医院获得性细菌性脑膜炎患者预后不良的危险因素分析及列线图预测模型的构建

摘要/Abstract

摘要：

目的：探讨医院获得性细菌性脑膜炎（hospital-acquired bacterial meningitis， HABM）患者预后不良的危险因素，并构建预测其发生的列线图模型。方法：连续纳入开云网页登录医学院附属第六人民医院2013年1月至2020年12月收治的110例医院获得性细菌性脑膜炎患者，根据出院时是否死亡将其分为死亡组（n=22）和生存组（n=88），同时随机将110例患者分为建模组（n=77）和验证组（n=33）。应用最小绝对收缩和选择算子（least absolute shrinkage and selection operator，LASSO）回归及多因素Logistic回归筛选HABM患者预后不良的危险因素，并基于危险因素构建列线图模型，采用受试者操作特征（receiver operating characteristic curve，ROC）曲线的曲线下面积（area under curve，AUC）评估模型区分度，用校准曲线评估模型内部一致性情况。结果：基于LASSO回归共筛选出脑脊液（cerebro-spinal fluid，CSF）微生物培养革兰染色阳性、血常规中性粒细胞计数升高、降钙素原升高、CSF蛋白含量升高、凝血酶原时间缩短、血培养阳性、腰池引流史这7个因素，建立了HABM预后不良列线图预测模型，建模组及验证组ROC曲线的AUC分别为0.931、0.862，校准图显示校准曲线与理想曲线吻合较好，具有良好的拟合优度。结论：本研究构建危险因素列线图模型对住院HABM患者死亡具有较好的预测性、一致性和临床实用性，有助于临床医生对HABM患者预后不良的发生风险进行初步评估。

关键词:脑膜炎,危险因素,预后模型,列线图,最小绝对收缩和选择算子回归

Abstract:

Objective To explore the risk factors for poor prognosis in patients with hospital-acquired bacterial me-ningitis (HABM) and to establish a nomogram model to predict its occurrence.Methods A total of 110 patients with HABM admitted to Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from January 1, 2013 to December 31, 2020 were consecutively enrolled. Based on survival status at discharge, they were divided into a death group (n=22) and a survival group (n=88). Subsequently, 110 patients were randomly divided into a training cohort (n=77) and a validation cohort (n=33). The least absolute shrinkage and selection operator (LASSO) regression and multivariate logistic regression were used to identify risk factors for poor prognosis in patients with HABM. A nomogram model was constructed based on these risk factors. The area under the curve (AUC) of the receiver operating characteristic (ROC) curve was used to evaluate the model discrimination, and the calibration curve was used to evaluate the internal consistency of the model.Results Based on the LASSO regression, seven factors were identified: gram-positive staining of microorga-nisms in cerebro-spinal fluid (CSF) culture, elevated neutrophil count on routine blood tests, elevated procalcitonin, elevated CSF protein, decreased prothrombin time, positive blood culture, and history of lumbar drainage. A nomogram prediction model for poor prognosis in HABM patients was established. The areas under the ROC curves for the training cohort and the validation cohort were 0.931 and 0.862, respectively. The calibration plots demonstrated that the calibration curves showed good agreement with the ideal curves, indicating an excellent goodness of fit.Conclusions The risk factor-based nomogram model established in this study demonstrates good predictability, consistency, and clinical applicability for predicting mortality in hospitalized HABM patients, supporting clinicians in the preliminary assessment of the risk of poor prognosis.

Key words:Meningitis,Risk factor,Prognostic model,Nomogram,Least absolute shrinkage and selection operator regression

中图分类号:

杨梅, 廖啟安, 谭全会, 李婷婷, 张毅, 陈洁, 汤正好. 医院获得性细菌性脑膜炎患者预后不良的危险因素分析及列线图预测模型的构建[J]. 诊断学理论与实践, 2025, 24(04): 441-448.

