1.Pharmaceutical Care for One Case of Uremia Complicated with Pulmonary Infection and Epilepsy
Xia WANG ; Yirui WANG ; Ni YAN ; Zhongming Lü
China Pharmacist 2016;19(10):1922-1924
Objective:To explore the pharmaceutical care on an uremia patient with pulmonary infection complicated with epilepsy to provide ideas for clinical pharmacists in the clinical practice. Methods: According diagnosis and drug treatment characteristic of Chronic renal insufficiency, clinical pharmacist supplied individual treatment regiment and treatment of complications and adverse drug reactions occurred in the course of treatment, and pharmaceutical care for the patient in the whole process. Results: Pharmaceutical care on patients with uremia complicated with pulmonary should focous on the safety and rationality of the used of antibiotics, the poten-tial interaction of drugs, the treatment of adverse drug reaction, and the education of patients. Conclusion:Clinical pharmacist should supplied conventional pharmaceutical care on patients with uremia complicated with pulmonary to improve the safety and effectiveness of drug treatment.
2.Long term clinical outcomes in patients with moderate renal insufficiency undergoing stent based percutaneous coronary intervention.
Rui-yan ZHANG ; Jing-wei NI ; Jian-sheng ZHANG ; Jian HU ; Zhen-kun YANG ; Qi ZHANG ; An-kang LÜ ; Wei-feng SHEN
Chinese Medical Journal 2006;119(14):1176-1181
BACKGROUNDPatients with end-stage renal disease have a high mortality from coronary artery disease, but the impact of moderate renal insufficiency on clinical outcomes after percutaneous coronary intervention (PCI) and the effect of drug-eluting stent implantation in these patients remain unclear. This study determined the long-term effect of moderate renal insufficiency on death and major adverse cardiac events (MACE) after stent based PCI and examined whether drug-eluting stent implantation could favourably influence clinical outcome.
METHODSMajor adverse cardiac events and causes of mortality were determined for 1012 patients undergoing percutaneous intervention from January 1, 2002 to December 31, 2004 at Shanghai Ruijin Hospital. Based on estimated creatinine clearance levels, long term outcomes were compared between patients with estimated creatinine clearance < 60 ml/min (renal insufficiency group; n = 410) and those with estimated creatinine clearance > or = 60 ml/min (control group; n = 602). Subgroup analysis was also made for patients with renal insufficiency between drug eluting stent (n = 264) and bare metal stent implantation (n = 146) during PCI.
RESULTSDuring follow-up (average 17 months) after successful PCI, all causes of death (7.1% vs 2.3%, P < 0.01) and cardiac death (3.4% vs 1.0%, all P < 0.01) were significantly higher in renal insufficiency group than in control group. For patients with moderate renal insufficiency, drug-eluting stent implantation reduced significantly all causes of death (5.3% vs 10.9%, P < 0.05) and occurrence of major cardiac adverse events (15.1% vs 24.6%, P < 0.05) compared with bare metal stents.
CONCLUSIONSModerate renal insufficiency is an important clinical factor influencing the mortality after PCI in patients with coronary artery disease and the use of drug-eluting stents should be the preferred therapy for the improvement of long-term outcomes in such patients.
Aged ; Angioplasty, Balloon, Coronary ; Coronary Angiography ; Drug Delivery Systems ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Renal Insufficiency ; mortality ; Stents
3.OATP1B1 in drug-drug interactions between traditional Chinese medicine Danshensu and rosuvastatin.
