Genetic and Epidemiologic Analyses of an Outbreak of Pneumocystis jirovecii Pneumonia Among Kidney Transplant Recipients in the United States

Abstract

Background Pneumocystis jiroveciii is an opportunistic fungus that causes Pneumocystis pneumonia (PCP) in immunocompromised hosts. Over an 11-month period, we observed a rise in cases of PCP among kidney-transplant recipients (KTR), prompting an outbreak investigation. Methods Clinical and epidemiologic data were collected for KTR diagnosed with PCP between July 2019 and May 2020. Pneumocystis strain typing was performed using restriction fragment length polymorphism analyses and multilocus sequence typing in combination with next-generation sequencing. A transmission map was drawn, and a case-control analysis was performed to determine risk factors associated with PCP. Results Nineteen cases of PCP in KTR were diagnosed at a median of 79 months post-transplantation; eight received monthly belatacept infusions. Baseline characteristics were similar for KTR on belatacept versus other regimens; the number of clinic visits was numerically higher for the belatacept group during the study period (median 7.5 vs 3). Molecular typing of respiratory specimens from nine patients revealed coinfection with up to seven P. jirovecii strains per patient. A transmission map suggested multiple clusters of interhuman transmission. In a case-control univariate analysis, belatacept, lower absolute lymphocyte count, non-White race, and more transplant clinic visits were associated with an increased risk of PCP. In multivariate and prediction power estimate analyses, frequent clinic visits was the strongest risk factor for PCP. Conclusion Increased clinic exposure appeared to facilitate multiple clusters of nosocomial PCP transmission among KTR. Belatacept was a risk factor for PCP, possibly by increasing clinic exposure through the need for frequent visits for monthly infusions.

Overall Infectious Complications Related to Belatacept Conversion in Comparison to Tacrolimus in Kidney Transplant Recipients

“…It is noteworthy to disclose a cluster of PJP infections have occurred within our transplant center, which adds to the available evidence of inter-human PJP transmission that may occur within transplant centers. [8][9][10] It is important to consider the inherent risk of infection transmission, such as PJP, with repeated exposure to healthcare facilities that are required for BELA infusions.…”

Risk factors for Pneumocystis jirovecii pneumonia after kidney transplantation: A systematic review and meta‐analysis

“…The additional 73 studies were evaluated furtherly through a full‐text review. Ultimately, a total of 27 retrospective studies published between 1995 and 2022 were included in the meta‐analysis 6,8,14–38 . Among them, 15 studies are from Europe, 6 are from Asia, 5 are from the Americas, and 1 is from Oceania.…”

“…Ultimately, it was found that eight factors are associated with PJP occurrence: age at transplantation, ABO‐incompatibility, acute rejection, CMV infection, BK viremia, anti‐PJP prophylaxis, eGFR and lymphocyte count. Some studies have investigated risk factors for PJP before, such as age, CMV infection, transplant rejection episodes, dialysis time and Tacrolimus dose 7,9,14–38 . However, these conclusions differ, which could be attributed to the fact that people are from different regions of the world.…”

Axenic Long-Term Cultivation of Pneumocystis jirovecii

“…However, single-strand cultures were not the goal of this study—our aim was simply to establish a stable culture at all. A single patient often harbors more than one strain of P. jirovecii at the same time [ 6 , 66 , 67 , 68 ], so the idea of a “single-strain” culture is specious anyway. Therefore, we used mixed P. jirovecii strains from 3 to 4 BALF samples, which stabilized the system and ensured growth in this first attempt, which resulted in 41 successful flask cultures.…”