ICU病人耐碳青霉烯类肺炎克雷伯菌血流感染的危险因素与预后分析（附81例报告）

doi:10.16139/j.1007-9610.2023.05.11

摘要/Abstract

摘要：

目的：分析真实世界中重症病人耐碳青霉烯类肺炎克雷伯菌血流感染(carbapenem-resistant Klebsiella pneumonia bloodstream infection, CRKP-BSI)的死亡危险因素以及治疗效果，为病人个体化治疗提供参考。方法：回顾性分析2016年7月至2020年6月我院重症监护病房内81例CRKP-BSI病人的临床特征，评估死亡危险因素及不同抗菌药物方案的治疗效果。结果：CRKP-BSI以腹腔来源和呼吸道来源的占比较多，分别为56.79%（46例）、22.22%（18例）。CRKP-BSI病人28 d死亡率及住院死亡率分别为54.32%（44例）、65.43%（53例）。多因素回归分析结果提示入院前患胆道疾病（P=0.026）、病人BSI发生时SOFA评分升高（P=0.006）为28 d死亡率独立危险因素。接受以替加环素为基础（44例）或以多黏菌素B（26例）为基础的抗生素治疗，两组28 d死亡率差异无统计学意义[56.82%(25/44)比57.69%(15/26), P=0.943]。根据病人的年龄（≤65岁比>65岁）、性别、体质量指数（≤25 kg/m²比 >25 kg/m²）、APACHE Ⅱ评分（≤20分比>20分）、肾脏替代治疗及机械通气的使用分为不同亚组，各亚组间死亡率差异无统计学意义。结论：SOFA评分及入院前胆道疾病病史是CRKP-BSI 28 d死亡率的危险因素。以替加环素为基础与以多黏菌素B为基础的抗菌药物治疗效果无差异。

关键词: 耐碳青霉烯类肺炎克雷伯菌, 血流感染, 重症病人

Abstract:

Objective Comprehensive mortality risk analyses and therapeutic assessment in real-world practice are beneficial to guide individual treatment in patients with Carbapenem-resistant Klebsiella pneumoniae bloodstream infections (CRKP-BSI). Methods Retrospective analysis of the clinical characteristics of 81 CRKP-BSI patients in our intensive care unit from July 2016 to June 2020, to indentify the risk factors of death and treatment effects of different antibiotic regimens. Results In 81 CRKP-BSI cases, the majority source were from abdominal and respiratory, accounting for 56.79% (46 cases) and 22.22% (18 cases), respectively. The 28-day mortality and hospitalization mortality of CRKP-BSI were 54.32% (44 cases) and 65.43% (53 cases). Multivariate regression analysis suggested that biliary tract disease before admission (P=0.026) and increased SOFA score at the onset of BSI (P=0.006) were independent risk factors for 28-day mortality. There was no statistically significant difference in 28-day mortality between the groups of antibiotic treatment based on tigecycline (44 cases) and polymyxin B (26 cases) [56.82% (25/44) vs. 57.69% (15/26), P=0.943]. Patients were evaluated based on their age (≤ 65 years vs. >65 years), gender, body mass index (≤25 kg/m² vs. >25 kg/m²), and APACHE Ⅱ score (≤20 vs. >20), the use of renal replacement therapy and mechanical ventilation, there was no difference in the mortality among each subgroup. Conclusions Biliary tract disease before admission and SOFA score were independent risk factors for 28-day mortality. There was no significant difference outcomes between tigecycline- and polymyxin B-based therapy.

Key words: Carbapenem-resistant Klebsiella pneumoniae, Bloodstream infection, Critically ill patient

中图分类号:

刘萌, 徐文, 戴赟麒, 谭若铭, 刘嘉琳, 顾飞飞, 陈尔真, 王晓丽, 瞿洪平, 邱毓祯. ICU病人耐碳青霉烯类肺炎克雷伯菌血流感染的危险因素与预后分析（附81例报告）[J]. 外科理论与实践, 2023, 28(05): 454-462.

LIU Meng, XU Wen, DAI Yunqi, TAN Ruoming, LIU Jialin, GU Feifei, CHEN Erzhen, WANG Xiaoli, QU Hongping, QIU Yuzhen. Risk factors and prognosis of carbapenem-resistant Klebsiella pneumoniae bloodstream infection in ICU patients: a report of 81 cases[J]. Journal of Surgery Concepts & Practice, 2023, 28(05): 454-462.

