医院获得性肺炎患者肺炎克雷伯菌多部位感染的临床特征及毒力基因分布

doi:10.19723/j.issn.1671-167X.2026.01.027

摘要/Abstract

摘要：

目的: 分析医院获得性肺炎患者肺炎克雷伯菌(Klebsiella pneumoniae)多部位感染的临床特征和毒力基因特征, 以及多部位感染患者30 d内死亡的危险因素, 为临床抗感染治疗提供帮助。方法: 选择北京大学第三医院2018年3月至2023年6月痰培养中分离出肺炎克雷伯菌的医院获得性肺炎患者的病例资料进行回顾性分析, 共连续纳入患者128例, 其中多部位感染组35例, 单纯肺部感染组93例, 分析并比较两组患者的临床资料、菌株序列分型及毒力相关基因。结果: 两组患者年龄、性别、住院时长≥30 d患者比例、90 d内抗菌药物暴露率、30 d死亡率差异均有统计学意义(P均＜0.05), 两组患者合并间质性肺病、心肌梗死、周围血管病、消化性溃疡、糖尿病、偏瘫比例差异亦有统计学意义(P均＜0.05)。多部位感染组格拉斯哥昏迷评分(Glasgow coma scale, GCS)＜8分、行外周静脉置入中心静脉导管(peripherally inserted central catheter, PICC)及胃管侵入操作、出现胸腔积液和感染性休克患者比例均显著高于单纯肺部感染组(P＜0.05);血液降钙素原(procalcitonin, PCT)水平显著高于单纯肺部感染组(P=0.004), 血红细胞计数、血红蛋白水平显著低于单纯肺部感染组(P＜0.001);肺炎克雷伯菌菌株中ST11型占比及iroB、ybtA、irp1、fyuA毒力基因检出率均显著高于单纯肺部感染组(P＜0.05)。根据是否出现30 d内死亡将多部位感染组患者进一步分为多部位感染生存组(n=21)和死亡组(n=14), 多因素分析表明感染性休克是多部位感染30 d内死亡的独立危险因素(P=0.045, OR=38.510)。结论: 肺炎克雷伯菌多部位感染的患者多见于高龄、女性, 多有基础疾病史、侵入性操作史及90 d内抗菌药物暴露史, 且具有更低的红细胞计数、血红蛋白水平及更高的PCT水平, 易出现胸腔积液、感染性休克; 感染性休克是肺炎克雷伯菌多部位感染患者30 d内死亡的独立危险因素; 致多部位感染的菌株中以ST11型为主, iroB、ybtA、irp1、fyuA基因携带率更高。

关键词: 医院获得性肺炎, 肺炎克雷伯菌, 毒力, 细菌基因, 多部位感染

Abstract:

Objective: To analyze the clinical features and virulence gene characteristics of Klebsiella pneumoniae multi-site infections in patients with hospital-acquired pneumonia, as well as the risk factors for death within 30 days in patients with multi-site infections, in order to provide help for clinical anti-infective treatment. Methods: The case data of hospital-acquired pneumonia patients with Klebsiella pneumoniae isolated in sputum culture from March 2018 to June 2023 in Peking University Third Hospital were selected for retrospective analysis, and a total of 128 consecutive patients were enrolled, of whom 35 were in the multi-site infection group and 93 were in the lung infection group, and the clinical data, strain sequence typing, and virulence-related genes of the patients in the two groups were analyzed and compared. Results: The differences in age, gender, proportion of the patients with length of hospital stay ≥30 days, antibiotic exposure rate within 90 days and 30-day mortality rate between the two groups were statistically significant (all P < 0.05); the differences in the proportions of combined interstitial lung disease, myocardial infarction, peripheral vascular disease, peptic ulcer, diabetes mellitus and hemiplegia between the two groups were statistically significant (all P < 0.05). The proportions of patients with Glasgow coma scale (GCS) scores < 8 points, the proportion of the patients who underwent peripherally inserted central catheter (PICC) and gastric tube invasive operation, the proportion of the presence of pleural effusion and infectious shock in the multi-site infection group were significantly higher than those of the pulmonary infection group (all P < 0.05). The blood procalcitonin (PCT) level in the multi-site infection group was significantly higher than that of the pulmonary infection group (P=0.004), and the red blood cell count and hemoglobin level were significantly lower than those of the pulmonary infection group (P < 0.001). The proportion of ST11 and the detection rates of virulence genes iroB, ybtA, irp1 and fyuA in Klebsiella pneumoniae strains in the multi-site infection group were significantly higher than those in the pulmonary infection group (P < 0.05). According to the occurrence of death within 30 days, the patients in the multi-site infection group were further divided into the multi-site infection survival group (n=21) and the non-survival group (n=14). Multivariate analysis showed that septic shock was an independent risk factor for death within 30 days of multi-site infection (P=0.045, OR=38.510). Conclusion: Patients with Klebsiella pneumoniae multi-site infection were mainly found in patients with advanced age, female, more comorbidities, performing invasive operation and having history of antimicrobial drug exposure within 90 days. They had lower erythrocyte counts, hemoglobin levels and higher PCT levels, and were prone to pleural effusion, infectious shock. Infectious shock was an independent risk factor for death within 30 days in patients with Klebsiella pneumoniae multi-site infection. ST11 type was the most prevalent type of multi-site infectious strains, and the virulence genes iroB, ybtA, irp1, fyuA were more prevalent.

