Department of Pharmacy, The Affiliated Hospital of North Sichuan Medical College, Sichuan, Nanchong, China.
Department of Pharmacy, Nanchong Central Hospital, The Second Affiliated Clinical Medical College of North Sichuan Medical College, Sichuan, Nanchong, China.
PLoS One. 2021 Mar 25;16(3):e0248524. doi: 10.1371/journal.pone.0248524. eCollection 2021.
Pneumocystis pneumonia (PCP) has a significant impact on the mortality of immunocompromised patients. It is not known whether the prophylactic application of trimethoprim-sulfamethoxazole (TMP-SMZ) can reduce the incidence of PCP and mortality in the human immunodeficiency virus (HIV)-negative immunodeficient population. The safety profile is also unknown. There have been few reports on this topic. The aim of this study was to systematically evaluate the efficacy and safety of the use of TMP-SMZ for the prevention of PCP in this population of patients from the perspective of evidence-based medicine.
A comprehensive search without restrictions on publication status or other parameters was conducted. Clinical randomized controlled trials (RCTs) or case-control trials (CCSs) of TMP-SMZ used for the prevention of PCP in HIV-negative immunocompromised populations were considered eligible. A meta-analysis was performed using the Mantel-Haenszel fixed-effects model or Mantel-Haenszel random-effects model, and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated and reported.
Of the 2392 records identified, 19 studies (n = 4135 patients) were included. The efficacy analysis results indicated that the PCP incidence was lower in the TMP-SMZ group than in the control group (OR = 0.27, 95% CI (0.10, 0.77), p = 0.01); however, the rate of drug discontinuation was higher in the TMP-SMZ group than in the control group (OR = 14.31, 95% CI (4.78, 42.91), p<0.00001). In addition, there was no statistically significant difference in the rate of mortality between the two groups (OR = 0.54, 95% CI (0.21, 1.37), p = 0.19). The safety analysis results showed that the rate of adverse events (AEs) was higher in the TMP-SMZ group than in the control group (OR = 1.92, 95% CI (1.06, 3.47), p = 0.03).
TMP-SMZ has a better effect than other drugs or the placebo with regard to preventing PCP in HIV-negative immunocompromised individuals, but it may not necessarily reduce the rate of mortality, the rate of drug discontinuation or AEs. Due to the limitations of the research methodologies used, additional large-scale clinical trials and well-designed research studies are needed to identify more effective therapies for the prevention of PCP.
卡氏肺孢子虫肺炎（PCP）对免疫功能低下患者的死亡率有重大影响。目前尚不清楚复方磺胺甲噁唑（TMP-SMZ）的预防性应用是否可以降低 HIV 阴性免疫缺陷人群中 PCP 的发病率和死亡率。其安全性概况也未知。关于这个话题的报道很少。本研究旨在从循证医学的角度系统评估 TMP-SMZ 用于预防该人群 PCP 的疗效和安全性。
全面检索，不限制出版状态或其他参数。考虑纳入 TMP-SMZ 用于预防 HIV 阴性免疫缺陷人群 PCP 的临床随机对照试验（RCT）或病例对照试验（CCS）。使用 Mantel-Haenszel 固定效应模型或 Mantel-Haenszel 随机效应模型进行荟萃分析，并报告比值比（OR）及其 95%置信区间（CI）。
在 2392 条记录中，有 19 项研究（n = 4135 例患者）入选。疗效分析结果表明，TMP-SMZ 组 PCP 发生率低于对照组（OR = 0.27，95%CI（0.10，0.77），p = 0.01）；但 TMP-SMZ 组停药率高于对照组（OR = 14.31，95%CI（4.78，42.91），p<0.00001）。此外，两组死亡率无统计学差异（OR = 0.54，95%CI（0.21，1.37），p = 0.19）。安全性分析结果显示，TMP-SMZ 组不良事件（AE）发生率高于对照组（OR = 1.92，95%CI（1.06，3.47），p = 0.03）。
TMP-SMZ 在预防 HIV 阴性免疫缺陷个体的 PCP 方面优于其他药物或安慰剂，但不一定能降低死亡率、停药率或 AE 发生率。由于研究方法的局限性，需要开展更多的大规模临床试验和精心设计的研究来确定更有效的 PCP 预防治疗方法。