图/表 6

表1

病人临床特征及CRKP-BSI危重病人28 d全因死亡率相关因素分析[$\bar{x} \pm s$/M(P25，P75)/n(%)]

Item	Total(n=81)	Non-surviver(n=44)	Surviver(n=37)	t/Z/χ² value	P value
Demographic variable
Age (years)	58.12±17.52	62.73±14.66	52.65±19.20	2.68	0.009^a）
Male sex [n(%)]	63 (77.78)	32(72.72)	31(83.78)	1.42	0.233^b）
BMI (kg/m²)	23.88(21.83, 27.63)	24.79(18.62, 30.96)	23.67(22.07, 27.32)	791	0.827^b）
NRS-2002	6(4, 6)	6(4, 6)	5(4, 6)	675	0.170^b）
Comorbidity
Charlson comorbidity score	2(1,4)	3(1, 4)	2(0, 6)	674	0.178^b）
Diabetes mellitus [n(%)]	24(19.63)	12(27.27)	12(32.43)	0.26	0.612^c）
Chronic renal failure [n(%)]	8(9.88)	3(6.82)	5(13.51)	0.40	0.527^c）
Chronic liver diseases [n(%)]	1(1.23)	1(2.27)	0(0)	-	1^c）
Biliary tract disease [n(%)]	10(12.35)	9(20.45)	1(2.7)	4.33	0.038^c）
Congestive heart failure [n(%)]	2(2.47)	2(4.55)	0(0)	-	0.498^c）
COPD [n(%)]	5(6.17)	3(6.82)	2(4.88)	0	1^c）
Malignancy [n(%)]	13(16.05)	7(15.91)	6(16.22)	0.00	0.97^c）
Immunosupressiono [n(%)]	8(9.88)	3(6.82)	5(13.51)	0.4.	0.527^c）
Health-care exposure before hospitalization
Antibiotic exposure (< 30 d) [n(%)]	53(65.43)	26(59.09)	27(70.97)	1.71	0.191^c）
ICU admission(< 30 d) [n(%)]	31(38.27)	13(29.55)	18(48.65)	3.11	0.078^c）
Surgery(< 30 d) [n(%)]	16(19.75)	7(15.91)	9(24.32)	0.90	0.343^c）
Immunosuppressive therapy (< 3 m) [n(%)]	9(11.11)	3(6.82)	6(16.22)	0.97	0.324^c）
Previous hospitalization (< 12 m) [n(%)]	47(58.02)	26(59.09)	21(56.76)	0.05	0.832^c）
Length of stay before BSI	23.00(13.00, 36.00)	23.50(14.25, 39.50)	23(9.00, 33.50)	755	0.576^b）
Source of infection [n(%)]
Central line	8(9.88)	4(9.09)	4(10.81)	0.00	1^c）
Urinary tract	2(2.47)	1(2.27)	1(2.70)	-	1^c）
Intra-abdominal	46(56.79)	24(54.55)	22(59.46)	0.20	0.657^c）
Respiratory	18(22.22)	11(25.00)	7(18.92)	0.43	0.512^c）
Skin and soft tissue	3(3.70)	2(4.55)	1(2.70)	0.00	1^c）
Cardio-vascular system infection	1(1.23)	1(2.27)	0	-	1^c）
Primary	3(3.70)	1(2.27)	2(5.41)	0.02	0.878^c）
Severity of illness at BSI onset
Biomarker at BSI onset
PCT (ng/L)	2.99(0.77, 7.95)	3.86 (1.70, 7.95)	1.33(0.46, 8.59)	501	0.033^b）
CRP (mg/L)	124.54±83.45	137.65±82.03	112.91±83.10	1.28	0.239^a）
Organ dysfunction at BSI onset
AKI [n(%)]	42(51.85)	29(65.91)	13(35.14)	7.62	0.006^c）
RRT [n(%)]	29(35.80)	20(45.45)	9(24.32)	3.90	0.048^c）
Septic shock [n(%)]	61(75.31)	41(93.18)	20(54.05)	16.55	<0.001^c）
mechancal ventilation [n(%)]	65(80.25)	38(86.36)	27(72.97)	2.27	0.132^c）
APACHE Ⅱ score at BSI onset	24(18, 28)	27(22, 29)	19(14, 26)	426.50	<0.001^b）
SOFA score at BSI onset	8(6, 11)	9(8, 13)	6(3, 8)	360.60	<0.001^b）
PBS	4(2, 5)	4(3, 6)	3(1, 4)	512.50	0.004^b）
Outcomes
Length of hospital stay（d）	55.00(31.00, 86.50)	36.00(25.25, 60.50)	80.00(11.51, 48.50)	299	<0.001^b）
Length of stay in ICU（d）	42.00(24.00, 79.00)	28.50(18.25, 51.25)	65.00(44.00, 102.50)	378.50	<0.001^b）

表1

表2

表3

表4

替加环素组与多黏菌素B组的一般资料和临床特征比较[$\bar{x} \pm s$/M(P25，P75)/n(%)]