YANG Mei, LIAO Qi'an, TAN Quanhui, LI Tingting, ZHANG Yi, CHEN Jie, TANG Zhenghao. Analysis of risk factors for poor prognosis in patients with hospital-acquired bacterial meningitis and establishment of nomogram prediction model[J]. Journal of Diagnostics Concepts & Practice, 2025, 24(04): 441-448.

图/表6

表1

生存组与死亡组患者一般资料比较

Characteristics	Death group (n=22)	Survival group (n=88)	P-value	Characteristics	Death group (n=22)	Survival group (n=88)	Pvalue
Age(years)	61 ± 11	55 ± 13	0.057	Antithrombin Ⅲ activity(%)	65 ± 25	89 ± 16	<0.001
Sex(%)			0.483	More than two surgeries(%)			0.212
Female	9 (40.9%)	29 (33.0%)		No	13 (59.1%)	64 (72.7%)
Male	13 (59.1%)	59 (67.0%)		Yes	9 (40.9%)	24 (27.3%)
Admission GCS	7.9 ± 4.0	9.3 ± 3.7	0.073	blood culture（%））			0.001
Gram stain of CSF microbial[n（%）]			0.01	No	11 (50.0%)	73 (83.0%)
Negetive	13 (59.1%)	26 (29.5%)		Yes	11 (50.0%)	15 (17.0%)
Positive	9 (40.9%)	62 (70.5%)		GCS on the day of culture	7.5 ± 3.3	9.4 ± 3.5	0.018
CSF Chloride(mmol/L)	120 ± 17	119 ± 16	0.988	Surgical incision length greater than 10 cm(%)			0.19
CSF Sugar(mmol/L)	2.26 ± 2.13	3.50 ± 2.14	0.02	No	12 (54.5%)	61 (69.3%)
CSF protein(mmol/L)	5.6 ± 5.3	4.2 ± 12.8	0.023	Yes	10 (45.5%)	27 (30.7%)
CSF WBC>10(× 10⁶/L)			0.273	Surgical time greater than 4 h（%）			0.529
<100	12 (54.5%)	59 (67.0%)		No	17 (77.3%)	74 (84.1%)
>100	10 (45.5%)	29 (33.0%)		Yes	5 (22.7%)	14 (15.9%)
CSF RBC[n（%）]			0.775	Tracheal intubation/incision greater than 7 days(%)			0.021
Little	11 (50.0%)	47 (53.4%)		No	3 (13.6%)	35 (39.8%)
