A Multicenter Case-control Study of the Effect of Acute Rejection and Cytomegalovirus Infection on Pneumocystis Pneumonia in Solid Organ Transplant Recipients

Abstract

Pneumocystis pneumonia (PCP) is associated with morbidity and mortality in solid organ transplant (SOT) recipients. In this case-control study, we determined the association between post-transplant PCP and 3 variables: cytomegalovirus infection, allograft rejection and prophylaxis. Eight transplantation centers participated. For each case (SOT recipient with PCP), 3–5 controls (SOT recipients without PCP) were included. Controls were matched to the cases based on transplant center, type of allograft and date of transplantation (± 6 months). We enrolled 53 cases and 209 controls. Transplant types included kidney (n=198), heart (n=30), liver (n=15), kidney-pancreas (n=14) and lung (n=5). PCP occurred beyond 12 months after transplantation in 43 (81.1%) cases. Thirty-four cases (64.1%) required admission to ICU and 28 (52.8%) had mechanical ventilation. Allograft failure occurred in 20 (37.7%) cases and 14 (26.9%) died. No patient developed PCP prophylaxis breakthrough. The proportion of female sex (p= 0.009), kidney dysfunction (p=0.001), cardiac diseases (p=0.005), diabetes mellitus (p=0.03), allograft rejection (p=0.001), CMV infection (p=0.001) and severe lymphopenia (p=0.001) were significantly higher in cases. In logistic regression model, CMV infection (adjusted OR: 4.6, 95% CI: 2.0–10.5) and allograft rejection (adjusted OR: 3.0, 95% CI: 1.5- 6.1) significantly increased the likelihood of PCP. PCP was mostly a late-onset disease occurring after complete course of prophylaxis particularly among patients with CMV infection or allograft rejection. PCP is associated with significant allograft loss. Extended prophylaxis targeting recipients with allograft rejection or CMV infection may reduce the risk of PCP.