头孢他啶/阿维巴坦治疗重症患者耐碳青霉烯革兰阴性杆菌的临床疗效分析

doi:10.12092/j.issn.1009-2501.2026.06.015

摘要/Abstract

摘要：

目的: 探讨头孢他啶/阿维巴坦（ceftazidime-avibactam，CZA）单药与联合用药方案在治疗重症患者耐碳青霉烯类革兰阴性杆菌（carbapenem resistant organism，CRO）感染中的临床疗效，并分析影响预后的危险因素。方法: 研究纳入了2019年9月1日至2023年12月31日期间在东南大学附属中大医院住院治疗的96例CRO感染患者。根据治疗方案，将患者分为单药组（59例）和联用组（37例）。采用倾向性评分匹配（propensity score matching，PSM）方法对两组患者进行匹配，以减少基线差异。主要结局指标包括30天全因死亡率、30天临床治愈率，次要结局指标包括14天全因死亡率、微生物清除率、总住院时间、重症医学科（intensive care unit，ICU）住院时间、机械通气时间。结果: 倾向性评分匹配后共纳入74名患者，其中单药组37例，联用组37例。单药组倾向性评分匹配前30天全因死亡率为35.6%，联用组为21.6%，倾向性评分匹配后两组分别为40.5%和21.6%，匹配前后差异无统计学意义（P=0.147，P=0.079）；倾向性评分匹配前30天临床治愈率单药组和联用组分别为62.7%和73.0%，匹配后两组分别为56.8%和73.0%，匹配前后差异均无统计学意义（P=0.299，P=0.144）。然而，联用组的微生物清除率显著高于单药组（70.3% vs. 49.2%，P=0.042），倾向性评分匹配后结果仍保持稳定（P=0.010）。两组14天全因死亡率、机械通气时间、ICU住院时间以及总住院时间均无统计学差异（P>0.05）。多因素Logistic回归分析显示，使用血管活性药物、高龄是增加CRO感染患者30天全因死亡率的独立危险因素（P<0.05）；高龄、培养阳性至用药间隔久、糖尿病是降低微生物清除率的独立危险因素，而联合用药是显著提高微生物清除率的有利因素（P<0.05）。结论: 尽管联合用药方案并未在降低CRO感染患者30天全因死亡率和提高30天临床治愈率等方面体现出显著优势，但联合用药组具有更高的微生物清除率。本研究结果为CZA在CRO感染治疗中的应用提供了新的临床证据。

关键词: 头孢他啶/阿维巴坦, 耐碳青霉烯革兰阴性杆菌, 危重症患者

Abstract:

AIM: To compare the clinical efficacy of ceftazidime-avibactam (CZA) monotherapy versus combination therapy in critically ill patients with carbapenem-resistant organism (CRO) infections and to identify risk factors affecting prognosis. METHODS: A total of 96 patients with CRO infections who were hospitalized at Zhongda Hospital Southeast University from 1 September 2019 to 31 December 2023 were enrolled. Based on the treatment regimens, patients were divided into monotherapy group (n=59) and combination therapy group (n=37). Propensity score matching (PSM) was applied to balance baseline characteristics between the two groups. The primary outcomes included 30-day all-cause mortality and 30-day clinical cure rate. Secondary outcomes included 14-day all-cause mortality, microbiological clearance rate, total hospital length of stay (LOS), intensive care unit (ICU) LOS, and duration of mechanical ventilation. RESULTS: After PSM, a total of 74 patients were included, with 37 cases in each group. Before PSM, the 30-day all-cause mortality was 35.6% in the monotherapy group and 21.6% in the combination therapy group; after PSM, the rates were 40.5% and 21.6%, respectively. The differences were not statistically significant before and after matching (P=0.147, P=0.079). The 30-day clinical cure rate was 62.7% in the monotherapy group and 73.0% in the combination therapy group before PSM, 56.8% and 73.0% respectively after PSM, with no statistically significant differences before and after matching (P=0.299, P=0.144). However, the microbiological clearance rate was significantly higher in the combination therapy group compared to the monotherapy group (70.3% vs. 49.2%, P=0.042), and the result remained stable after PSM (P=0.010). There were no significant differences in 14-day all-cause mortality, total hospital LOS, ICU LOS, or duration of mechanical ventilation between the two groups (P>0.05). Multivariate logistic regression analysis showed that the use of vasopressors and advanced age were independent risk factors for increased 30-day all-cause mortality. Advanced age, longer time from the positive culture to antibiotic administration, and diabetes were independent risk factors for reduced microbiological clearance, while combination therapy was a significant favorable factor in improving microbiological clearance (P<0.05). CONCLUSION: Although the combination therapy regimen did not show a significant advantage in reducing 30-day all-cause mortality or improving 30-day clinical cure rate in patients with CRO infections, it was associated with a higher microbiological clearance rate. The findings of this study provide new clinical evidence for the application of CZA in the management of CRO infections.