Jin-hua WEN ; Xiao-hua WEI ; Xiao-hua CHENG ; Rong ZUO ; Hong-wei PENG ; Yan-ni LÜ ; Jian ZHOU ; Xue-lian ZHENG ; Jun CAI ; Yu-qing XIONG ; Li CAO
Acta Pharmaceutica Sinica 2016;51(1):75-79
The study was designed to explore the drug-drug interactions mechanisms mediated by OATP1B1 between traditional Chinese medicine Danshensu and rosuvastatin. First, the changes of rosuvastatin pharmacokinetics were investigated in presence of Danshensu in rats. Then, the primary rat hepatocytes model was established to explore the effects of Danshensu on the uptake of rosuvastatin by hepatocytes. Finally, HEK293T cells with overexpression of OATP1B1*a and OATP1B1*5 were established using a lentiviral delivery system to explore the effects of Danshensu on the uptake of rosuvastatin. Rosuvastatin pharmacokinetic parameters of C(max0, AUCO(0-t), AUC(0-∞) were increased about 123%, 194% and 195%, by Danshensu in rats, while the CL z/F value was decreased by 60%. Uptake of rosuvastatin in the primary rat hepatocytes was decreased by 3.13%, 41.15% and 74.62%, respectively in the presence of 20, 40 and 80 μmol x L(-1) Danshensu. The IC50 parameters was (53.04 ± 2.43) μmol x L(-1). The inhibitory effect of Danshensu on OATP1B1 mediated transport of rosuvastatin was related to the OATP1B1 gene type. In OATP1B1*5-HEK293T mutant cells, transport of rosuvastatin were reduced by (39.11 ± 4.94)% and (63.61 ± 3.94)%, respectively, by Danshensu at 1 and 10 μmol x L(-1). While transport of rosuvastatin was reduced by (8.22 ± 2.40)% and (11.56 ± 3.04)% and in OATP1B1*1a cells, respectively. Danshensu significantly altered the pharmacokinetics of rosuvastatin in rats, which was related to competitive inhibition of transport by OATPJBI. Danshensu exhibited a significant activity in the inhibition of rosuvastatin transport by OATP1B1*5-HEK293T, but not by OATP1B1*1a, suggesting a dependence on OATP1B1 sequence.
Animals
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Drug Interactions
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Drugs, Chinese Herbal
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pharmacology
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HEK293 Cells
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Hepatocytes
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drug effects
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metabolism
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Humans
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Lactates
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pharmacology
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Organic Anion Transporters
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metabolism
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Rats
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Rosuvastatin Calcium
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pharmacology
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Solute Carrier Organic Anion Transporter Family Member 1b1
4.Endoscopic endonasal surgery for clival tumor.
Qiu-hang ZHANG ; Feng KONG ; Bo YAN ; Zhi-li NI ; Hai-li LÜ
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2007;42(1):7-10
OBJECTIVETo review our experience with endoscopic endonasal approach for surgical management of clival tumors.
METHODSTwenty-four patients with clival tumors treated by endoscopic endonasal surgery between August 2002 and November 2005 were studied prospectively. The operative technique was described in detail. There were 5 chordoma, 2 ossifying fibroma, 1 meningioma, 1 craniopharyngioma, 1 hemangioblastoma, 6 squamous cancer, 2 chondrosarcoma, 2 chondrosarcoma, 1 lymphoma, 1 malignant giant cell tumor and 2 metastatic carcinoma.
RESULTSTotal tumor removal was obtained in 22 cases, subtotal removal in 2 case. Follow-up ranged 12 to 51 months. Three patients dead. Five patients with total removal recurred, one of them dead. Two patients with subtotal removal dead, one with chondrosarcoma and one with chordoma. The complications included subarachnoid hemorrhage in 1 patient, and transient cerebrospinal leakage in 2 cases.
CONCLUSIONSThe use of nasoendoscopy to perform clival tumor surgery is not only limited to the minimally invasive aspect, it also provides better visualization of deeper structures in the skull base, provides the ability to 'look around corners' and wide exposed field. This approach permits us to manage clival lesions properly.
Adolescent ; Adult ; Aged ; Cranial Fossa, Posterior ; surgery ; Endoscopy ; methods ; Female ; Humans ; Male ; Middle Aged ; Nose ; surgery ; Prospective Studies ; Skull Base Neoplasms ; surgery ; Treatment Outcome ; Young Adult
5.Blood lead levels among children aged 0 to 6 years in 16 cities of China, 2004-2008.
