Retrospective Cohort Study
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Dec 7, 2020; 26(45): 7191-7203
Published online Dec 7, 2020. doi: 10.3748/wjg.v26.i45.7191
High mortality associated with gram-negative bacterial bloodstream infection in liver transplant recipients undergoing immunosuppression reduction
Fang Chen, Xiao-Yun Pang, Chuan Shen, Long-Zhi Han, Yu-Xiao Deng, Xiao-Song Chen, Jian-Jun Zhang, Qiang Xia, Yong-Bing Qian
Fang Chen, Xiao-Yun Pang, Department of Pharmacy, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200127, China
Chuan Shen, Long-Zhi Han, Xiao-Song Chen, Jian-Jun Zhang, Qiang Xia, Yong-Bing Qian, Department of Liver Surgery, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200127, China
Yu-Xiao Deng, Department of Critical Care Medicine, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200127, China
Author contributions: Chen F and Qian YB designed the study; Pang XY, Shen C, Han LZ, Chen XS, Zhang JJ, and Deng YX participated in the acquisition, analysis, and interpretation of the data; Chen F, Qian YB, and Deng YX drafted the initial manuscript; Zhang JJ, Xia Q, and Qian YB revised the article critically for important intellectual content.
Supported by the National Key R&D Precision Medicine Program, No. 2017YFC0908100; and Shanghai Key Clinical Specialty Grant, No. Shslczdzk05801.
Institutional review board statement: The study was reviewed and approved by Renji Hospital, Shanghai Jiaotong University School of Medicine Review Board (Approval No. KY2019-160).
Informed consent statement: The informed consent was waived by the ethics committee.
Conflict-of-interest statement: All authors declare no conflicts of interest regarding the conduct and publication of this study.
Data sharing statement: No additional data are available.
STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Yong-Bing Qian, MD, Associate Professor, Department of Liver Surgery, Renji Hospital, School of Medicine, Shanghai Jiaotong University, No. 1630 Dongfang Road, Shanghai 200127, China.
Received: September 17, 2020
Peer-review started: September 17, 2020
First decision: October 17, 2020
Revised: October 30, 2020
Accepted: November 9, 2020
Article in press: November 9, 2020
Published online: December 7, 2020
Research background

Bacterial infections continue to be the most common infectious complication after liver transplantation (LT), usually within 2 mo after LT. Immunosuppression (IS) is the single most important factor contributing to the incidence of infections in transplant recipients.

Research motivation

The management of IS therapy during infection after LT is highly controversial, although IS reduction (partially discontinue or reduce the dosage of at least one IS agent) or complete withdrawal may be a generally accepted option in life-threatening infections. Few studies are available on the management of IS treatment in the LT recipients complicated with infection.

Research objectives

To describe our experience in the management of IS treatment during bacterial bloodstream infection (BSI) in LT recipients and assess the effect of temporary IS withdrawal on 30 d mortality of recipients presenting with severe infection.

Research methods

A retrospective study was conducted with the patients diagnosed with BSI after LT in the Department of Liver Surgery, Renji Hospital from January 1, 2016 through December 31, 2017. All recipients diagnosed with BSI infections after LT were included in this study. Univariate and multivariate Cox regression analysis of risk factors for 30 d mortality was conducted in LT patients with Gram-negative bacterial (GNB) infections.

Research results

Seventy-four episodes of BSI were identified in 70 LT recipients, including 45 episodes of Gram-positive bacterial (GPB) infections in 42 patients and 29 episodes of Gram-negative bacterial infections in 28 patients. Overall, IS reduction (at least 50% dose reduction or cessation of one or more immunosuppressive agent) was made in 28 (41.2%) cases, specifically, in 5 (11.9%) cases with GPB infections and 23 (82.1%) cases with GNB infection. The 180 d all-cause mortality rate was 18.5% (13/70). The mortality rate in GNB group (39.3%, 11/28) was significantly higher than that in GPB group (4.8%, 2/42) (P = 0.001). All the deaths in GNB group were attributed to worsening infection secondary to IS withdrawal but the deaths in GPB group were all due to graft-versus-host disease. GNB group was associated with significantly higher incidence of intra-abdominal infection, IS reduction, and complete IS withdrawal than GPB group (P < 0.05). Cox regression showed that rejection (adjusted hazard ratio 7.021, P = 0.001) and complete IS withdrawal (adjusted hazard ratio 12.65, P = 0.019) were independent risk factors for 30 d mortality in patients with GNB infections after LT.

Research conclusions

IS reduction is more frequently associated with GNB infection than GPB infection in LT recipients. Complete IS withdrawal should be cautious due to increased risk of mortality in the LT recipients complicated with BSI.

Research perspectives

IS reduction may be a generally accepted option in life-threatening infections after LT. However, this practice must be discussed thoroughly, as it seems to be associated with worse outcome in patients with BSI. A multidisciplinary approach, timely and appropriate successful antimicrobial therapy, and source control, when necessary, may be safer and more effective than IS reduction therapy in recipients with BSI after LT.