Key words: ceftazidime-avibactam, carbapenem-resistant gram-negative organism, critically ill patients

中图分类号:

程紫萍, 查娴. 头孢他啶/阿维巴坦治疗重症患者耐碳青霉烯革兰阴性杆菌的临床疗效分析[J]. 中国临床药理学与治疗学, 2026, 31(6): 851-864.

Ziping CHENG, Xian ZHA. Clinical efficacy of ceftazidime/avibactam in critically ill patients with carbapenem-resistant gram-negative organism infections[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2026, 31(6): 851-864.

图/表 10

参考文献 43

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Characteristics	Before propensity score matching			After propensity score matching
Characteristics	Monotherapy group (n=59)	Combination therapy group (n=37)	P value	Monotherapy group (n=37)	Combination therapy group (n=37)	P value
Age[M(P25, P75)]	72(57,80)	67(49,75)	0.046^*	68(55,78.5)	67(49,75)	0.272
BMI (x?±s)	22.90±3.68	23.05±2.87	0.837	23.24±3.90	23.04±2.87	0.805
SOFA[M(P25, P75)]	7.0(4,10)	8.0(3.5,11)	0.587	7.3(3,11.6)	7.8(3,12.6)	0.612
APACHE Ⅱ[M(P25, P75)]	19(13,24)	17(14,23.5)	0.541	22(15,23.5)	17(14,23.5)	0.309
Male [n(%)]	43(72.9)	32(86.5)	0.117	29(78.4)	32(86.5)	0.359
Hours from admission to culture collection[M(P25, P75)]	48(8.5,96)	48(24,96)	0.477	72(24,108)	48(24,96)	0.811
Medication course[M(P25, P75)]	11 (7,14)	11(9,14.5)	0.287	11(7,14)	11(9,14.5)	0.332
Comorbidities[n(%)]
Hypertension	17(28.8)	7(18.9)	0.276	10(27)	7(18.9)	0.407
Diabetes	21(35.6)	5(13.5)	0.018^*	8(21.6)	5(13.5)	0.359
Malignancy	6(10.2)	6(16.2)	0.579	4 (10.8)	6(16.2)	0.496
Cardiovascular disease	25(42.4	15(40.5)	0.859	16(43.2)	15(40.5)	0.814
Liver disease	17(28.8)	13(35.1)	0.515	11(29.7)	13(35.1)	0.619
Kidney disease	36(61.0)	27(73.0)	0.230	27(73.0)	27(73.0)	1.000
COPD	4(6.8)	2(5.4)	1.000	4(10.8)	2(5.4)	0.670
ARDS	21(35.6)	12(32.4)	0.751	13(35.1)	12(32.4)	0.806
Severity of illness [n(%)]
CRRT	16(27.1)	12(32.4)	0.577	13(35.1)	12(32.4)	0.806
Multisite infections	24(40.7)	21(56.8)	0.124	16(43.2)	21(56.8)	0.245
Usage of vasoactive agent	35(59.3)	23(62.2)	0.782	21(56.8)	23(62.2)	0.636
Septic shock	42(71.2)	22(59.5)	0.236	24(64.9)	22(59.5)	0.632
Infection sites[n(%)]
Bloodstream	16(27.1)	19(51.4)	0.016^*	12(32.4)	19(51.4)	0.099
Urine	14(23.7)	7(18.9)	0.579	9(24.3)	7(18.9)	0.572
Abdominal	9(15.0)	7(18.9)	0.613	4(10.8)	7(18.9)	0.327
Lung	47(79.7)	28(75.7)	0.646	29(78.4)	28(75.7)	0.782
Skin	3(5.1)	1(2.7)	0.965	1(2.7)	1(2.7)	1.000
Intracranial	2(3.4)	2(5.4)	1.000	2(5.4)	2(5.4)	1.000

