Burden and Timeline of Infectious Diseases in the First Year After Solid Organ Transplantation in the Swiss Transplant Cohort Study

Abstract

Background: The burden and timeline of posttransplant infections are not comprehensively documented in the current era of immunosuppression and prophylaxis.

Methods: In this prospective study nested within the Swiss Transplant Cohort Study (STCS), all clinically relevant infections were identified by transplant-infectious diseases physicians in persons receiving solid organ transplant (SOT) between May 2008 and December 2014 with ≥12 months of follow-up.

Results: Among 3541 SOT recipients, 2761 (1612 kidney, 577 liver, 286 lung, 213 heart, and 73 kidney-pancreas) had ≥12 months of follow-up; 1520 patients (55%) suffered 3520 infections during the first year posttransplantation. Burden and timelines of clinically relevant infections differed between transplantations. Bacteria were responsible for 2202 infections (63%) prevailing throughout the year, with a predominance of Enterobacteriaceae (54%) as urinary pathogens in heart, lung, and kidney transplant recipients, and as digestive tract pathogens in liver transplant recipients. Enterococcus spp (20%) occurred as urinary tract pathogens in kidney transplant recipients and as digestive tract pathogens in liver transplant recipients, and Pseudomonas aeruginosa (9%) in lung transplant recipients. Among 1039 viral infections, herpesviruses predominated (51%) in kidney, liver, and heart transplant recipients. Among 263 fungal infections, Candida spp (60%) prevailed as digestive tract pathogens in liver transplant recipients. Opportunistic pathogens, including Aspergillus fumigatus (1.4%) and cytomegalovirus (6%), were rare, scattering over 12 months across all SOT recipients.

Conclusions: In the current era of immunosuppression and prophylaxis, SOT recipients experience a high burden of infections throughout the first year posttransplantation, with rare opportunistic pathogens and a predominance of bacteria.

Keywords: bacterial; fungal; infection; solid organ transplant; viral.

Figure 1.

Incidence and distribution of clinically relevant infections by allograft type in 2761 solid organ transplant (SOT) recipients. A, Cumulative incidence censored for competing events (proven infection, graft loss, death, second transplantation) of first clinically relevant infections by allograft type until week 7 after SOT. B, Relative percentage of clinically relevant infections with predominant pathogens by allograft type.

Figure 2.

Distribution by infection site and timeline of infections. A, Distribution (%) of 2202 clinically relevant bacterial, 263 fungal, and 1039 viral infections by infection site and allograft type. Percentages are normalized for each allograft type and represent the relative involvement of each site. B, Temporal distribution of clinically relevant infections by pathogen. Each bar represents an individual event: bacterial (red), viral (blue), and fungal (green) infection. The number of patients under observation is indicated at specific time points. Other gram-positive bacteria: coagulase-negative staphylococci, Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus spp. Enterobacteriaceae: Escherichia coli, Klebsiella spp, Enterobacter spp. Nonfermenting gram-negative bacteria: Pseudomonas aeruginosa, Burkholderia spp, Acinetobacter spp, Stenotrophomonas maltophilia. Opportunistic bacteria: Nocardia spp, Legionella spp, Mycobacteria spp other than tuberculosis. Herpesviruses include herpes simplex virus, varicella zoster virus, and human herpesviruses 6 and 8. Abbreviations: BKPyV, BK polyomavirus; CMV, cytomegalovirus; EBV, Epstein-Barr virus.

Figure 3.

Timelines of the most significant clinically relevant infections for heart (A) and lung (B) transplant recipients according to predominant infection sites. The timeline and relative burden are based on the temporal distribution of 278 infections in 213 heart transplant recipients and 463 infections in 286 lung transplant recipients. Abbreviations: CMV, cytomegalovirus; HSV, herpes simplex virus; VZV, varicella zoster virus.

Figure 4.

Timelines of the most significant clinically relevant infections for kidney (A) and liver (B) transplant recipients according to predominant infection sites. The timeline and relative burden are based on the temporal distribution of 1964 infections in 1612 kidney and 725 infections in 577 liver transplant recipients. Abbreviations: BKPyV, BK polyomavirus; CMV, cytomegalovirus; HCV, hepatitis C virus; HSV, herpes simplex virus; VZV, varicella zoster virus.