Unanticipated Global Emergence of Multiple Pneumocystis jirovecii Mutants Selected by Mycophenolic Acid Driving Increasing Outbreaks in Solid Organ Transplant Recipients

Association between mycophenolic acid treatment and infection with specific strains of Pneumocystis jirovecii in solid organ transplant recipients in France and Switzerland: a multicentre, retrospective, cross-sectional study.

Inpatient COVID-19 outcomes in solid organ transplant recipients compared to non-solid organ transplant patients: A retrospective cohort.

Mycophenolic acid (MPA) targets the inosine 5′-monophosphate dehydrogenase (IMPDH) of human lymphocytes. It is widely used as an immunosuppressant to prevent rejection in solid organ transplant (SOT) recipients who, incidentally, are at risk for Pneumocystis pneumonia (PCP). We hypothesized that MPA exerts selective pressure on P. jirovecii microorganisms considering its in vitro antifungal activity on other fungi. Thus, we analysed impdh gene in P. jirovecii isolates from SOT recipients. P. jirovecii specimens from 26 patients diagnosed with PCP from 2010 to 2020 were retrospectively examined: 10 SOT recipients treated with MPA and 16 non-SOT patients without prior exposure to MPA. The P. jirovecii impdh gene was amplified and sequenced. Nucleotide sequences were aligned with the reference sequences retrieved from available P. jirovecii whole genomes. The deduced IMPDH protein sequences were aligned with available IMPDH proteins from Pneumocystis spp. and other fungal species known to be in vitro sensitive or resistant to MPA. A total of nine SNPs was identified. One SNP (G1020A) that results in an Ala261Thr substitution was identified in all SOT recipients and in none of the non-SOT patients. Considering that IMPDHs of other fungi, resistant to MPA, harbour Thr (or Ser) at the analogous position, the Ala261Thr mutation observed in MPA-treated patients was considered to represent the signature of P. jirovecii exposure to MPA. These results suggest that MPA may be involved in the selection of specific P. jirovecii strains that circulate in the SOT recipient population.

Serum IFN-γ and RNAemia temporal profiles as biomarkers of severe COVID-19 in solid organ transplant and immunocompetent patients

Outcomes of critically ill solid organ transplant patients with COVID-19 in the United States.

Prevention and treatment of epstein–barr virus‐associated lymphoproliferative disorders in recipients of bone marrow and solid organ transplants

Travel Medicine and Transplant Tourism in Solid Organ Transplantation

A multicenter study to define the epidemiology and outcomes of Clostridioides difficile infection in pediatric hematopoietic cell and solid organ transplant recipients.

Clinical outcomes and serologic response in solid organ transplant recipients with COVID-19: A case series from the United States.

Response to "Is the outcome of SARS-CoV-2 infection in solid organ transplant recipients really similar to that of the general population?"

Prevalence and predictors of SARS-CoV-2 antibodies among solid organ transplant recipients with confirmed infection.

An early experience on the effect of solid organ transplant status on hospitalized COVID-19 patients.

Mortality in solid organ transplant recipients with COVID-19: More than meets the eye

Duodenal Villous Atrophy: A Cause of Chronic Diarrhea After Solid-Organ Transplantation

Pharmacokinetics of Oral Mycophenolate Mofetil in Dog: Bioavailability Studies and the Impact of Antibiotic Therapy