Many	11 (50.0%)	41 (46.6%)		Yes	19 (86.4%)	53 (60.2%)
WBC(× 10⁹/L)	14.7 ± 7.2	11.7 ± 5.9	0.07	Fever(%)			0.306
Neutrophil(× 10⁹/L)	12.7 ± 6.7	10.6 ± 15.1	0.037	No	5 (22.7%)	30 (34.1%)
RBC(× 10¹²/L)	3.41 ± 0.57	3.66 ± 0.82	0.199	Yes	17 (77.3%)	58 (65.9%)
PLT(× 10⁹/L)	226 ± 137	278 ± 107	0.019	External ventricular drainage greater than 7 days(%)			0.151
Neutrophil percentage(%)	84 ± 8	77 ± 9	<0.001	No	9 (40.9%)	51 (58.0%)
Lymphocytes(× 10⁹/L)	1.07 ± 0.56	1.31 ± 0.59	0.087	Yes	13 (59.1%)	37 (42.0%)
Monocytes(× 10⁹/L)	0.76 ± 0.42	0.81 ± 0.53	0.994	CSF leakage(%)			0.684
Average platelet volume(fL)	11.41 ± 1.62	10.52 ± 1.09	0.02	No	21 (95.5%)	80 (90.9%)
Platelet mean width(fL)	15.19 ± 3.80	13.77 ± 11.10	0.005	Yes	1 (4.5%)	8 (9.1%)
Plateletcrit(%)	0.25 ± 0.13	0.29 ± 0.11	0.087	Extraspinal diversion(%)			0.049
Albumin (g/L)	33.2 ± 5.3	36.3 ± 4.8	0.002	No	18 (81.8%)	84 (95.5%)
Albumin to globulin ratio	1.48 ± 0.41	1.51 ± 0.36	0.403	Yes	4 (18.2%)	4 (4.5%)
CRP（mg/L）	79 ± 38	56 ± 47	0.003	V-P shunting(%)			0.755
Procalcitonin（ng/mL）	1.40 ± 1.83	0.32 ± 0.38	<0.001	No	18 (81.8%)	74 (84.1%)
D-D（mg/L）	4.1 ± 4.3	4.1 ± 4.1	0.799	Yes	4 (18.2%)	14 (15.9%)
PT(s)	14.19 ± 2.06	12.26 ± 1.31	<0.001	Diplopneumonia(%)			0.09
INR	1.69 ± 2.10	1.07 ± 0.12	<0.001	No	3 (13.6%)	28 (31.8%)
APTT（s）	38 ± 15	29 ± 7	0.003	Yes	19 (86.4%)	60 (68.2%)
Fibrinogen(g/L)	3.97 ± 1.54	4.00 ± 2.14	0.893	Deep vein cannulation(%)			0.017
Prothrombin time（s）	16.84 ± 2.28	16.30 ± 1.85	0.168	No	2 (9.1%)	31 (35.2%)
FDP(mg/L)	13 ± 12	13 ± 11	0.751	Yes	20 (90.9%)	57 (64.8%)

