p class="ql-block">4.Gupta D et al. Prophylactic Antibiotic Usage for Pneumocystic jirovecii Pneumonia in Patients with Systemic Lupus Erythematosus on Cyclophosphamide. A Survey of US Rheumatologists and the Review of the Literature. J Clin Rheumatol 2008;14:267-72.</p> <p class="ql-block">应用利妥昔单抗治疗时复方磺胺甲恶唑预防时间建议【5】：</p><p class="ql-block">1、考虑对所有接受利妥昔单抗治疗的患者进行预防，并在接受利妥昔单抗后至少持续6个月或直到B细胞充盈为止。</p><p class="ql-block">2、接受利妥昔单抗维持治疗的患者应继续持续预防。</p><p class="ql-block">证据：</p><p class="ql-block">根据血管炎指南推断【2】。</p><p class="ql-block">基于回顾性横断面研究的预防持续时间【6】。</p><p class="ql-block">参考文献：</p><p class="ql-block">1.Stringer, James R.; Beard, Charles B.; Miller, Robert F.; Wakefield, Ann E. (Sep 2002). "A New Name for </p><p class="ql-block">Pneumocystis from Humans and New Perspectives on the Host-Pathogen Relationship". Emerg Infect Dis. 2002; 8: 891–896 </p><p class="ql-block">2.McGeoch L et al. CanVasc Recommendations for the Management of Antineutrophil Cytoplasm Antibodyassociated Vasculitides. J of Rheum 2015;42:1-24</p><p class="ql-block">3.Park JW, Curtis JR, Moon J et al. Prophylactic effect of trimethoprim-sulfamethoxazole for pneumocystis pneumonia in patients with rheumatic diseases exposed to prolonged high-dose glucocorticoids. Ann Rheum Dis 2017;0:1-6.</p><p class="ql-block">4.Gupta D et al. Prophylactic Antibiotic Usage for Pneumocystic jirovecii Pneumonia in Patients with Systemic Lupus Erythematosus on Cyclophosphamide. A Survey of US Rheumatologists and the Review of the Literature. J Clin Rheumatol 2008;14:267-72.</p><p class="ql-block">5.Wolfe RM, Peacock JE. Pneumocystis Pneumonia and the Rheumatologist: Which patients Are At Risk and How Can PCP Be Prevented? Curr Rheumatol Rep 2017;19(35):4-10.</p><p class="ql-block">6.Martin-Garrido I et al. Pneumocystis Pneumonia in Patients Treated with Rituximab. CHEST 2013;144(1):258-65.</p> <p class="ql-block">应用激素治疗时复方磺胺甲恶唑预防时间建议【3】：</p><p class="ql-block">在以下情况下可以考虑开始预防：</p><p class="ql-block">泼尼松剂量>30mg/天（或同等剂量）计划持续时间>4周【3】。</p><p class="ql-block">当剂量达到<span style="font-size:18px;"><15mg/天</span>以下水平时停止预防【3】。</p><p class="ql-block">证据：</p><p class="ql-block"><span style="font-size:18px;">风湿性疾病</span>患者的病例对照研究【3】。</p><p class="ql-block">参考文献：</p><p class="ql-block">3.Park JW, Curtis JR, Moon J et al. Prophylactic effect of trimethoprim-sulfamethoxazole for pneumocystis pneumonia in patients with rheumatic diseases exposed to prolonged high-dose glucocorticoids. Ann Rheum Dis 2017;0:1-6.</p> <p class="ql-block">应用三联免疫抑制时应用复方磺胺甲恶唑预防卡肺的时间：</p><p class="ql-block">考虑接受以下<span style="font-size:18px;">三联免疫抑制疗法的</span>患者进行预防</p><p class="ql-block">三联免疫抑制疗法即：钙调神经磷酸酶抑制剂（CsY）+霉酚酸酯和甲氨蝶呤/和或硫唑嘌呤+低剂量泼尼松。</p><p class="ql-block"><br></p><p class="ql-block">三重免疫抑制增加了免疫抑制的总体净状态，导致PCP的风险【8】，鉴于缺乏PCP的证据和指南，对于肾小球肾炎患者的预防，推断移植指南可能是合理的，对接受三联疗法的肾小球肾炎患者的建议见实体器官移植指南：建议所有患者在移植后至少6-12个月内进行常规PCP预防，以及建议延长持续时间【1】。</p><p class="ql-block">证据：</p><p class="ql-block">肾脏推断移植指南【6,7】。</p><p class="ql-block">参考文献：</p><p class="ql-block">6.Martin-Garrido I et al. Pneumocystis Pneumonia in Patients Treated with Rituximab. CHEST 2013;144(1):258-</p><p class="ql-block">65.</p><p class="ql-block">7.Kidney Disease: Improving Global Outcomes (KDIGO) Transplant Work Group. KDIGO clinical practice </p><p class="ql-block">guideline for the care of kidney transplant recipients. American Journal of Transplantation 2009; 9(Suppl 3): </p><p class="ql-block">S1–S157.</p><p class="ql-block">8.Martin SI, Fishman JA et al. Pneumocystis Pneumonia in Solid Organ Transplantation. American Journal of
Transplantation 2013;13:272-9.
</p><p class="ql-block">9.The Renal Drug Handbook (Third Edition), Ashley C, Currie A, UK Renal Pharmacy Group. Radcliffe Publishing
Oxford, New York, 2009.
</p><p class="ql-block">10.Sulfamethoxazole/Trimethoprim. In: In Depth Answers [database on the Internet]. Greenwood Village (CO):
Truven Health Analytics; 2017 [cited 2019 April 30]. Available from: www.micromedexsolutions.com.
Subscription required to view.
</p><p class="ql-block">11 Vargas SL, Hughes WT, San</p> <p class="ql-block">预防卡氏肺孢子虫肺炎的一线药物是磺胺甲恶唑（SMX）/甲氧苄啶（TMP），通常使用预防剂量为1片单强度片剂（SMX:400mg/TMP:80mg），每日一次，或1片双强度片剂（SMX:800mg/TMP:160mg）每周三次。</p><p class="ql-block">需要将肾脏剂量调整到常规剂量的一半，对于CrCl 15-30mL/min（即每周三次，每次一片）【8.9】。</p><p class="ql-block">对于CrCl<15mL/min的产品专论建议避免使用，但其他参考文献建议使用常规剂量的一半【9.10】。</p><p class="ql-block">建议密切监测血清肌酐和电解质。</p><p class="ql-block">对于因安全性或耐受性问题而无法使用SMX/TMP的患者，可选择二线治疗。</p><p class="ql-block">预防药物包括氨苯砜100mg每日一次或阿托伐醌1500mg每日一次。</p><p class="ql-block">参考文献：</p><p class="ql-block">8.Martin SI, Fishman JA et al. Pneumocystis Pneumonia in Solid Organ Transplantation. American Journal of Transplantation 2013;13:272-9.</p><p class="ql-block">9.The Renal Drug Handbook (Third Edition), Ashley C, Currie A, UK Renal Pharmacy Group. Radcliffe Publishing Oxford, New York, 2009.</p><p class="ql-block">10.Sulfamethoxazole/Trimethoprim. In: In Depth Answers [database on the Internet]. Greenwood Village (CO): Truven Health Analytics; 2017 [cited 2019 April 30]. Available from: www.micromedexsolutions.com. Subscription required to view.11 Vargas.</p>