gms | German Medical Science

Background: CRE infections in solid organ transplant recipients are associated with high mortality. Studies in this population are limited. The use of Polymyxin B as monotherapy in CRE infections may result in resistance developing against Polymyxin B. Our objectives were to determine the epidemiology, clinical characteristics, risk factors, and outcomes of CRE infections among an Asian liver transplant cohort treated with combination antibiotics.

Methods: A retrospective case-control study was conducted in all transplanted patients between February 2006 and January 2014 to determine risk factors for colonization or infection with CRE. Data were analyzed by multivariable logistic regression using SPSS 17.0. We also compared time from transplant to in-hospital mortality as our primary outcome, between those with CRE versus without CRE.

Results: Seventy-five patients underwent liver transplant (52 males, 23 females). Median age of those without CRE is 60 years old (Range 29-74 year old), with median native Meld score of 16 (Range 15-52). CRE was isolated from six post liver transplant recipients, of whom 33.3% (n=2) and 66.6 % (n=4) were colonized and infected, respectively. Types of CRE include KPC (n=1), NDM-1 (n=1) and non-carbapenemase producing enterobacteriaceae (n=4). Median age for those with CRE is 59 years old (Range 36-68 years old) and median native MELD score is 29 (Range 15-38). Most common cause of liver failure needing liver transplant was Hepatitis B with hepatocellular carcinoma (n=3). Others include Hepatitis B alone (n=1), Alcoholic liver disease (n=1) and Alcoholic liver disease with hepatocellular carcinoma (n=1). The spectrum of infection includes bacteraemia (n=2), surgical wound infection (n=1), and infected intra-abdominal collection (n=1). The combination antibiotics given were Meropenem-Polymyxin B, Imipenem-Tigecycline-Polymyxin B, Amikacin-Meropenem-Polymyxin B and Cefepime-Polymyxin B. The KPC strain developed Polymyxin B resistance. Two (33%) out of six patients died within 2-9 days from acquisition of CRE. Univariate analysis of significant risk factors identified the following factors of acquisition of CRE: living liver transplant donors (OR 7.19; CI 1.2-43.48,p=0.03), length of stay (LOS)(OR 1.04; CI 1.01-1.07, p= 0.001). Multivariable analysis identified only length of stay (OR 1.044, CI 1.006-1.083; p=0.022) as the risk factor of acquisition of CRE. There was a trend suggesting statistical significance in all-cause mortality (p=0.055, log rank test) in liver transplant patients who were CRE infected/colonized as compared to those who were not. Median time from transplant to mortality in patients with CRE was 106 days (Range 39-173) compared to those patients without CRE with a median time to mortality of 195 days (Range 2-1446 days).

Conclusion: Infection due to CRE is infrequent in our LTx recipients and it also results in higher mortality. Combination antibiotics may be necessary to preserve the activity of backbone antibiotic such as Polymyxin B.