Ceftazidime-Avibactam versus polymyxin B in the treatment of pneumonia caused by carbapenem-resistant Klebsiella pneumoniae pneumonia

doi:10.3877/cma.j.issn.2096-1537.2024.01.003

Abstract

Abstract:

Objective

To assess the efficacy and safety of Ceftazidime-Avibactam (CAZ-AVI) versus polymyxin B-based anti-infective therapy in patients with severe carbapenem-resistant Klebsiella pneumoniae (CRKP) pneumonia.

Methods

From June 2019 to September 2020, the data from patients in ICU of the First Affiliated Hospital of Nanjing Medical University were retrospectively analyzed. These patients were diagnosed with pneumonia caused by CRKP and were treated with either CAZ-AVI or polymyxin B-based anti-infective therapy. Clinical and microbiologic cure rates, 28-day survival, and safety evaluation were compared between patients in two groups.

Results

Among the 86 subjects, CRKP clearance was 71.7% (33/46) in the CAZ-AVI group and 45.0% (18/40) in the polymyxin B group, there was significant difference between two groups (χ²=6.338, P=0.012). The clinical cure rate was 52.2% (24/46), the 28-day survival rate was 69.6% (32/46) in the CAZ-AVI group while 32.5% (13/40) and 75.0% (30/40) in polymyxin B group, there were no significant difference between two groups (χ²=3.378, P=0.066; χ²=0.314, P=0.575). The multivariate logistic regression analysis and propensity score (PS) regression adjustment method were employed. The results indicated that the clinical cure rate was significantly higher in the CAZ-AVI group compared to the polymyxin B group (P values of 0.017 and 0.025, respectively). The adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were 3.550 (1.250-10.078) and 3.062 (1.150-8.149), respectively. The microbial clearance in CAZ-AVI patients was significantly higher relative to the polymyxin B group (P values: 0.012, 0.015, respectively), adjusted ORs and 95% CIs were 3.320 (1.308-8.427), 3.297 (1.259-8.637). There was no significant difference in 28-day survival between the 2 groups (P values were 0.990 and 0.850, respectively). The CAZ-AVI group had a lower incidence of adverse reactions when compared with the polymyxin B group (8.7% vs 30.0%, χ²=6.413, P =0.011).

Conclusion

CAZ-AVI be a reasonable alternative to polymyxin B in the treatment of pneumonia caused by CRKP.

Key words: Carbapenem-resistant Klebsiella pneumoniae, Polymyxin B, Ceftazidime-Avibactam, Clinical outcomes, Safety evaluation

Ying Shi, Jing Hu, Peiben Liu, Tingting Wang, Xiangrong Zuo, Quan Cao. Ceftazidime-Avibactam versus polymyxin B in the treatment of pneumonia caused by carbapenem-resistant Klebsiella pneumoniae pneumonia[J]. Chinese Journal of Critical Care & Intensive Care Medicine(Electronic Edition), 2024, 10(01): 16-24.

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References 45

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基线资料及临床结局	CAZ-AVI组（46例）	多黏菌素B组（40例）	统计值	P值
男性[例（%）]	41（89.1）	27（67.5）	χ²=6.049	0.014
年龄（岁，）	59.7±18.6	59.9±16.0	t=0.043	0.966
基础疾病[例（%）]
心血管疾病	30（65.2）	25（62.5）	χ²=0.069	0.793
脑血管疾病	14（30.4）	8（20.0）	χ²=1.224	0.269
慢性呼吸系统疾病	1（2.2）	1（2.5）	-	1.000
糖尿病	15（32.6）	8（20.0）	χ²=1.736	0.188
肿瘤	6（13.0）	2（5.0）	-	0.275
慢性肝病	2（4.3）	1（2.5）	-	1.000
慢性肾病	4（8.7）	2（5.0）	-	0.681
Charlson指数[M（Q₂₅，Q₇₅）]	2.00（0，4.00）	1.00（0.25，3.00）	Z=0.873	0.383
CRRT[例（%）]	20（43.5）	15（37.5）	χ²=0.317	0.574
VAP[例（%）]	34（73.9）	27（67.5）	χ²=0.427	0.514
感染时SOFA评分（分，）	7.0±3.8	6.4±2.8	t=0.951	0.344
感染时APACHEⅡ评分（分，）	14.3±5.8	13.4±3.7	t=0.945	0.348
合并的多部位感染[例（%）]
合并血流感染	6（13.0）	8（20.0）	χ²=0.760	0.383
合并尿路感染	9（19.6）	4（10.0）	χ²=1.526	0.217
合并皮肤软组织感染	4（8.7）	3（7.5）	-	1.000
合并腹腔感染	3（6.5）	4（10.0）	-	0.700
联合使用抗生素种类[例（%）]
联合碳青霉烯类	20（43.5）	20（50.0）	χ²=0.366	0.545
联合阿米卡星	11（23.9）	8（20.0）	χ²=0.190	0.663
联合氨曲南	2（4.3）	0	-	0.497
联合磷霉素	2（4.3）	2（5.0）	-	1.000
联合替加环素	6（13.0）	10（25.0）	χ²=2.020	0.155
单药治疗	9（19.6）	5（12.5）	χ²=0.784	0.376
临床结局[例（%）]
临床治愈	24（52.2）	13（32.5）	χ²=3.378	0.066
细菌清除	33（71.7）	18（45.0）	χ²=6.338	0.012
28 d生存	32（69.6）	30（75.0）	χ²=0.314	0.575