Key words: Hospital-acquired pneumonia, Klebsiella pneumoniae, Virulence, Bacterial genes, Multi-site infection

中图分类号:

R563.11

耿芸玲, 刘超, 杨萍, 郑佳佳, 沈宁, 杜毅鹏. 医院获得性肺炎患者肺炎克雷伯菌多部位感染的临床特征及毒力基因分布[J]. 北京大学学报（医学版）, 2026, 58(1): 201-207.

Yunling GENG, Chao LIU, Ping YANG, Jiajia ZHENG, Ning SHEN, Yipeng DU. Clinical features and virulence gene distribution of Klebsiella pneumoniae multi-site infection in patients with hospital-acquired pneumonia[J]. Journal of Peking University (Health Sciences), 2026, 58(1): 201-207.

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Items	Multi-site infection group (n=35)	Lung infection group (n=93)	Z/χ²	P
Age/years	85 (82, 88)	79 (69, 85)	2.513	0.012
Sex (male/female)	15/20	67/26	9.409	0.002
Length of hospitalization ≥30 d	29 (82.9)	35 (37.6)	20.802	< 0.001
Admission to intensive care unit	24 (68.6)	59 (63.4)	0.221	0.638
History of antimicrobial exposure within 90 d	34 (97.1)	75 (80.6)	5.476	0.019
30-day mortality	14 (40.0)	14 (15.1)	9.260	0.002
Distribution of specimens
Sputum and pulmonary alveolar lavage fluid	35 (100.0)	93 (100.0)
Urine	19 (54.3)	0 (0)
Blood	13 (37.1)	0 (0)
Surgical wound discharge	2 (5.7)	0 (0)
Ascites	1 (2.9)	0 (0)
Distribution of departments
Intensive care unit	20 (57.1)	36 (38.7)	3.511	0.061
Emergency department ward	7 (20.0)	7 (7.5)	2.882	0.090
Respiratory medicine department	1 (2.9)	16 (17.2)	3.385	0.066
Other internal medicine wards	6 (17.1)	21 (22.6)	0.452	0.501
Other surgical wards	1 (2.9)	13 (14.0)	2.188	0.139

Items	Multi-site infection group (n=35)	Lung infection group (n=93)	P
Amoxicillin / Clavulanate	22 (73.3)	34 (47.2)	0.016
Piperacillin / Tazobactam	27 (79.4)	37 (42.0)	< 0.001
Cefatriaxone	27 (79.4)	43 (49.4)	0.003
Cefepime	28 (80.0)	42 (45.7)	0.001
Ceftazidime	28 (80.0)	42 (45.7)	0.001
Ceftazidime / Avibactam	13 (37.1)	1 (1.8)	< 0.001
Cefoperazone / Sulbactam	25 (71.4)	39 (41.9)	0.003
Levofloxacin	28 (80.0)	42 (45.7)	0.001
Ciprofloxacin	28 (82.4)	44 (51.2)	0.002
Minocycline	14 (40.0)	23 (25.0)	0.096
Doxycycline	10 (37.0)	19 (29.2)	0.463
Tigecycline	0 (0)	0 (0)
Meropenem	22 (62.8)	33 (36.3)	0.007
Imipenem	22 (62.8)	34 (37.0)	0.009
Ertapenem	20 (57.1)	35 (38.5)	0.058
Amikacin	18 (51.4)	22 (23.9)	0.003
Aztreonam	19 (73.1)	30 (43.5)	0.010
Cotrimoxazole	12 (34.2)	30 (32.6)	0.858
Colistin	4 (16.0)	1 (1.6)	0.024
Tobramycin	14 (53.8)	18 (26.5)	0.012