Xiao-Hua XIE ; Zang-Wen TAN ; Ni JIA ; Zhao-Yang FAN ; Shuai-Ming ZHANG ; Yan-Yu LÜ ; Li CHEN ; Yao-Hua DAI
Chinese Medical Journal 2013;126(12):2291-2295
BACKGROUNDThe adverse health effects of lead for children under 6 years are well known. Studies to assess the lead exposure among children in China are small in sample size and lack of national representative data. The aim of this study therefore was to describe blood lead levels and identify risk factors for lead exposure among children aged 0 to 6 years living in 16 cities in China.
METHODSWe analyzed data from blood lead levels surveillance in China carried out in 16 large cities between 2004 and 2008. A stratified clustered random sampling strategy was used. A total of 69 968 children aged 0 to 6 years were included. We conducted multiple Logistic regression analyses to explore risk factors to high blood lead level.
RESULTSThe geometric mean blood lead level of the children was 4.50 µg/dl (median: 4.90 µg/dl; IQR: 3.20 - 7.00 µg/dl). Overall prevalence of blood lead level ≥ 10.00 µg/dl among 0- to 6-year-old children was 7.57%. But the proportion of blood lead level ≥ 5.00 but < 10.00 µg/dl was 42.12%. Blood lead levels were significantly higher in boys (4.63 µg/dl) than in girls (4.35 µg/dl) (P < 0.0001). The geometric mean blood lead levels and prevalence of blood lead level ≥ 10.00 µg/dl increased with age (P < 0.0001 for the two trends). After controlling for sociodemographic, dietary and behavior factors, multivariable analysis indicated that lower maternal education, male gender, younger age, often biting pencil or/and toys, walking or playing for long time on the street, not washing hands before eating are major risk factors for higher lead levels.
CONCLUSIONSThe blood lead levels among Chinese children in urban areas are lower than previous studies but close to those of developed countries. However, children with low lead exposure account for almost half and the sociodemographic factors (age, male sex, and low mother education level) continue to be associated with higher blood lead levels.
Child, Preschool ; China ; Female ; Humans ; Infant ; Infant, Newborn ; Lead ; blood ; Logistic Models ; Male ; Time Factors ; Urban Health
6.Diagnostic value of transbronchial needle aspiration combined with transesophageal endoscopic ultrasound-guided fine needle aspiration in mediastinal and pulmonary hilar lesions.
Xiao-Yan LI ; Gui-Yu CHENG ; Zhi-Hui ZHANG ; Ning LÜ ; Yue-Ming ZHANG ; Shuang-Mei ZOU ; Li-Yan XUE ; Lei ZHANG ; Xiao-Guang NI ; Shao-Qing LAI ; Shun HE ; Gui-Xiang YU ; Feng-Huan JU ; Hua-Ying XUN ; Rong-Rong CHENG ; Gui-Qi WANG
Chinese Journal of Oncology 2009;31(7):536-540
OBJECTIVETo evaluate the value of transbronchial needle aspiration (TBNA) combined with transesophageal endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) in the diagnosis of mediastinal and pulmonary hilar lesions as well as in the lymph node staging (N staging) of lung cancer.
METHODS129 patients with mediastinal and pulmonary hilar lesions underwent either TBNA or EUS-FNA with cytological needle aspiration. The samples obtained from TBNA or EUS-FNA were examined by both cytologiy and histopathology.
RESULTSOf the 129 patients, 59 underwent TBNA and 70 EUS-FNA. The diagnostic rate were 84.7% (50/59) by TBNA and 94.3% (66/70) by EUS-FNA, resepectively. The diagnosis of 116 (89.9%) patients were confirmed by either TBNA or EUS-FNA. The pathological and cytological diagnostic rates were 92.2% (107/116) and 88.0% (102/116), resepectively. The diagnostic rate was elevated by 8.4% (9/107) through pathological examination. The histological classification rates by cytological and pathological examination were 73.8% (76/116) and 89.3% (92/103), respectively. The diagnostic rate of histological classification was elevated by 35.5% (27/76) through pathological examination.