Characteristics	Before propensity score matching			After propensity score matching
Characteristics	Monotherapy group (n=59)	Combination therapy group (n=37)	P value	Monotherapy group (n=37)	Combination therapy group (n=37)	P value
Age[M(P25, P75)]	72(57,80)	67(49,75)	0.046^*	68(55,78.5)	67(49,75)	0.272
BMI (x?±s)	22.90±3.68	23.05±2.87	0.837	23.24±3.90	23.04±2.87	0.805
SOFA[M(P25, P75)]	7.0(4,10)	8.0(3.5,11)	0.587	7.3(3,11.6)	7.8(3,12.6)	0.612
APACHE Ⅱ[M(P25, P75)]	19(13,24)	17(14,23.5)	0.541	22(15,23.5)	17(14,23.5)	0.309
Male [n(%)]	43(72.9)	32(86.5)	0.117	29(78.4)	32(86.5)	0.359
Hours from admission to culture collection[M(P25, P75)]	48(8.5,96)	48(24,96)	0.477	72(24,108)	48(24,96)	0.811
Medication course[M(P25, P75)]	11 (7,14)	11(9,14.5)	0.287	11(7,14)	11(9,14.5)	0.332
Comorbidities[n(%)]
Hypertension	17(28.8)	7(18.9)	0.276	10(27)	7(18.9)	0.407
Diabetes	21(35.6)	5(13.5)	0.018^*	8(21.6)	5(13.5)	0.359
Malignancy	6(10.2)	6(16.2)	0.579	4 (10.8)	6(16.2)	0.496
Cardiovascular disease	25(42.4	15(40.5)	0.859	16(43.2)	15(40.5)	0.814
Liver disease	17(28.8)	13(35.1)	0.515	11(29.7)	13(35.1)	0.619
Kidney disease	36(61.0)	27(73.0)	0.230	27(73.0)	27(73.0)	1.000
COPD	4(6.8)	2(5.4)	1.000	4(10.8)	2(5.4)	0.670
ARDS	21(35.6)	12(32.4)	0.751	13(35.1)	12(32.4)	0.806
Severity of illness [n(%)]
CRRT	16(27.1)	12(32.4)	0.577	13(35.1)	12(32.4)	0.806
Multisite infections	24(40.7)	21(56.8)	0.124	16(43.2)	21(56.8)	0.245
Usage of vasoactive agent	35(59.3)	23(62.2)	0.782	21(56.8)	23(62.2)	0.636
Septic shock	42(71.2)	22(59.5)	0.236	24(64.9)	22(59.5)	0.632
Infection sites[n(%)]
Bloodstream	16(27.1)	19(51.4)	0.016^*	12(32.4)	19(51.4)	0.099
Urine	14(23.7)	7(18.9)	0.579	9(24.3)	7(18.9)	0.572
Abdominal	9(15.0)	7(18.9)	0.613	4(10.8)	7(18.9)	0.327
Lung	47(79.7)	28(75.7)	0.646	29(78.4)	28(75.7)	0.782
Skin	3(5.1)	1(2.7)	0.965	1(2.7)	1(2.7)	1.000
Intracranial	2(3.4)	2(5.4)	1.000	2(5.4)	2(5.4)	1.000

Clinical outcome	Before propensity score matching			After propensity score matching
Clinical outcome	Monotherapy group (n=59)	Combination therapy group (n=37)	P value	Monotherapy group (n=37)	Combination therapy group (n=37)	P value
Primary outcomes
30-day all-cause mortality [n(%)]	21(35.6)	8(21.6)	0.147	15(40.5)	8(21.6)	0.079
30-day clinical response [n(%)]	37(62.7)	27(73.0)	0.299	21(56.8)	27(73.0)	0.144
Secondary outcomes
14-day all-cause mortality [n(%)]	17(28.8)	8(21.6)	0.435	12(32.4)	8(21.6)	0.295
Microbiological clearance[n(%)]	29(49.2)	26(70.3)	0.042^*	15(40.5)	26(70.3)	0.010^*
Duration of mechanical ventilation (days) [M(P25, P75)]	13(6,29)	19(9.5,30)	0.381	15(6.5,32)	19(9.5,30)	0.618
Length of ICU stay (days) [M(P25, P75)]	22 (12,37)	25(18,52.5)	0.119	22 (12,35)	25(18,52.5)	0.211
Length of hospital stay (days) [M(P25, P75)]	32(20,54)	46(27.5,76.5)	0.031^*	32(21.5,52.5)	46(27.5,76.5)	0.057

Clinical outcome	Before propensity score matching			After propensity score matching
Clinical outcome	Monotherapy group (n=59)	Combination therapy group (n=37)	P value	Monotherapy group (n=37)	Combination therapy group (n=37)	P value
Primary outcomes
30-day all-cause mortality [n(%)]	21(35.6)	8(21.6)	0.147	15(40.5)	8(21.6)	0.079
30-day clinical response [n(%)]	37(62.7)	27(73.0)	0.299	21(56.8)	27(73.0)	0.144
Secondary outcomes
14-day all-cause mortality [n(%)]	17(28.8)	8(21.6)	0.435	12(32.4)	8(21.6)	0.295
Microbiological clearance[n(%)]	29(49.2)	26(70.3)	0.042^*	15(40.5)	26(70.3)	0.010^*
Duration of mechanical ventilation (days) [M(P25, P75)]	13(6,29)	19(9.5,30)	0.381	15(6.5,32)	19(9.5,30)	0.618
Length of ICU stay (days) [M(P25, P75)]	22 (12,37)	25(18,52.5)	0.119	22 (12,35)	25(18,52.5)	0.211
Length of hospital stay (days) [M(P25, P75)]	32(20,54)	46(27.5,76.5)	0.031^*	32(21.5,52.5)	46(27.5,76.5)	0.057

Pathogen	Infection source	n	Proportion
Klebsiella pneumoniae		91	81.25%
	Lung	36	32.14%
	Abdominal	9	8.04%
	Urine	14	12.50%
	Skin	2	1.79%
	Bloodstream	27	24.11%
	Intracranial	3	2.68%
Pseudomonas aeruginosa		17	15.18%
	Lung	15	13.39%
	Abdominal	1	0.89%
	Urine	1	0.89%
Escherichia coli	Urine	1	0.89%
Hoffmann's enterobacterium	Intracranial	1	0.89%
Enterobacter cloacae	Abdominal	1	0.89%
Serratia marcescens	Bloodstream	1	0.89%