Items	Multi-site infection group (n=35)	Lung infection group (n=93)	χ²	P
Comorbidities
Interstitial lung disease	5 (14.3)	3 (3.2)	5.309	0.021
Myocardial infarction	9 (25.7)	6 (6.5)	9.121	0.003
Peripheral vascular disease	19 (54.3)	14 (15.1)	20.455	< 0.001
Peptic ulcer	17 (48.6)	1 (1.1)	47.469	< 0.001
Diabetes mellitus	1 (2.9)	33 (35.5)	13.877	< 0.001
Hemiplegia	13 (37.1)	1 (1.1)	33.960	< 0.001
Disease severity score
CCI score>4	8 (22.9)	9 (9.7)	3.835	0.076
GCS score < 8	15 (42.9)	16 (17.2)	9.118	0.003
Invasive procedures
CVC	18 (51.4)	40 (43.0)	0.727	0.394
PICC	15 (42.9)	11 (11.8)	15.126	< 0.001
Catheter	29 (82.9)	6 (17.1)	0.175	0.676
Tracheal intubation	13 (37.1)	29 (31.2)	0.410	0.522
Gastric tube	32 (91.4)	62 (66.7)	7.993	0.005
Drainage tube	7 (20.0)	17 (18.3)	0.049	0.824
Complications
Pleural effusion	21 (60.0)	36 (38.7)	4.667	0.031
Infectious shock	13 (37.1)	8 (8.6)	15.104	< 0.001
Respiratory failure	14 (40.0)	39 (41.9)	0.039	0.843

Items	Multi-site infection group (n=35)	Lung infection group (n=93)	t/Z	P
WBC/(×10⁹/L)	8.94 (6.88, 12.13)	9.44 (6.28, 14.25)	1.251	0.211
RBC/(×10¹²/L)	2.94±0.68	3.64±0.82	4.595	< 0.001
HB/(g/L)	89.17±19.91	110.74±25.50	4.799	< 0.001
HCT	0.28±0.07	0.34±0.08	0.438	0.662
PLT/(×10⁹/L)	195.17±114.03	207.91±96.68	1.842	0.068
NEUT/%	80.65 (69.25, 87.75)	78.45 (70.73, 83.80)	1.756	0.079
NEUT/(×10⁹/L)	6.36 (4.81, 10.30)	7.51 (4.39, 12.11)	1.016	0.310
TB/(μmol/L)	13.25 (10.10, 17.03)	12.70 (8.93, 24.63)	0.380	0.704
Cr/(μmol/L)	69.00 (37.00, 179.50)	72.50 (48.50, 98.50)	0.527	0.598
ALB/(g/L)	32.70 (29.35, 36.25)	32.15 (28.36, 35.45)	0.782	0.434
ALT/(U/L)	19.00 (13.00, 36.75)	22.50 (12.75, 42.50)	0.354	0.724
AST/(U/L)	29.00 (22.00, 37.75)	26.00 (19.00, 43.00)	1.261	0.207
ALP/(U/L)	117.00 (76.25, 141.25)	89.50 (71.75, 128.25)	1.450	0.147
PCT/(μg/L)	0.27 (0.13, 2.61)	0.11 (0.05, 0.50)	2.887	0.004
PT/s	12.90 (11.18, 14.85)	12.40 (11.48, 14.23)	0.830	0.407
INR	1.21 (1.04, 1.38)	1.15 (1.07, 1.32)	0.788	0.431
D-dimer/(mg/L)	0.71 (0.42, 1.23)	0.68 (0.28, 1.49)	1.677	0.094
HbA1C/%	6.07±0.75	6.34±0.72	0.312	0.756
FBG/(mmol/L)	5.79 (5.23, 7.54)	6.10 (5.60, 7.20)	0.538	0.591

Items	Multi-site infection group (n=35)	Lung infection group (n=93)	χ²	P
Sequence typing			6.616	0.01
ST11	20 (57.1)	30 (32.3)
Non-ST11	15 (42.9)	63 (67.7)
Virulence genes
iucA	19 (54.3)	40 (43.0)	1.301	0.254
iroB	6 (17.1)	36 (38.7)	5.365	0.021
rmpA	9 (25.7)	38 (40.9)	2.511	0.113
rmpA2	16 (45.7)	36 (38.7)	0.517	0.472
peg-344	9 (25.7)	39 (41.9)	2.855	0.091
ybtA	30 (85.7)	61 (65.6)	5.011	0.025
irp1	30 (85.7)	61 (65.6)	5.011	0.025
fyuA	30 (85.7)	61 (65.6)	5.011	0.025
String test	12 (34.3)	28 (30.1)	0.207	0.649
hvKP	22 (62.9)	62 (66.7)	0.164	0.686