Drug Resistance and Risk Factors for Acquisition of Gram-Negative Bacteria and Carbapenem-Resistant Organisms Among Liver Transplant Recipients

Abstract

Introduction: Infections caused by Gram-negative bacteria, in particular carbapenem-resistant organisms (CRO), pose a great threat to liver transplant (LT) recipients. Understanding the risk factors for Gram-negative and CRO infections and the drug resistance of corresponding bacteria will help guide the prevention and treatment of these infections.

Methods: Data on the composition, distribution and drug resistance of Gram-negative bacteria and CRO among LT recipients were collected. The risk factors for Gram-negative and CRO infections were identified via univariate and multivariate analysis.

Results: A total of 45 episodes of Gram-negative infection, including 20 episodes of CRO infection, occurred in 19.9% (27/136) of LT recipients. Klebsiella pneumoniae was the dominant pathogenic bacteria (14/45; 31.1%). The most common site of infection was the abdominal cavity/bile duct (11/27; 40.7%). Eleven (8.1%) patients died within 2 months after LT, and two deaths were related to Gram-negative infection. Gram-negative bacteria were relatively sensitive to tigecycline and polymyxin B, with resistance of 26.7 and 11.1%, respectively. CRO had lower resistance to ceftazidime/avibactam (45.5%) and polymyxin B (10%). A univariate analysis showed that male sex, infection within 2 months prior to LT, duration of surgery ≥ 400 min, reoperation, indwelling urethral catheter use ≥ 3 days and elevated alanine aminotransferase on day 1 post-LT were associated with Gram-negative infection. Multivariate logistic regression analysis revealed that infection within 2 months prior to LT [odds ratio (OR) = 4.426, 95%CI: 1.634-11.99, P = 0.003], duration of surgery ≥ 400 min [OR = 3.047, 95%CI: 1.194-7.773, P = 0.02] and indwelling urethral catheter use ≥ 3 days [OR = 5.728, 95%CI: 1.226-26.763, P = 0.026] were independent risk factors for Gram-negative infection after LT, and that only carbapenem use ≥ 3 days within 15 days prior to infection [OR = 14, 95%CI: 1.862-105.268, P = 0.01] was related to the occurrence of CRO infections.

Conclusion: The incidence of Gram-negative and CRO infections was high in the early post-LT period. The most common infection site was the abdominal cavity/bile duct, and the dominant pathogen was K. pneumoniae. Patients with infections within 2 months prior to LT, prolonged surgery time or delayed urethral catheter removal were prone to Gram-negative infection. Carbapenem exposure was correlated with CRO infections.

Keywords: Carbapenem-resistant organism; Drug resistance; Gram-negative infection; Liver transplantation; Risk factors.