基线资料及临床结局	CAZ-AVI组（46例）	多黏菌素B组（40例）	统计值	P值
男性[例（%）]	41（89.1）	27（67.5）	χ²=6.049	0.014
年龄（岁，）	59.7±18.6	59.9±16.0	t=0.043	0.966
基础疾病[例（%）]
心血管疾病	30（65.2）	25（62.5）	χ²=0.069	0.793
脑血管疾病	14（30.4）	8（20.0）	χ²=1.224	0.269
慢性呼吸系统疾病	1（2.2）	1（2.5）	-	1.000
糖尿病	15（32.6）	8（20.0）	χ²=1.736	0.188
肿瘤	6（13.0）	2（5.0）	-	0.275
慢性肝病	2（4.3）	1（2.5）	-	1.000
慢性肾病	4（8.7）	2（5.0）	-	0.681
Charlson指数[M（Q₂₅，Q₇₅）]	2.00（0，4.00）	1.00（0.25，3.00）	Z=0.873	0.383
CRRT[例（%）]	20（43.5）	15（37.5）	χ²=0.317	0.574
VAP[例（%）]	34（73.9）	27（67.5）	χ²=0.427	0.514
感染时SOFA评分（分，）	7.0±3.8	6.4±2.8	t=0.951	0.344
感染时APACHEⅡ评分（分，）	14.3±5.8	13.4±3.7	t=0.945	0.348
合并的多部位感染[例（%）]
合并血流感染	6（13.0）	8（20.0）	χ²=0.760	0.383
合并尿路感染	9（19.6）	4（10.0）	χ²=1.526	0.217
合并皮肤软组织感染	4（8.7）	3（7.5）	-	1.000
合并腹腔感染	3（6.5）	4（10.0）	-	0.700
联合使用抗生素种类[例（%）]
联合碳青霉烯类	20（43.5）	20（50.0）	χ²=0.366	0.545
联合阿米卡星	11（23.9）	8（20.0）	χ²=0.190	0.663
联合氨曲南	2（4.3）	0	-	0.497
联合磷霉素	2（4.3）	2（5.0）	-	1.000
联合替加环素	6（13.0）	10（25.0）	χ²=2.020	0.155
单药治疗	9（19.6）	5（12.5）	χ²=0.784	0.376
临床结局[例（%）]
临床治愈	24（52.2）	13（32.5）	χ²=3.378	0.066
细菌清除	33（71.7）	18（45.0）	χ²=6.338	0.012
28 d生存	32（69.6）	30（75.0）	χ²=0.314	0.575

