血清PCT、CXCL10、IFN-γ对ICU多重耐药菌感染患者疗效的预测价值

doi:10.11958/20241944

摘要/Abstract

摘要：

目的探究ICU多重耐药菌（MDRO）感染患者降钙素原（PCT）、C-X-C基序趋化因子配体10（CXCL10）和干扰素-γ（IFN-γ）变化及对抗生素治疗效果的预测价值。方法选取重症监护病房（ICU）MDRO感染患者80例为观察组，另择同期ICU未感染患者40例为对照组。观察组患者进行病原菌鉴定和耐药性试验，并评估治疗效果后分为有效组（58例）和无效组（22例）。采用酶联免疫吸附试验（ELISA）测定对照组入组时、观察组确诊MDRO感染时及应用抗生素治疗1周后血清PCT、CXCL10和IFN-γ水平。多因素Logistic回归分析ICU MDRO感染的影响因素。受试者工作特征（ROC）曲线分析血清PCT、CXCL10、IFN-γ治疗前后差值对抗生素治疗效果的预测价值。结果观察组静脉置管时间≥14 d、留置导尿管时间≥14 d比例均高于对照组（P<0.05）。观察组培养出肺炎克雷伯菌、鲍氏不动杆菌、铜绿假单胞菌、大肠埃希菌、金黄色葡萄球菌5种细菌。观察组血清PCT、CXCL10水平高于对照组，IFN-γ水平低于对照组（P<0.05）。血清PCT、CXCL10水平升高、IFN-γ水平降低是ICU MDRO感染的危险因素（P<0.05）。抗生素治疗1周后不同疗效组患者血清PCT、CXCL10水平均较治疗前降低，IFN-γ水平较治疗前升高，且有效患者改善更明显（P<0.05）。血清PCT、CXCL10、IFN-γ治疗前后差值联合对ICU MDRO感染患者抗生素治疗效果的预测价值优于各自单独预测。结论 ICU MDRO感染患者血清PCT、CXCL10升高，IFN-γ水平降低，联合三者治疗前后差值对ICU MDRO感染患者抗生素疗效有较好的预测价值。

关键词: 降钙素原, 趋化因子CXCL10, 干扰素γ, 重症监护病房, 多重耐药菌感染

Abstract:

Objective To investigate expression changes of procalcitonin (PCT), C-X-C motif chemokine ligand 10 (CXCL10) and interferon-γ (IFN-γ) in intensive care unit (ICU) patients with multidrug-resistant bacteria organism (MDRO) infection and their therapeutic guidance value. Methods A total of 80 patients with MDRO infection in ICU were selected as the observation group, and another 40 uninfected patients in ICU during the same period were selected as the control group. The patients in the observation group were divided into the effective group (58 cases) and the ineffective group (22 cases) after identification of pathogenic bacteria and drug resistance test. Enzyme-linked immunosorbent assay (ELISA) was used to determine serum PCT, CXCL10 and IFN-γ levels at the time of the control group was enrolled, at the time of the observation group was diagnosed with MDRO infection and at the time after one week of antibiotic treatment. Multifactorial Logistic regression was used to analyse influencing factors of MDRO infection in ICU. Subject work characteristics (ROC) curves were analysed for the predictive value of the difference between serum PCT, CXCL10 and IFN-γ before and after treatment for the effect of antibiotic treatment. Results The proportion of intravenous catheter placement time≥14 d and indwelling urinary catheter time≥14 d in the observation group was higher than that in the control group (P<0.05). Five types of bacteria were cultured in the observation group including Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Escherichia coli and Staphylococcus aureus. Serum PCT and CXCL10 levels were higher in the observation group than those in the control group, and IFN-γ levels were lower than those in the control group (P<0.05). Elevated serum PCT and CXCL10 levels and reduced IFN-γ levels were risk factors for MDRO infection in ICU (P<0.05). After 1 week of antibiotic treatment, serum PCT and CXCL10 levels were lower in patients in different efficacy groups than those before treatment. IFN-γ levels were higher than before treatment, and the improvement was more obvious in effective patients (P<0.05). The predictive value of the difference between serum PCT, CXCL10 and IFN-γ before and after treatment in combination for the effectiveness of antibiotic treatment in patients with MDRO infection in ICU was better than that of each alone. Conclusion Serum PCT and CXCL10 are elevated and IFN-γ levels are reduced in patients with ICU MDRO infections, and the combined pre- and post-treatment difference between the three has a good predictive value for antibiotic therapy in patients with ICU MDRO infections.

