Long-term outcomes and risk factors for early bacterial infection after pediatric liver transplantation: a prospective cohort study

Abstract

Background: Liver transplantation (LT) is the most efficient treatment for pediatric patients with end-stage liver diseases, while bacterial infection is the leading reason for post-transplant mortality. The present study is to explore the outcomes and risk factors of early bacterial infection (within 1 months) after pediatric LT.

Methods: In this prospective cohort study, 1316 pediatric recipients [median (IQR) age: 9.1 (6.3-28.0) months; male: 48.0%; median (IQR) follow-up time: 40.6 (29.1-51.4) months] who received LT from September 2018 to April 2022 were included. Bacterial culture samples such as sputum, abdominal drainage, blood, and so on were collected when recipients were presented with infective symptoms. Kaplan-Meier analysis was applied to estimate the long-term survival rates and logistic regression was used to identify independent risk factors. To explore the role of pretransplant rectal swab culture (RSC) in reducing post-transplant bacterial infection rate, 188 infant LT recipients [median (IQR) age: 6.8 (5.5-8.1) months; male: 50.5%] from May 2022 to September 2023 were included. Log-binomial regression was used to measure the association of pretransplant RSC screening and post-transplant bacterial infection. The 'Expectation Maximization' algorithm was used to impute the missing data.

Results: Bacterial infection was the primary cause for early (38.9%) and overall mortality (35.6%) after pediatric LT. Kaplan-Meier analysis revealed inferior 1-year and 5-year survival rates for recipients with post-transplant bacterial infection (92.6 vs. 97.1%, 91.8 vs. 96.4%, respectively; P <0.001). Among all detected bacteria, Staphylococcus spp. (34.3%) and methicillin-resistant coagulase-negative Staphylococci (43.2%) were the dominant species and multidrug resistant organisms, respectively. Multivariable analysis revealed that infant recipients [adjusted odds ratio (aOR) 1.49; 95% CI: 1.01-2.20], male recipients (aOR, 1.43; 95% CI: 1.08-1.89), high graft-to-recipient weight ratio (aOR, 1.64; 95% CI: 1.17-2.30), positive post-transplant RSC (aOR, 1.45; 95% CI: 1.04-2.02) and nasopharyngeal swab culture (aOR 2.46; 95% CI: 1.72-3.52) were independent risk factors for early bacterial infection. Furthermore, RSC screening and antibiotic prophylaxis before transplantation could result in a relatively lower post-transplant infection rate, albeit without statistical significance (adjusted RR, 0.53; 95% CI: 0.25-1.16).

Conclusion: In this cohort study, post-transplant bacterial infection resulted in an inferior long-term patient survival rate. The five identified independent risk factors for post-transplant bacterial infection could guide the prophylaxis strategy of post-transplant bacterial infection in the future. Additionally, pretransplant RSC might decrease post-transplant bacterial infection rate.

Figure 1

Flowchart of the subject selection and classification. RJPLT, ** Pediatric Liver Transplantation; RSC, rectal swab culture.

Figure 2

Causes of mortality after pediatric liver transplantation and survival analyses of the pediatric LT recipients. (A) Overall causes of mortality after pediatric LT (liver transplantation). (B) Causes of mortality after pediatric LT within the first month. (C-D) Kaplan–Meier analysis of the patient (C) and graft (D) survival rates in pediatric recipients with or without bacterial infection after LT. Notes: Multivariable Cox regression model for investigating the association of post-transplant bacterial infection with the all-cause patient mortality (C) adjusted for indication, LT type, massive blood loss, positive post-transplant RSC (rectal swab culture), length of ICU stay, length of hospital stay, grade III–IV complication and acute rejection. Multivariable Cox regression model for investigating the association of post-transplant bacterial infection with the all-cause graft loss (D) adjusted for total bilirubin > 3 ULN (upper limit of normal value), blood type incompatibility, LT type, graft type, massive blood loss, positive post-transplant RSC, length of ICU stay, length of hospital stay, grade III–IV complication, acute and chronic rejection. PTLD, post-transplant lymphoproliferative disorder; PGD, primary graft dysfunction (including primary nonfunctional and initial poor function); ARDS, acute respiratory distress syndrome; cHR, crude hazard ratio; aHR, adjusted hazard ratio.

Figure 3

Multivariable logistic regression analysis for investigating the risk factors of post-transplant bacterial infection. Notes: Independent risk factors (P-value <0.05) for post-transplant bacterial infection were colored burgundy, and insignificant variables (P-value ≥0.05) are colored deep sky blue. Ref indicated the reference used in the multivariable logistic regression. aOR, adjusted odds ratio; ALB, albumin; ALT, alanine aminotransferase; ULN, upper limit of normal value; TB, total bilirubin; DDLT, deceased donor liver transplantation; LDLT, living donor liver transplantation; GRWR, graft-to-recipient weight ratio; RY, Roux-en-Y; HJ, hepaticojejunostomy; RSC, rectal swab culture; NPSC, nasopharyngeal swab culture.

Figure 4

Incidences and microbial spectrums of post-transplant bacterial and MDRO infection. (A) Bacterial and MDRO (multidrug-resistant organism) infection rates in different sites after pediatric liver transplantation. (B) Microbial composition of bacteria in different infection sites after pediatric liver transplantation. (C) GPB (gram-positive bacteria) and GNB (gram-negative bacteria) infection rates in different sites after pediatric liver transplantation. (D) Microbial composition of MDROs in different infection sites after pediatric liver transplantation. LRTI, lower respiratory tract infection; IAI, intra-abdominal infection; BSI, bloodstream infection; CR-BSI, catheter-related bloodstream infection; RSC, rectal swab culture; NPSC, nasopharyngeal swab culture; E. coli, Escherichia coli; S. maltophilia, Stenotrophomonas maltophilia; CNS, coagulase-negative staphylococci; S. aureus, Staphylococcus aureus; MRSA, methicillin-resistant S. aureus; MR-CNS, methicillin-resistant CNS; CRE, carbapenem-resistant Enterobacteriaceae; VRE, vancomycin-resistant Enterococcus; CR-AB, carbapenem-resistant Acinetobacter baumanii; ESBL, extended-spectrum β-lactamase.