CONCLUSIONThe combination of TBNA and EUS-FNA can improve the diagnostic rate for wider mediastinal and pulmlonary hilar lesions. Pathological examination of the samples obtained from the TBNA and EUS-FNA can elevate not only the rate of diagnosis but also the rate of histological classification.
Adenocarcinoma ; diagnostic imaging ; pathology ; Adolescent ; Adult ; Aged ; Aged, 80 and over ; Biopsy, Fine-Needle ; methods ; Biopsy, Needle ; Carcinoma, Squamous Cell ; diagnostic imaging ; pathology ; Endosonography ; methods ; Female ; Humans ; Lung Neoplasms ; diagnostic imaging ; pathology ; Lymph Nodes ; diagnostic imaging ; pathology ; Lymphatic Metastasis ; Male ; Mediastinal Neoplasms ; diagnostic imaging ; pathology ; secondary ; Mediastinum ; Middle Aged ; Neoplasm Staging ; Small Cell Lung Carcinoma ; diagnostic imaging ; pathology ; Young Adult
7.Asymptomatic patients of chronic obstructive pulmonary disease in China.
Ming LU ; Wan-zhen YAO ; Nan-shan ZHONG ; Yu-min ZHOU ; Chen WANG ; Ping CHEN ; Jian KANG ; Shao-guang HUANG ; Bao-yuan CHEN ; Chang-zheng WANG ; Dian-tao NI ; Xiao-ping WANG ; Da-li WANG ; Sheng-ming LIU ; Jia-chun LÜ ; Ning SHEN ; Yan-ling DING ; Pi-xin RAN
Chinese Medical Journal 2010;123(12):1494-1499
BACKGROUNDChronic obstructive pulmonary disease (COPD) has a variable natural history and not all individuals follow the same course. This study aimed to identify the prevalence and characteristics of asymptomatic COPD patients from a population-based survey in China.
METHODSA multistage cluster sampling strategy was used in a population from seven different provinces/cities. All residents (over 40 years old) were interviewed with a standardized questionnaire and spirometry. Post-bronchodilator forced expiratory volume in 1 second (FEV(1))/forced vital capacity (FVC) of less than 70% was defined as the diagnostic criterion of COPD. All COPD patients screened were divided into symptomatic group and asymptomatic group according to the presence or absence of chronic respiratory symptoms. Socio-demographic, personal and exposure variables were collected and analyzed.
RESULTSAmong the 1668 patients who were diagnosed with COPD from the 25 627 sampling subjects, 589 (35.3%) were asymptomatic. The age, sex, body mass index (BMI), rural and urban distributions, smoking habit and education levels were similar in the two groups. A total of 64.7% of the asymptomatic patients had no comorbidities. Cardiovascular diseases and lung cancer were more common among symptomatic COPD patients than asymptomatic group. Asymptomatic COPD group were less likely to present with poor ventilation in the kitchen, a family history of respiratory disease and recurrent childhood cough. Asymptomatic COPD patients had significantly higher FEV(1) (73.1% vs. 61.0%), FVC (91.9% vs. 82.0%), and a higher ratio of FEV(1)/FVC (62.9% vs. 58.7%) (all P < 0.001) than symptomatic group. More asymptomatic patients were underdiagnosed (91.9% vs. 54.3%, P < 0.001) than symptomatic patients.
CONCLUSIONSThis large population-based survey confirmed a high prevalence of asymptomatic COPD patients in China. More use of spirometry screening test may be important to the early detection of COPD.
Adult ; Aged ; Aged, 80 and over ; China ; epidemiology ; Educational Status ; Female ; Humans ; Male ; Middle Aged ; Pulmonary Disease, Chronic Obstructive ; diagnosis ; epidemiology ; Risk Factors ; Smoking ; Spirometry ; Surveys and Questionnaires
8.Detection of Carbamazepine and Its Metabolites in Blood Samples by LC-MS/MS.
