Medical Clinic 1, University Hospital, Goethe-University Frankfurt, Frankfurt am Main, Germany.
Liver ICU, Liver Unit, Hospital Clinic, University of Barcelona, IDIBAPS and CIBERehd, Barcelona, Spain.
Aliment Pharmacol Ther. 2024 Apr;59(7):877-888. doi: 10.1111/apt.17899. Epub 2024 Feb 27.
Patients with cirrhosis are susceptible to develop bacterial infections that trigger acute decompensation (AD) and acute-on-chronic liver failure (ACLF). Infections with multidrug-resistant organisms (MDRO) are associated with deleterious outcome. MDRO colonisation frequently proceeds MDRO infections and antibiotic therapy has been associated with MDRO colonisation.
The aim of the study was to assess the influence of non-antibiotic medication contributing to MDRO colonisation.
Three hundred twenty-four patients with AD and ACLF admitted to the ICU of Frankfurt University Hospital with MDRO screening were included. Regression models were performed to identify drugs associated with MDRO colonisation. Another cohort (n = 129) from Barcelona was included to validate. A third multi-centre cohort (n = 203) with metagenomic sequencing data of stool was included to detect antibiotic resistance genes.
A total of 97 patients (30%) were identified to have MDRO colonisation and 35 of them (11%) developed MDRO infection. Patients with MDRO colonisation had significantly higher risk of MDRO infection than those without (p = 0.0098). Apart from antibiotic therapy (odds ratio (OR) 2.91, 95%-confidence interval (CI) 1.82-4.93, p < 0.0001), terlipressin therapy in the previous 14 days was the only independent covariate associated with MDRO colonisation in both cohorts, the overall (OR 9.47, 95%-CI 2.96-30.23, p < 0.0001) and after propensity score matching (OR 5.30, 95%-CI 1.22-23.03, p = 0.011). In the second cohort, prior terlipressin therapy was a risk factor for MDRO colonisation (OR 2.49, 95% CI 0.911-6.823, p = 0.075) and associated with risk of MDRO infection during follow-up (p = 0.017). The validation cohort demonstrated that antibiotic inactivation genes were significantly associated with terlipressin administration (p = 0.001).
Our study reports an increased risk of MDRO colonisation in patients with AD or ACLF, who recently received terlipressin therapy, while other commonly prescribed non-antibiotic co-medications had negligible influence. Future prospective trials are needed to confirm these results.
肝硬化患者易发生细菌感染，从而引发急性失代偿（AD）和慢加急性肝衰竭（ACLF）。多重耐药菌（MDRO）感染与不良结局相关。MDRO 定植通常先于 MDRO 感染，抗生素治疗与 MDRO 定植相关。
本研究旨在评估导致 MDRO 定植的非抗生素药物的影响。
纳入因 MDRO 筛查而入住法兰克福大学医院 ICU 的 324 例 AD 和 ACLF 患者。采用回归模型确定与 MDRO 定植相关的药物。纳入巴塞罗那的另一队列（n=129）进行验证。纳入第三个多中心队列（n=203），进行粪便宏基因组测序数据以检测抗生素耐药基因。
共有 97 例（30%）患者被确定为 MDRO 定植，其中 35 例（11%）发生 MDRO 感染。MDRO 定植患者发生 MDRO 感染的风险显著高于未定植患者（p=0.0098）。除抗生素治疗（比值比（OR）2.91，95%置信区间（CI）1.82-4.93，p<0.0001）外，14 天内使用特利加压素治疗是两个队列中唯一与 MDRO 定植相关的独立协变量，总体（OR 9.47，95%CI 2.96-30.23，p<0.0001）和倾向评分匹配后（OR 5.30，95%CI 1.22-23.03，p=0.011）。在第二个队列中，特利加压素治疗史是 MDRO 定植的危险因素（OR 2.49，95%CI 0.911-6.823，p=0.075），并与随访期间 MDRO 感染的风险相关（p=0.017）。验证队列表明，抗生素失活基因与特利加压素给药显著相关（p=0.001）。
本研究报告称，接受特利加压素治疗的 AD 或 ACLF 患者发生 MDRO 定植的风险增加，而其他常用的非抗生素合并用药影响可忽略不计。需要前瞻性试验来证实这些结果。
