Retrospective Cohort Study
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Mar 27, 2024; 16(3): 379-392
Published online Mar 27, 2024. doi: 10.4254/wjh.v16.i3.379
Comparison of fungal vs bacterial infections in the medical intensive liver unit: Cause or corollary for high mortality?
Sarah Khan, Hanna Hong, Stephanie Bass, Yifan Wang, Xiao-Feng Wang, Omar T Sims, Christine E Koval, Aanchal Kapoor, Christina C Lindenmeyer
Sarah Khan, Department of Internal Medicine, Cleveland Clinic, Cleveland, OH 44195, United States
Hanna Hong, Cleveland Clinic Lerner College of Medicine, Cleveland Clinic, Cleveland, OH 44195, United States
Stephanie Bass, Department of Pharmacy, Cleveland Clinic, Cleveland, OH 44195, United States
Yifan Wang, Xiao-Feng Wang, Department of Quantitative Health Sciences/Biostatistics Section, Cleveland Clinic, Cleveland, OH 44195, United States
Omar T Sims, Christina C Lindenmeyer, Department of Gastroenterology, Hepatology and Nutrition, Cleveland Clinic, Cleveland, OH 44195, United States
Christine E Koval, Department of Infectious Disease, Cleveland Clinic, Cleveland, OH 44195, United States
Aanchal Kapoor, Department of Critical Care Medicine, Cleveland Clinic, Cleveland, OH 44195, United States
Author contributions: All authors were involved in study design; Khan S and Hong H collected data and designed the data collection tool; Khan S, Wang X, Wang Y, Sims O and Lindenmeyer CC were responsible for statistical analysis; Khan S, Bass S, Sims O, Koval C, Kapoor A and Lindenmeyer CC were involved in analysis and interpretation of results of statistical testing; Khan S, Sims O and Lindenmeyer CC were involved in writing the manuscript; all authors were involved in manuscript appraisal and approval.
Institutional review board statement: The study was reviewed and approved by the Cleveland Clinic Foundation Institutional Review Board [IRB# 22-721].
Informed consent statement: Our Institutional Review Board allowed our study to proceed without the need for informed consent.
Conflict-of-interest statement: None of the study authors have any conflicts of interest to disclose.
Data sharing statement: Our statistical code and de-identified data may be made available upon reasonable request.
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: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Sarah Khan, MD, Doctor, Department of Internal Medicine, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, United States. khans21@ccf.org
Received: October 19, 2023
Peer-review started: October 19, 2023
First decision: December 26, 2023
Revised: January 17, 2024
Accepted: February 26, 2024
Article in press: February 26, 2024
Published online: March 27, 2024
Processing time: 153 Days and 23.6 Hours
Abstract
BACKGROUND

Due to development of an immune-dysregulated phenotype, advanced liver disease in all forms predisposes patients to sepsis acquisition, including by opportunistic pathogens such as fungi. Little data exists on fungal infection within a medical intensive liver unit (MILU), particularly in relation to acute on chronic liver failure.

AIM

To investigate the impact of fungal infections among critically ill patients with advanced liver disease, and compare outcomes to those of patients with bacterial infections.

METHODS

From our prospective registry of MILU patients from 2018-2022, we included 27 patients with culture-positive fungal infections and 183 with bacterial infections. We compared outcomes between patients admitted to the MILU with fungal infections to bacterial counterparts. Data was extracted through chart review.

RESULTS

All fungal infections were due to Candida species, and were most frequently blood isolates. Mortality among patients with fungal infections was significantly worse relative to the bacterial cohort (93% vs 52%, P < 0.001). The majority of the fungal cohort developed grade 2 or 3 acute on chronic liver failure (ACLF) (90% vs 64%, P = 0.02). Patients in the fungal cohort had increased use of vasopressors (96% vs 70%, P = 0.04), mechanical ventilation (96% vs 65%, P < 0.001), and dialysis due to acute kidney injury (78% vs 52%, P = 0.014). On MILU admission, the fungal cohort had significantly higher Acute Physiology and Chronic Health Evaluation (108 vs 91, P = 0.003), Acute Physiology Score (86 vs 65, P = 0.003), and Model for End-Stage Liver Disease-Sodium scores (86 vs 65, P = 0.041). There was no significant difference in the rate of central line use preceding culture (52% vs 40%, P = 0.2). Patients with fungal infection had higher rate of transplant hold placement, and lower rates of transplant; however, differences did not achieve statistical significance.

CONCLUSION

Mortality was worse among patients with fungal infections, likely attributable to severe ACLF development. Prospective studies examining empiric antifungals in severe ACLF and associations between fungal infections and transplant outcomes are critical.

Keywords: Fungal, Infection, Sepsis, Acute on chronic liver failure, Intensive care

Core Tip: In the critical care setting, patients with advanced liver disease who develop fungal infections have significantly higher mortality than those who develop bacterial infections. These patients require greater support with vasopressors, mechanical ventilation, and dialysis than their counterparts with bacterial infections. Patients who developed fungal infections appeared more acutely ill on admission to the intensive care unit, with higher Acute Physiology and Chronic Health Evaluation, Acute Physiology Score, and Model for End-Stage Liver Disease scores. In such patients, fungal infection development is closely associated with development of severe acute-on-chronic liver failure. Further work elucidating this relationship will allow for better prognostication and development of predictors for acute on chronic liver failure in this population.