A Comprehensive Evaluation of Risk Factors for Pneumocystis jirovecii Pneumonia in Adult Solid Organ Transplant Recipients: A Systematic Review and Meta-analysis

Abstract

Background. There is no consensus guidance on when to reinitiate Pneumocystis jirovecii pneumonia (PJP) prophylaxis in solid organ transplant (SOT) recipients at increased risk. The 2019 American Society of Transplantation Infectious Diseases Community of Practice (AST IDCOP) guidelines suggested to continue or reinstitute PJP prophylaxis in those receiving intensified immunosuppression for graft rejection, cytomegalovirus (CMV) infection, higher dose of corticosteroids, or prolonged neutropenia. Methods. A literature search was conducted evaluating all literature from existence through April 22, 2020, using MEDLINE and EMBASE. (The International Prospective Register of Systematic Reviews registration number: CRD42019134204). Results. A total of 30 studies with 413 276 SOT recipients were included. The following factors were associated with PJP development: acute rejection (pooled odds ratio [pOR], 2.35; 95% confidence interval [CI], 1.69-3.26); study heterogeneity index [I2] = 23.4%), CMV-related illnesses (pOR, 3.14; 95% CI, 2.30-4.29; I2 = 48%), absolute lymphocyte count <500 cells/mm3 (pOR, 6.29; 95% CI, 3.56-11.13; I2 = 0%), BK polyomavirus-related diseases (pOR, 2.59; 95% CI, 1.22-5.49; I2 = 0%), HLA mismatch ≥3 (pOR, 1.83; 95% CI, 1.06-3.17; I2 = 0%), rituximab use (pOR, 3.03; 95% CI, 1.82-5.04; I2 = 0%), and polyclonal antibodies use for rejection (pOR, 3.92; 95% CI, 1.87-8.19; I2 = 0%). On the other hand, sex, CMV mismatch, interleukin-2 inhibitors, corticosteroids for rejection, and plasmapheresis were not associated with developing PJP. Conclusions. PJP prophylaxis should be considered in SOT recipients with lymphopenia, BK polyomavirus-related infections, and rituximab exposure in addition to the previously mentioned risk factors in the American Society of Transplantation Infectious Diseases Community of Practice guidelines.

Does Post-Transplant Cytomegalovirus Increase the Risk of Invasive Aspergillosis in Solid Organ Transplant Recipients? A Systematic Review and Meta-Analysis

“…IA is associated with high rates of graft loss and mortality, with a 12-month survival of 59% [ 13 , 14 ]. CMV infection has been a well-described risk factor for post-transplant Pneumocystis jirovecii pneumonia (PJP), formerly known as Pneumocystis carinii pneumonia (PCP) [ 15 , 16 , 17 ]. However, there are conflicting data with respect to the impact of post-transplant CMV on subsequent IA occurrence in SOT recipients.…”

Detection of Pneumocystis jirovecii in Patients with Severe COVID-19: Diagnostic and Therapeutic Challenges

“…A case was described in a newly diagnosed HIV patient with COVID-19 who presented a severe depletion of CD4 T cells, fine reticular changes in CT scan, and an elevated level of lactate dehydrogenase (LDH), successfully treated with TMP-SMX [3]. Another case involved a renal transplant recipient with lymphocytopenia treated with tacrolimus, mycophenolate mofetil, and methylprednisolone [4,9]. He died despite a treatment by TMP-SMX.…”

Current status of glucocorticoid usage in solid organ transplantation

“…Taking GCs is a risk factor for fungal infections, including mucormycosis[ 71 ] and invasive Aspergyllosis [ 72 , 73 ]. Although the American Society of Transplantation suggests re-initiation of Pneumocystis jirovecii pneumonia (PJP) prophylaxis with intensification of immunosuppression, such as treatment of acute rejection with GCs[ 74 ], the association between GC bolus for acute rejection and PJP remains controversial[ 75 ]. While a French case-control study exhibited GC bolus administration for acute rejection in kidney transplant patients as an independent factor correlated with PJP[ 76 ] and a Korean study showed that taking GCs is significantly associated with PJP[ 77 ], a meta-analysis found that GC injections for acute rejection did not increase the risk of PJP[ 75 ].…”