表1

表2

建模组与验证组患者临床资料比较

Characteristic	Cohort		P-value	Characteristic	Cohort		Pvalue
Characteristic	Training Cohort (n=77)	Internal Test Cohort (n=33)	P-value	Characteristic	Training Cohort (n=77)	Internal Test Cohort (n=33)	Pvalue
Age(years)	57 ± 12	55 ± 14	0.524	Extraspinal diversion(%)			0.431
Sex(%)			0.861	No	70 (90.9%)	32 (97.0%)
Female	27 (35.1%)	11 (33.3%)		Yes	7 (9.1%)	1 (3.0%)
Male	50 (64.9%)	22 (66.7%)		CSF leakage(%)			0.448
Gram stain of CSF microbial			0.317	No	72 (93.5%)	29 (87.9%)
Negetive	25 (32.5%)	14 (42.4%)		Yes	5 (6.5%)	4 (12.1%)
Positive	52 (67.5%)	19 (57.6%)		V-P shunting(%)			0.043
CSF Chloride(mmol/L)	119 ± 18	119 ± 12	0.834	No	68 (88.3%)	24 (72.7%)
CSF Sugar(mmol/L)	3.55 ± 2.33	2.56 ± 1.64	0.013	Yes	9 (11.7%)	9 (27.3%)
CSF protein(mmol/L)	5.0 ± 13.7	3.3 ± 3.6	0.32	Diplopneumonia(%)			0.432
CSF RBC(%)			0.56	No	20 (26.0%)	11 (33.3%)
Little	42 (54.5%)	16 (48.5%)		Yes	57 (74.0%)	22 (66.7%)
Many	35 (45.5%)	17 (51.5%)		Deep vein cannulation(%)			0.159
CSF WBC(× 10⁶/L)			0.896	No	20 (26.0%)	13 (39.4%)
<100	50 (64.9%)	21 (63.6%)		Yes	57 (74.0%)	20 (60.6%)
>100	27 (35.1%)	12 (36.4%)		WBC(× 10⁹/L)	13.1 ± 6.6	10.5 ± 5.3	0.033
Admission GCS	9.1 ± 3.8	8.9 ± 3.7	0.786	Neutrophil(× 10⁹/L)	12.2 ± 16.2	8.3 ± 4.6	0.053
Blood culture(%)			0.281	Neutrophil percentage(%)	78 ± 10	78 ± 7	0.626
Negetive	61 (79.2%)	23 (69.7%)		Monocytes(× 10⁹/L)	0.84 ± 0.54	0.71 ± 0.43	0.175
Positive	16 (20.8%)	10 (30.3%)		Lymphocytes(× 10⁹/L)	1.27 ± 0.59	1.27 ± 0.59	0.998
More than two surge-ries(%)			0.159	PLT(× 10⁹/L)	243 ± 117	240± 120	0.164
No	57 (74.0%)	20 (60.6%)		Plateletcrit(%)	0.26 ± 0.12	0.30 ± 0.15	0.876
Yes	20 (26.0%)	13 (39.4%)		Albumin to globulin ratio	11.39 ± 1.6	10.59 ± 1.15	0.335
GCS on the day of culture	8.9 ± 3.5	9.2 ± 3.5	0.723	CRP（mg/L）	81 ± 41	82 ± 23	0.445
Surgical incision length greater than 10 cm(%)			0.692	Procalcitonin（ng/mL）	0.92 ± 0.8	1.2 ± 0.9	0.126
No	52 (67.5%)	21 (63.6%)		Average platelet volume(fL)	10.82 ± 1.24	10.41 ± 1.26	0.118
Yes	25 (32.5%)	12 (36.4%)		Platelet mean width(fL)	13.23 ± 2.84	15.96 ± 17.91	0.391
Surgical time greater than 4 h			0.7	RBC(× 10¹²/L)	3.66 ± 0.85	3.48 ± 0.57	0.205
No(%)	63 (81.8%)	28 (84.8%)		Albumin (g/L)	35.5 ± 4.9	36.2 ± 5.3	0.534
Yes	14 (18.2%)	5 (15.2%)		Fibrinogen(g/L)	4.09 ± 2.17	3.77 ± 1.68	0.405
Tracheal intubation/ incision greater than 7 days(%)			0.793	APPT(s)	30 ± 10	31 ± 10	0.669
No	26 (33.8%)	12 (36.4%)		INR	1.23 ± 1.14	1.11 ± 0.15	0.376
Yes	51 (66.2%)	21 (63.6%)		Prothrombin time(s)	12.59 ± 1.65	12.78 ± 1.74	0.596
Fever(%)			0.823	D-D(mg/L)	4.2 ± 4.3	4.1 ± 3.7	0.908
No	25 (32.5%)	10 (30.3%)		PT(s)	16.24 ± 1.72	16.80 ± 2.36	0.228
Yes	52 (67.5%)	23 (69.7%)		FDP(mg/L)	13 ± 12	14 ± 10	0.91
External ventricular drainage greater than 7 days(%)			>0.999	Antithrombin Ⅲ activity(%)	86 ± 19	80 ± 23	0.226
No	42 (54.5%)	18 (54.5%)		Proealeitonin(ng/mL)	275 ± 119	252 ± 105	0.332
Yes	35 (45.5%)	15 (45.5%)

