m-TOR inhibitors and risk of Pneumocystis pneumonia after solid organ transplantation: a systematic review and meta-analysis

Eur J Clin Pharmacol. 2019 Nov;75(11):1471-1480. doi: 10.1007/s00228-019-02730-0. Epub 2019 Aug 3.

Abstract

Purpose: Although there is controversy, some evidences proposed increased risk of post-transplant Pneumocystis carinii pneumonia (PCP) in patients receiving mammalian target of rapamycin (mTOR) inhibitors. This study aimed to examine the association between m-TOR inhibitors and the risk of developing PCP in solid organ transplant (SOT) recipients.

Methods: A comprehensive search was performed to find the eligible studies that investigated the incidence of PCP in patients treated with mTOR inhibitors after SOT. Random effect model was applied for meta-analysis.

Results: Combination of 15 effect sizes showed a significant positive association between mTOR inhibitor administration and the risk of PCP (OR = 1.90, 95%CIs = 1.44, 2.75). There was no heterogeneity between studies (I2 = 3.5%). Subgroup analysis revealed increased risk of PCP after the first year of transplantation (P < 0.001).

Conclusion: In conclusion, administration of mTOR inhibitors is a potential risk factor for late-onset PCP after SOT. Targeted PCP prophylaxis based on recipients' risk factors rather universal prophylaxis may lessen the risk.

Keywords: Everolimus; Meta-analysis; Pneumocystis pneumonia; Sirolimus; Solid organ transplant; mTOR inhibitors.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Humans
  • Organ Transplantation*
  • Pneumocystis carinii*
  • Pneumonia, Pneumocystis / epidemiology*
  • Risk Factors
  • TOR Serine-Threonine Kinases / antagonists & inhibitors*

Substances

  • MTOR protein, human
  • TOR Serine-Threonine Kinases