Item	Tigecycline-based regimens (n=44)	Polymyxin B-based regimens (n=26)	t/Z/χ² value	P value
Demographic variables
Age （years）	55.73 $± 19.49$	64.15 $±$ 14.29	-2.08	0.041^a)
Male sex [n(%)]	39(88.64)	16(61.54)	7.13	0.008^c)
Body mass index (kg/m²)	25.51 $±$ 4.06	23.60 $± 5.85$	1.61	0.112^a）
NRS-2002	5(4, 6)	6(4, 6)	0.25	0.303^b)
Comorbidities
Charlson comorbidity index	2(0, 4)	3(1.75, 4.25)	0.25	0.125^b)
Diabetes mellitus [n(%)]	12(27.27)	8(30.77)	0.1.	0.754^c)
Chronic renal failure [n(%)]	4(9.09)	3(11.54)	0.00	1.0^c)
Chronic liver diseases [n(%)]	0	1(3.85)	-	0.371^c)
Biliary tract disease [n(%)]	4(9.09)	6(23.08)	1.59	0.207^c)
Congestive heart failure [n(%)]	0	2(7.69)	-	0.135^c)
COPD [n(%)]	3(6.82)	1(3.85)	0.00	1.0^c)
Malignancy [n(%)]	6(13.64)	6(23.08)	0.47	0.494^c)
Immunosuppression [n(%)]	1(2.27)	3(11.54)	1.17	0.280^c)
Health-care exposure before hospitalization [n(%)]
Antibiotic exposure (< 30 d)	28(63.64)	18(69.23)	0.23	0.634^c)
ICU admission (< 30 d)	17(38.64)	10(38.46)	0.00	0.988^c)
Surgery (< 30 d)	8(18.18)	6(23.08)	0.25	0.621^c)
Immunosuppressive therapy (< 3 months)	2(4.55)	3(11.54)	0.38	0.537^c)
Previous hospitalization (< 12 months)	29(65.12)	12(46.15)	2.63	0.105^c)
Source of infection [n(%)]
Central line	5(11.36)	2(7.69)	0.01	0.934^c)
Urinary tract	0	1(3.85)	-	0.371^c）
Intra-abdominal	28(63.63)	12(46.15)	2.04	0.153^c)
Respiratory	7(15.91)	9(34.62)	3.24	0.072^c)
Skin and soft tissue	2(4.55)	1(3.85)	0.00	1^c)
Cardio-vascular system infection	1(2.27)	0	-	1^c)
Primary	1(2.27)	1(3.85)	-	1^c)
Severity of illness at BSI onset
Biomarker at BSI onset
PCT (ng/L)	2.55(0.89, 7.95)	3.96(0.81, 14.59)	1.64	0.635^b)
CRP (mg/L)	133.39 $± 84.90$	137.78 $± 81.24$	-0.20	0.842^a)
Organ dysfunction at BSI onset
AKI [n(%)]	24(54.55)	15(57.69)	0.07	0.798^c)
RRT [n(%)]	17(38.63)	10(38.46)	0.00	0.998^c)
Septic shock [n(%)]	36(81.82)	20(76.92)	0.25	0.621^c)
Mechanical ventilation [n(%)]	39(88.64)	20(76.92)	0.92	0.336^c)
APACHE Ⅱ score	24.07 $± 7.41$	23.15 $± 8.56$	0.44	0.663^a)
SOFA score	8.00(6.00, 11.00)	8.00(5.75, 11.25)	0.02	0.864^b)
Pitt bacteremia score	4.00(3.00, 5.00)	4.00(2.75, 6.00)	0.136	0.712^b)
Outcomes
28-day mortality [n(%)]	25(56.82)	15(57.69)	0.01	0.943^c)
In-hospital mortality [n(%)]	29(65.91)	18(69.23)	0.08	0.775^c)
Length of stay（d）	63 $. 00 ± 43.02$	69.88 $± 45.57$	-0.63	0.529^a)
Length of stay before BSI（d）	23.00(12.00, 34.00)	24.50(14.50, 54.50)	0.46	0.429^b)
Length of stay in ICU（d）	41(26, 79)	51(21, 81)	0.25	0.822^b)

表4

图1

图2

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Antimicrobial regimen	Total (n=81)	Death in 28-day	P value
Tigecycline-based regimens	44	25(56.82)	0.715
Polymyxin B-based regimens	26	15(57.69)
Other regimens	11	4 (36.36)
Tigecycline-based regimens	44	25(56.82)
Tigecycline monotherapy	4	4(100)
Tigecycline + Carbapenem	27	15(55.55)
Tigecycline + Amikacin	2	0
Tigecycline + Fosfomycin	1	1(100)
Tigecycline + Sulfamethoxazole	2	1(50)
Tigecycline + Carbapenem + Amikacin	2	1(50)
Tigecycline + Carbapenem + Fosfomycin	3	2(66.67)
Tigecycline + Carbapenem + Sulfamethoxazole	2	0
Tigecycline + Carbapenem + Amikacin + Fosfomycin	1	1(100)
Polymyxin B-based regimens	26	14(53.85)
Polymyxin B monotherapy	1	0
Polymyxin B + Carbapenem	13	8(61.54)
Polymyxin B + Fosfomycin	2	0
Polymyxin B + Tigecycline	4	2(50)
Polymyxin B + Tigecycline + Carbapenem	3	2(66.67)
Polymyxin B + Carbapenem + Fosfomycin	1	1(100)
Polymyxin B + Ceftazidime-Avibactam	2	1(50)
Other regimens	11	4(36.36)
Ceftazidime-Avibactam monotherapy	1	0
Cefoperazone + Fosfomycin	2	0
Carbapenem + Fosfomycin	2	1(50)
Carbapenem + Amikacin	3	2(66.67)
Carbapenem + Sulfamethoxazole	1	0
Ceftazidime-Avibactam + Amikacin	1	1(100)
Cefoperazone-sulbactam + Fosfomycin	1	0