The Effect of Host Immunity on Predicting the Mortality of Carbapenem-Resistant Organism Infection.

Qun Lin,Liyan Mao,Yue Wang,Ziyong Sun,Ying Luo,Yicheng Zhang,Guoxing Tang,Feng Wang,Shusheng Li,Weiyong Liu

doi:10.3389/fcimb.2020.00480

Abstract

Carbapenem-resistant organisms (CROs) are associated with considerable mortality clinically. There is a lack of effective tool to predict individual prognosis. We aim to determine if host immunity can be utilized to predict the prognosis of patients infected with CRO. From December 2018 to August 2019, we recruited CRO-infected patients to evaluate risk factors for 30-day mortality. Clinical, routine laboratory, immune and microbiological features were investigated and subjected to univariate and multivariate analyses. The final predictive models were established based on the regression coefficients of multivariate logistic regression. A total of 127 CRO-infected patients were enrolled in our study, including 85 survivors and 42 non-survivors. The number and IFN-γ producing ability of lymphocytes were remarkably decreased in non-survivors. The number of IFN-γ+CD4+ T cells could effectively predict 30-day mortality of CRO infection. Its area under the receiver operating characteristic (ROC) curve, sensitivity, specificity and accuracy, were 0.889 (95% confidence interval [CI], 0.834–0.945), 81.0, 80.0, and 80.3%, respectively. In multivariate analysis of laboratory parameters, IFN-γ+CD4+ T cell number and creatinine concentration were selected for the 2-marker model to predict prognosis fleetly. Its area under the ROC curve, sensitivity, specificity and accuracy were 0.894 (95% CI, 0.841–0.947), 83.3, 82.4, and 82.7%, respectively. Impaired lymphocyte function was an important factor to affect the outcome of CRO-infected patients. A 2-marker model based on the combination of IFN-γ+CD4+ T cell number and creatinine showed good performance in predicting the prognosis of CRO infection.

Highlights

Over the last decade, carbapenem-resistant organisms (CROs), mainly including carbapenemresistant Enterobacteriaceae (CRE), carbapenem-resistant Acinetobacter baumannii (CRAB) and carbapenem-resistant Pseudomonas aeruginosa (CRPsA), have caused serious healthcareassociated infections and disseminated globally (Kizny Gordon et al, 2017; Tomczyk et al, 2019).Host Immunity and CRO InfectionCROs have been highlighted as critical pathogens in the World Health Organization (WHO) prioritization of pathogens (World Health Organization, 2017)
The procedures are shown as following: (1)100 μl of whole blood was diluted with 400 μl of IMDM medium in polystyrene round-bottom tubes with caps (Falcon 352054, Becton Dickinson); (2) the diluted whole blood was incubated in the presence of Leukocyte Activation Cocktail (Becton Dickinson GolgiPlugTM) for 4 h at 37◦C; (3) 300 μl of supernatant was aspirated, cell suspensions were labeled with five kinds of antibodies (Becton Dickinson) and incubated for 15 min at room temperature; (4) the cells were fixed and permeabilized subsequently; (5) the cells were stained with intracellular anti-IFN-γ-APC antibody; and (6) the cells were analyzed with FACSCanto flow cytometer (Becton Dickinson)
There were 68 patients excluded from the study: 25 patients did not fulfill the diagnostic criteria (9 patients failed to meet the imaging criteria and 16 patients failed to meet the sign/symptom criteria); 12 patients missed immunological parameters because of no enough lymphocytes collected for performing lymphocyte function assay; 31 patients were lost to follow-up

Summary

Introduction

Carbapenem-resistant organisms (CROs), mainly including carbapenemresistant Enterobacteriaceae (CRE), carbapenem-resistant Acinetobacter baumannii (CRAB) and carbapenem-resistant Pseudomonas aeruginosa (CRPsA), have caused serious healthcareassociated infections and disseminated globally (Kizny Gordon et al, 2017; Tomczyk et al, 2019).Host Immunity and CRO InfectionCROs have been highlighted as critical pathogens in the World Health Organization (WHO) prioritization of pathogens (World Health Organization, 2017). Due to multiple and high levels of antimicrobial resistance, these bacteria have limited therapeutic options in clinical and resulted in an increased risk of mortality in patients (Falagas et al, 2014; Lemos et al, 2014; Zhang et al, 2016; Agyeman et al, 2020). To identify those at high risk of poor prognosis, it is important to develop effective predictive tools, which may promote a shift from empirical treatment to precision-guided therapy tailored to each patient with expected improved patient outcomes. Lymphocyte function is one of the most important characteristics to reflect host immunity; lymphocyte function assessment has not been widely used in clinical practice (Drabe et al, 2019; Luo et al, 2019)

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