Key words: procalcitonin, chemokine CXCL10, interferon-gamma, intensive care units, multidrug-resistant bacteria organism infection

中图分类号:

R969.3

图/表 6

参考文献 20

[1]	MANGIONI D, CHATENOUD L, COLOMBO J, et al. Multidrug-resistant bacterial colonization and infections in large retrospective cohort of mechanically ventilated COVID-19 patients[J]. Emerg Infect Dis, 2023, 29(8):1598-1607. doi:10.3201/eid2908.230115.
[2]	TROUILLET-ASSANT S, VIEL S, OUZIEL A, et al. Type I interferon in children with viral or bacterial infections[J]. Clin Chem, 2020, 66(6):802-808. doi:10.1093/clinchem/hvaa089.
[3]	LI Y, MIN L, ZHANG X. Usefulness of procalcitonin (PCT),C-reactive protein (CRP),and white blood cell (WBC) levels in the differential diagnosis of acute bacterial,viral,and mycoplasmal respiratory tract infections in children[J]. BMC Pulm Med, 2021, 21(1):386. doi:10.1186/s12890-021-01756-4.
[4]	ALI Z A, MANKHI A A, AD'HIAH A H. Significance of the chemokine CXCL10 and human beta-defensin-3 as biomarkers of pulmonary tuberculosis[J]. Tuberculosis (Edinb), 2021, 128:102078. doi:10.1016/j.tube.2021.102078.
[5]	GAO J, WU L, WANG S, et al. Role of chemokine (C-X-C motif) ligand 10 (CXCL10) in renal diseases[J]. Mediators Inflamm, 2020, 2020:6194864. doi:10.1155/2020/6194864.
[6]	THAMPY L K, REMY K E, WALTON A H, et al. Restoration of T cell function in multi-drug resistant bacterial sepsis after interleukin-7,anti-PD-L1,and OX-40 administration[J]. PLoS One, 2018, 13(6):e0199497. doi:10.1371/journal.pone.0199497.
[7]	LIU W, ZHANG S, WANG J. IFN-γ,should not be ignored in SLE[J]. Front Immunol, 2022, 13:954706. doi:10.3389/fimmu.2022.954706.
[8]	中华人民共和国卫生部. 医院感染诊断标准(试行)[J]. 中华医学杂志, 2001, 81(5):314-320.
	Ministry of Health of the People's Republic of China. Diagnostic criteria for nosocomial infections(proposed)[J]. Natl Med J China, 2001, 81(5):314-320.
[9]	中华医学会呼吸病学分会感染学组. 中国成人医院获得性肺炎与呼吸机相关性肺炎诊断和治疗指南(2018年版)[J]. 中华结核和呼吸杂志, 2018, 41(4):255-280.
	Chinese Medical Association,Respiratory Disease Branch,Infection Group. Guidelines for the diagnosis and treatment of hospital-acquired pneumonia and ventilator-associated pneumonia in Chinese adults (2018 edition)[J]. Chinese Journal of Tuberculosis and Respiratory Diseases, 2018, 41(4):255-280. doi:10.3760/cma.j.issn.1001-0939.2018.04.006.
[10]	SY C L, CHEN P Y, CHENG C W, et al. Recommendations and guidelines for the treatment of infections due to multidrug resistant organisms[J]. J Microbiol Immunol Infect, 2022, 55(3):359-386. doi:10.1016/j.jmii.2022.02.001.
[11]	SCHUETZ P. How to best use procalcitonin to diagnose infections and manage antibiotic treatment[J]. Clin Chem Lab Med, 2022, 61(5):822-828. doi:10.1515/cclm-2022-1072.
[12]	SU W, JU L, HUA Q, et al. Values of combined C-reactive protein,procalcitonin and serum amyloid A in differential diagnosis of bacterial and non-bacterial community acquired pneumonia in children[J]. Diagn Microbiol Infect Dis, 2023, 105(2):115865. doi:10.1016/j.diagmicrobio.
[13]	李琴, 林茜, 刘勤, 等. 2020-2022年儿童下呼吸道细菌感染病原体变迁及血清WBC、PCT、CRP水平分析[J]. 中国病原生物学杂志, 2023, 18(7):835-838,843.
	LI Q, LIN Q, LIU Q, et al. Analysis of changes in bacterial pathogens and serum WBC,PCT,and CRP levels in children with lower respiratory tract infections from 2020 to 2022[J]. Journal of Pathogen Biology, 2023, 18(7):835-838,843. doi:10.13350/j.cjpb.230718.
[14]	MA J, LI L, QIE X, et al. Value of combined detection of PCT,CRP,and FIB in differentiating viral infection from bacterial infection in severe pneumonia[J]. Clin Lab, 2023, 69(11):2247. doi:10.7754/Clin.Lab.2023.230325.
[15]	XU B, HAN L. Predictive value of CRP,PCT and ESR on piperacillin-tazobactam in treating chronic obstructive pulmonary disease with pneumonia[J]. Clin Lab, 2023, 69(4):763. doi:10.7754/Clin.Lab.2022.220640.
[16]	GUDOWSKA-SAWCZUK M, MROCZKO B. What is currently known about the role of CXCL10 in SARS-CoV-2 infection[J]. Int J Mol Sci, 2022, 23(7):3673. doi:10.3390/ijms23073673.
[17]	HIRANI D V, THIELEN F, MANSOURI S, et al. CXCL10 deficiency limits macrophage infiltration,preserves lung matrix,and enables lung growth in bronchopulmonary dysplasia[J]. Inflamm Regen, 2023, 43(1):52. doi:10.1186/s41232-023-00301-6.
[18]	HUANG C, WANG Y, LI X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan,China[J]. Lancet,2020, 395(10223):497-506. doi:10.1016/S0140-6736(20)30183-5.
[19]	KAK G, RAZA M, TIWARI B K. Interferon-gamma (IFN-γ):Exploring its implications in infectious diseases[J]. Biomol Concepts, 2018, 9(1):64-79. doi:10.1515/bmc-2018-0007.
[20]	ZHANG X, ALI M, PANTUCK M A, et al. CD8 T cell response and its released cytokine IFN-γ are necessary for lung alveolar epithelial repair during bacterial pneumonias[J]. Front Immunol, 2023, 14:1268078. doi:10.3389/fimmu.2023.1268078.