表2

图1

表 3

图2

图3

参考文献17

[1]	HASBUN R. Progress and challenges in bacterial meningitis: a review[J].JAMA,2022,328(21):2147-2154. doi:10.1001/jama.2022.20521pmid:36472590
[2]	LI Z, YANG W, YE X, et al. Early intraventricular anti-biotic therapy improved in-hospital-mortality in neurocritical patients with multidrug-resistant bacterial nosocomial meningitis and ventriculitis[J].Neurocrit Care,2024,40(2):612-620.
[3]	ZHANG Y, XIAO X, ZHANG J, et al. Diagnostic accuracy of routine blood examinations and CSF lactate level for post-neurosurgical bacterial meningitis[J].Int J Infect Dis,2017,59:50-54. doi:S1201-9712(17)30111-Xpmid:28392319
[4]	VAN DE BEEK D, CABELLOS C, DZUPOVA O, et al. ESCMID guideline: diagnosis and treatment of acute bacterial meningitis[J].Clin Microbiol Infect,2016,22(Suppl 3): S37-62.
[5]	姜秀国, 王辉, 顾明, 等. 成人社区获得性单核细胞增生李斯特菌脑膜炎[J].中华急诊医学杂志,2012,21(10):1140-1146.
	JIANG X G, WANG H, GU M, et al. Community acquired Listeria monocytogenes meningitis in adults[J].Chin J Emerg Med,2012,21(10):1140-1146.
[6]	TSAI M H, LU C H, HUANG C R, et al. Bacterial meningitis in young adults in Southern Taiwan: clinical characteristics and therapeutic outcomes[J].Infection,2006,34(1):2-8. doi:10.1007/s15010-006-4144-6pmid:16501895
[7]	WEISFELT M, VAN DE BEEK D, SPANJAARD L, et al. A risk score for unfavorable outcome in adults with bacterial meningitis[J].Ann Neurol,2008,63(1):90-97. pmid:17823938
[8]	VIBHA D, BHATIA R, PRASAD K, et al. Clinical features and independent prognostic factors for acute bacterial meningitis in adults[J].Neurocrit Care,2010,13(2):199-204. doi:10.1007/s12028-010-9396-4pmid:20577910
[9]	刘子林, 肖绍武, 叶琳, 等. 结核性脑膜炎患者预后情况调查及其相关影响因素分析[J].中国医学创新,2021,18(35):69-72.
	LIU Z L, XIAO S W, YE L, et al. Investigation of prognosis of tuberculous meningitis patients and analysis of related influencing factors[J].Med Innov China,2021,18(35):69-72.
[10]	李承, 孙丹, 王晶, 等. 90例儿童化脓性脑膜炎病原学及临床表现和预后[J].中华医院感染学杂志,2022,32(18):2856-2859.
	LI C, SUN D, WANG J, et al. Etiological characteristics,clinical manifestations and prognosis of 90 children with purulent meningitis[J].Chin J Nosocomiol,2022,32(18):2856-2859.
[11]	CHAKRABARTI P, DAS B K, KAPIL A. Application of 16S rDNA based seminested PCR for diagnosis of acute bacterial meningitis[J].Indian J Med Res,2009,129(2):182-188. pmid:19293446
[12]	VASILOPOULOU V A, KARANIKA M, THEODORIDOU K, et al. Prognostic factors related to sequelae in childhood bacterial meningitis: data from a Greek meningitis registry[J].BMC Infect Dis,2011,11:214. doi:10.1186/1471-2334-11-214pmid:21827712
[13]	刘梦迪, 徐发林, 段稳丽, 等. 新生儿细菌性脑膜炎预后不良的危险因素分析[J].中国当代儿科杂志,2019,21(11):1064-1068.
	LIU M D, XU F L, DUAN W L, et al. Risk factors for poor prognosis of neonatal bacterial meningitis[J].Chin J Contemp Pediatr,2019,21(11):1064-1068.
[14]	李海燕, 李君莲, 吴倩, 等. 结核性脑膜炎患者预后不良的危险因素分析及列线图预测模型的构建[J].中华神经医学杂志,2023,22(9):891-898.
	LI H Y, LI J L, WU Q, et al. Risk factors for poor prognosis in patients with tuberculous meningitis and establishment of their nomogram predictive models[J].Chin J Neurol,2023,22(9):891-898.
[15]	MEYFROIDT G, KURTZ P, SONNEVILLE R. Critical care management of infectious meningitis and encephalitis[J].Intensive Care Med,2020,46(2):192-201. doi:10.1007/s00134-019-05901-wpmid:31938828
[16]	CITERIO G, SIGNORINI L, BRONCO A, et al. External ventricular and lumbar drain device infections in ICU patients: a prospective multicenter Italian study[J].Crit Care Med,2015,43(8):1630-1637. doi:10.1097/CCM.0000000000001019pmid:25867904
[17]	RAMANAN M, LIPMAN J, SHORR A, et al. A meta-analysis of ventriculostomy-associated cerebrospinal fluid infections[J].BMC Infect Dis,2015,15:3. doi:10.1186/s12879-014-0712-zpmid:25567583