Butler-Laporte Guillaume, Smyth Elizabeth, Amar-Zifkin Alexandre, Cheng Matthew P, McDonald Emily G, Lee Todd C
Division of Infectious Diseases, Department of Medicine, McGill University Health Centre, Montréal, Québec, Canada.
Research Institute of the McGill University Health Centre, Montréal, Québec, Canada.
Open Forum Infect Dis. 2020 Apr 2;7(5):ofaa112. doi: 10.1093/ofid/ofaa112. eCollection 2020 May.
pneumonia (PJP) remains a common and highly morbid infection for immunocompromised patients. Trimethoprim-sulfamethoxazole (TMP-SMX) is the antimicrobial treatment of choice. However, treatment with TMP-SMX can lead to significant dose-dependent renal and hematologic adverse events. Although TMP-SMX is conventionally dosed at 15-20 mg/kg/d of trimethoprim for the treatment of PJP, reduced doses may be effective and carry an improved safety profile.
We conducted a systematic search in the Medline, Embase, and Cochrane Library databases from inception through March 2019 for peer-reviewed studies reporting on reduced doses of TMP-SMX (15 mg/kg/d of trimethoprim or less) for the treatment of PJP. PRISMA, MOOSE, and Cochrane guidelines were followed. Gray literature was excluded.
Ten studies were identified, and 6 were included in the meta-analysis. When comparing standard doses with reduced doses of TMP-SMX, there was no statistically significant difference in mortality (absolute risk difference, -9% in favor of reduced dose; 95% confidence interval [CI], -27% to 8%). When compared with standard doses, reduced doses of TMP-SMX were associated with an 18% (95% CI, -31% to -5%) absolute risk reduction of grade ≥3 adverse events.
In this systematic review, treatment of PJP with doses of ≤10 mg/kg/d of trimethoprim was associated with similar rates of mortality when compared with standard doses and with significantly fewer treatment-emergent severe adverse events. Although limited by the observational nature of the studies included, this review provides the most current available evidence for the optimal dosing of TMP-SMX in the treatment of PJP.
肺孢子菌肺炎（PJP）对于免疫功能低下的患者而言，仍然是一种常见且致死率很高的感染性疾病。复方磺胺甲恶唑（TMP-SMX）是首选的抗菌治疗药物。然而，使用TMP-SMX进行治疗可能会导致显著的剂量依赖性肾脏和血液学不良事件。虽然传统上TMP-SMX治疗PJP的剂量为甲氧苄啶15 - 20mg/（kg·d），但降低剂量可能同样有效且安全性更高。
我们在Medline、Embase和Cochrane图书馆数据库中进行了系统检索，检索时间从建库至2019年3月，以查找关于降低剂量的TMP-SMX（甲氧苄啶剂量为15mg/（kg·d）或更低）治疗PJP的同行评审研究。遵循PRISMA、MOOSE和Cochrane指南。排除灰色文献。
共识别出10项研究，其中6项纳入荟萃分析。比较TMP-SMX标准剂量与降低剂量时，死亡率无统计学显著差异（绝对风险差，降低剂量组更有利，为-9%；95%置信区间[CI]，-27%至8%）。与标准剂量相比，降低剂量的TMP-SMX可使≥3级不良事件的绝对风险降低18%（95%CI，-31%至-5%）。
在本系统评价中，与标准剂量相比，使用剂量≤10mg/（kg·d）甲氧苄啶治疗PJP的死亡率相似，且治疗中出现的严重不良事件显著减少。尽管本评价受纳入研究的观察性性质限制，但它为TMP-SMX治疗PJP的最佳给药剂量提供了最新的现有证据。