因素	粗OR值（95%CI）	P值	校正OR值^a（95%CI）	P值	B	SE	Wald
临床治愈^b
CAZ-AVI治疗	2.266（0.941~5.456）	0.068	3.550（1.25~10.078）	0.017	1.267	0.532	5.663
肿瘤史	0.167（0.02~1.419）	0.101	0.126（0.014~1.158）	0.067	-2.017	1.131	3.351
CRRT	0.284（0.111~0.726）	0.009	0.378（0.123~1.158）	0.088	-0.973	0.571	2.902
感染时SOFA评分	0.760（0.645~0.896）	0.001	0.801（0.664~0.966）	0.020	-0.222	0.095	5.404
合并腹腔感染	0.199（0.023~1.731）	0.144	0.280（0.025~3.177）	0.305	-1.271	1.238	1.054
细菌清除^c
CAZ-AVI治疗	3.103（1.269~7.588）	0.013	3.320（1.308~8.427）	0.012	1.200	0.475	6.379
感染时SOFA评分	0.927（0.814~1.055）	0.248	0.923（0.801~1.065）	0.272	-0.080	0.073	1.209
合并腹腔感染	0.245（0.045~1.343）	0.105	0.328（0.054~2.000）	0.227	-1.115	0.922	1.461
28 d生存^d
CAZ-AVI治疗	0.762（0.294~1.974）	0.576	0.992（0.260~3.777）	0.990	-0.008	0.682	0.000
年龄	0.950（0.917~0.985）	0.006	0.925（0.871~0.982）	0.011	-0.078	0.031	6.459
心脏疾病	0.173（0.047~0.642）	0.009	0.189（0.028~1.265）	0.086	-1.663	0.969	2.949
Charlson指数	0.834（0.683~1.019）	0.076	1.090（0.789~1.505）	0.602	0.086	0.165	0.271
CRRT	0.366（0.139~0.962）	0.042	1.023（0.205~5.115）	0.978	0.023	0.821	0.001
VAP	0.390（0.118~1.291）	0.123	1.077（0.201~5.765）	0.931	0.074	0.856	0.007
感染时SOFA评分	0.670（0.551~0.814）	<0.001	0.545（0.395~0.754）	<0.001	-0.607	0.165	13.500
感染时APACHE评分	0.870（0.784~0.965）	0.009

因素	粗OR值（95%CI）	P值	校正OR值^a（95%CI）	P值	B	SE	Wald
临床治愈^b
CAZ-AVI治疗	2.266（0.941~5.456）	0.068	3.550（1.25~10.078）	0.017	1.267	0.532	5.663
肿瘤史	0.167（0.02~1.419）	0.101	0.126（0.014~1.158）	0.067	-2.017	1.131	3.351
CRRT	0.284（0.111~0.726）	0.009	0.378（0.123~1.158）	0.088	-0.973	0.571	2.902
感染时SOFA评分	0.760（0.645~0.896）	0.001	0.801（0.664~0.966）	0.020	-0.222	0.095	5.404
合并腹腔感染	0.199（0.023~1.731）	0.144	0.280（0.025~3.177）	0.305	-1.271	1.238	1.054
细菌清除^c
CAZ-AVI治疗	3.103（1.269~7.588）	0.013	3.320（1.308~8.427）	0.012	1.200	0.475	6.379
感染时SOFA评分	0.927（0.814~1.055）	0.248	0.923（0.801~1.065）	0.272	-0.080	0.073	1.209
合并腹腔感染	0.245（0.045~1.343）	0.105	0.328（0.054~2.000）	0.227	-1.115	0.922	1.461
28 d生存^d
CAZ-AVI治疗	0.762（0.294~1.974）	0.576	0.992（0.260~3.777）	0.990	-0.008	0.682	0.000
年龄	0.950（0.917~0.985）	0.006	0.925（0.871~0.982）	0.011	-0.078	0.031	6.459
心脏疾病	0.173（0.047~0.642）	0.009	0.189（0.028~1.265）	0.086	-1.663	0.969	2.949
Charlson指数	0.834（0.683~1.019）	0.076	1.090（0.789~1.505）	0.602	0.086	0.165	0.271
CRRT	0.366（0.139~0.962）	0.042	1.023（0.205~5.115）	0.978	0.023	0.821	0.001
VAP	0.390（0.118~1.291）	0.123	1.077（0.201~5.765）	0.931	0.074	0.856	0.007
感染时SOFA评分	0.670（0.551~0.814）	<0.001	0.545（0.395~0.754）	<0.001	-0.607	0.165	13.500
感染时APACHE评分	0.870（0.784~0.965）	0.009

分析方法	临床治愈		细菌清除		28 d生存
分析方法	OR（95% CI）	P值	OR（95% CI）	P值	OR（95% CI）	P值
单因素分析	2.266（0.941~5.456）	0.068	3.103（1.269~7.588）	0.013	0.762（0.294~1.974）	0.576
多因素分析	3.550（1.250~10.078）	0.017	3.320（1.308~8.427）	0.012	0.992（0.260~3.777）	0.990
PS回归调整	3.062（1.150~8.149）	0.025	3.297（1.259~8.637）	0.015	0.906（0.326~2.517）	0.850

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