Hai-Yan CUI ; Chen-Xi LÜ ; Yan-Hua SHI ; Ni YUAN ; Jia-Hao LIANG ; Quan AN ; Zhong-Yuan GUO ; Ke-Ming YUN
Journal of Forensic Medicine 2023;39(1):34-39
OBJECTIVES:
To establish a method for the detection of carbamazepine and its metabolites 10,11-dihydro-10,11-epoxycarbamazepine and 10,11-dihydro-10-hydroxycarbamazepine in blood samples by liquid chromatography-tandem mass spectrometry (LC-MS/MS).
METHODS:
The blood samples were treated with 1-butyl-3-methylimidazolium hexafluorophosphate as an extraction solvent. The samples were extracted by ultrasound-assisted extraction and separated by ZORBAX Eclipse Plus C18, 95Å column. The mobile phase A aqueous solution containing 0.1% formic acid and 10 mmol/L ammonium acetate, and mobile phase B mixed organic solvent containing acetonitrile/methanol (Vacetonitrile∶Vmethanol=2∶3) were used for gradient elution at the flow rate of 1.00 mL/min. An electrospray ion source in positive mode was used for detection in the multiple reaction monitoring.
RESULTS:
The linearities of carbamazepine and its metabolites 10,11-dihydro-10,11-epoxycarbamazepine and 10,11-dihydro-10-hydroxycarbamazepine in blood samples were good within the corresponding range, with correlation coefficients (r) greater than 0.995 6. The limits of detection were 3.00, 0.40 and 1.30 ng/mL, respectively. The limit of quantitation were 8.00, 1.00 and 5.00 ng/mL, respectively. The extraction recoveries ranged from 76.00% to 106.44%. The relative standard deviations of the intra-day and inter-day precisions were less than 16%. Carbamazepine and its main metabolite 10,11-dihydro-10,11-epoxycarbamazepine were detected in blood samples of death cases with a mass concentration of 2.71 μg/mL and 252.14 ng/mL, respectively.
CONCLUSIONS
This method has high sensitivity and good selectivity, which is suitable for the detection of carbamazepine and its metabolites in blood samples, and can be used for carbamazepine-related forensic identifications.
Chromatography, Liquid/methods*
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Tandem Mass Spectrometry
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Methanol
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Carbamazepine/analysis*
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Benzodiazepines/analysis*
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Solvents
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Chromatography, High Pressure Liquid
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Solid Phase Extraction
9.OATP1B1 in drug-drug interactions between traditional Chinese medicine Danshensu and rosuvastatin
Jin-hua WEN ; Xiao-hua WEI ; Xiao-hua CHENG ; Rong ZUO ; Hong-wei PENG ; Yan-ni LÜ ; Jian ZHOU ; Xue-lian ZHENG ; Jun CAI ; Yu-qing XIONG ; Li CAO
Acta Pharmaceutica Sinica 2016;51(1):75-
The study was designed to explore the drug-drug interactions mechanisms mediated by OATP1B1 between traditional Chinese medicine Danshensu and rosuvastatin. First, the changes of rosuvastatin pharmacokinetics were investigated in presence of Danshensu in rats. Then, the primary rat hepatocytes model was established to explore the effects of Danshensu on the uptake of rosuvastatin by hepatocytes. Finally, HEK293T cells with overexpression of OATP1B1*1a and OATP1B1*5 were established using a lentiviral delivery system to explore the effects of Danshensu on the uptake of rosuvastatin. Rosuvastatin pharmacokinetic parameters of Cmax, AUC0-t, AUC0-∞ were increased about 123%, 194% and 195%, by Danshensu in rats, while the CLz/F value was decreased by 60%. Uptake of rosuvastatin in the primary rat hepatocytes was decreased by 3.13%, 41.15% and 74.62%, respectively in the presence of 20, 40 and 80 μmol·L-1 Danshensu. The IC50 parameters was (53.04 ± 2.43) μmol·L-1. The inhibitory effect of Danshensu on OATP1B1 mediated transport of rosuvastatin was related to the OATP1B1 gene type. In OATP1B1*5-HEK293T mutant cells, transport of rosuvastatin were reduced by (39.11 ± 4.94) % and (63.61 ± 3.94) %, respectively, by Danshensu at 1 and 10 μmol·L-1. While transport of rosuvastatin was reduced by (8.22 ± 2.40) % and (11.56 ± 3.04) % and in OATP1B1*1a cells, respectively. Danshensu significantly altered the pharmacokinetics of rosuvastatin in rats, which was related to competitive inhibition of transport by OATP1B1. Danshensu exhibited a significant activity in the inhibition of rosuvastatin transport by OATP1B1*5-HEK293T, but not by OATP1B1*1a, suggesting a dependence on OATP1B1 sequence.