组别	n	年龄/岁	性别		BMI/（kg/m²）	入住ICU时间		手术次数		低白蛋白血症
组别	n	年龄/岁	男	女	BMI/（kg/m²）	≥30 d	<30 d	≥2次	<2次	低白蛋白血症
对照组	40	51.18±8.34	22（55.00）	18（45.00）	23.16±1.62	15（37.50）	25（62.50）	14（35.00）	26（65.00）	16（40.00）
观察组	80	51.35±9.28	45（56.25）	35（47.35）	23.32±1.55	36（45.00）	44（55.00）	28（35.00）	52（65.00）	40（50.00）
t或χ²		0.098	0.017		0.525	0.614		0		1.071
组别	呼吸机应用时间				静脉置管时间				留置导尿管时间
组别	≥14 d		<14 d		≥14 d		<14 d		≥14 d	<14 d
对照组	16（40.00）		24（60.00）		10（25.00）		30（75.00）		13（32.50）	27（67.50）
观察组	42（52.50）		38（47.50）		46（57.50）		34（42.50）		55（68.75）	25（31.25）
χ²	1.669				11.317^＊				14.270^＊

组别	n	年龄/岁	性别		BMI/（kg/m²）	入住ICU时间		手术次数		低白蛋白血症
组别	n	年龄/岁	男	女	BMI/（kg/m²）	≥30 d	<30 d	≥2次	<2次	低白蛋白血症
对照组	40	51.18±8.34	22（55.00）	18（45.00）	23.16±1.62	15（37.50）	25（62.50）	14（35.00）	26（65.00）	16（40.00）
观察组	80	51.35±9.28	45（56.25）	35（47.35）	23.32±1.55	36（45.00）	44（55.00）	28（35.00）	52（65.00）	40（50.00）
t或χ²		0.098	0.017		0.525	0.614		0		1.071
组别	呼吸机应用时间				静脉置管时间				留置导尿管时间
组别	≥14 d		<14 d		≥14 d		<14 d		≥14 d	<14 d
对照组	16（40.00）		24（60.00）		10（25.00）		30（75.00）		13（32.50）	27（67.50）
观察组	42（52.50）		38（47.50）		46（57.50）		34（42.50）		55（68.75）	25（31.25）
χ²	1.669				11.317^＊				14.270^＊

组别	n	PCT/（μg/L）	CXCL10/（μg/L）	IFN-γ/（ng/L）
对照组	40	0.32±0.06	62.38±19.26	65.39±18.51
观察组	80	2.98±0.65	95.46±22.15	48.55±12.97
t		25.773^＊	8.043^＊	5.151^＊

组别	n	PCT/（μg/L）	CXCL10/（μg/L）	IFN-γ/（ng/L）
对照组	40	0.32±0.06	62.38±19.26	65.39±18.51
观察组	80	2.98±0.65	95.46±22.15	48.55±12.97
t		25.773^＊	8.043^＊	5.151^＊

变量	B	SE	Wald χ²	P	OR	OR95%CI
PCT	0.491	0.129	14.525	<0.001	1.635	1.269~2.105
CXCL10	0.376	0.180	4.372	0.036	1.457	1.023~2.073
IFN-γ	-0.517	0.223	5.385	0.020	0.596	0.384~0.922
静脉置管时间	0.284	0.252	1.274	0.259	1.329	0.810~2.177
留置导尿管时间	0.117	0.209	0.317	0.573	1.125	0.747~1.695
常数项	1.348	0.412	11.336	<0.001	0.000