Lymphopenia is associated with late onset Pneumocystis jirovecii pneumonia in solid organ transplantation

Abstract

Background: Pneumocystis jirovecii pneumonia (PJP) affected 5%-15% of solid organ transplant (SOT) recipients prior to universal prophylaxis, classically with trimethoprim-sulfamethoxazole (TMP-SMX). Guidelines generally recommend 6-12 months of prophylaxis post-SOT, yet optimal duration and robust PJP risk stratification have not been established.

Methods: A retrospective, single-center, case-control study of PJP among SOT recipients from January 1998 to December 2013 was conducted. Cases had positive PJ direct fluorescent antibody assay of respiratory specimens. Controls were matched 4:1 by nearest date of SOT. Univariate testing and multivariate logistic regressions were performed.

Results: Fifteen cases were identified among 5505 SOT recipients (0.27% rate) and analyzed vs 60 controls. PJP occurred on average 6.1 years (range 0.9-13.8) post-SOT; no case was receiving PJP prophylaxis at diagnosis. Most were treated with reduced immunosuppression and TMP-SMX plus steroids (80%). Six patients (40%) required critical care; 3 (20%) died. There were no significant demographic differences, though cases tended to be older at SOT (54 vs 48 years, P = .1). In univariate analysis, prior viral infection was more common among cases (67% vs 37%, P = .08). Lower absolute lymphocyte count (ALC) at diagnosis date was strongly associated with PJP (400 vs 1230 × 10⁶ cells/μL, P < .001); odds of infection were high with ALC ≤ 500 × 10⁶ cells (OR 18.7, P < .01).

Conclusion: Pneumocystis jirovecii pneumonia is a rare, late complication of SOT with significant morbidity and mortality. Severe lymphopenia may be useful in identifying SOT recipients who warrant continued or reinstated PJP prophylaxis.

Keywords: Pneumocystis; organ transplantation; pneumonia; prophylaxis.

FIGURE 1

The total number of SOTs performed at our center increased steadily from 1998 to 2006, before plateauing. Indefinite PJP prophylaxis was standard during this period, and among 2598 SOTs performed over 9 y, only 1 PJP case was detected. Due to institutional experience and low incidence of disease, standard protocol changed in mid-2006 (dashed line) to 1 y of PJP prophylaxis post-SOT. A total of 2907 additional patients received a SOT from 2006 to 2013, during which an escalating number of PJP cases (14) were detected, 6 of which were among patients transplanted following the protocol change