10.Changing resistance profiles of Enterobacter isolates in hospitals across China:results from the CHINET Antimicrobial Resistance Surveillance Program,2015-2021
Shaozhen YAN ; Ziyong SUN ; Zhongju CHEN ; Yang YANG ; Fupin HU ; Demei ZHU ; Yi XIE ; Mei KANG ; Fengbo ZHANG ; Ping JI ; Zhidong HU ; Jin LI ; Sufang GUO ; Han SHEN ; Wanqing ZHOU ; Yingchun XU ; Xiaojiang ZHANG ; Xuesong XU ; Chao YAN ; Chuanqing WANG ; Pan FU ; Wei JIA ; Gang LI ; Yuanhong XU ; Ying HUANG ; Dawen GUO ; Jinying ZHAO ; Wen'en LIU ; Yanming LI ; Hua YU ; Xiangning HUANG ; Bin SHAN ; Yan DU ; Shanmei WANG ; Yafei CHU ; Yuxing NI ; Jingyong SUN ; Yunsong YU ; Jie LIN ; Chao ZHUO ; Danhong SU ; Lianhua WEI ; Fengmei ZOU ; Yan JIN ; Chunhong SHAO ; Jihong LI ; Lixia ZHANG ; Juan MA ; Yunzhuo CHU ; Sufei TIAN ; Jinju DUAN ; Jianbang KANG ; Ruizhong WANG ; Hua FANG ; Fangfang HU ; Yunjian HU ; Xiaoman AI ; Fang DONG ; Zhiyong LÜ ; Hong ZHANG ; Chun WANG ; Yong ZHAO ; Ping GONG ; Lei ZHU ; Jinhua MENG ; Xiaobo MA ; Yanping ZHENG ; Jinsong WU ; Yuemei LU ; Ruyi GUO ; Yan ZHU ; Kaizhen WEN ; Yirong ZHANG ; Chunlei YUE ; Jiangshan LIU ; Wenhui HUANG ; Shunhong XUE ; Xuefei HU ; Hongqin GU ; Jiao FENG ; Shuping ZHOU ; Yan ZHOU ; Yunsheng CHEN ; Qing MENG ; Bixia YU ; Jilu SHEN ; Rui DOU ; Shifu WANG ; Wen HE ; Longfeng LIAO ; Lin JIANG
Chinese Journal of Infection and Chemotherapy 2024;24(3):309-317
Objective To examine the changing antimicrobial resistance profile of Enterobacter spp.isolates in 53 hospitals across China from 2015 t0 2021.Methods The clinical isolates of Enterobacter spp.were collected from 53 hospitals across China during 2015-2021 and tested for antimicrobial susceptibility using Kirby-Bauer method or automated testing systems according to the CHINET unified protocol.The results were interpreted according to the breakpoints issued by the Clinical & Laboratory Standards Institute(CLSI)in 2021(M100 31st edition)and analyzed with WHONET 5.6 software.Results A total of 37 966 Enterobacter strains were isolated from 2015 to 2021.The proportion of Enterobacter isolates among all clinical isolates showed a fluctuating trend over the 7-year period,overall 2.5%in all clinical isolates amd 5.7%in Enterobacterale strains.The most frequently isolated Enterobacter species was Enterobacter cloacae,accounting for 93.7%(35 571/37 966).The strains were mainly isolated from respiratory specimens(44.4±4.6)%,followed by secretions/pus(16.4±2.3)%and urine(16.0±0.9)%.The strains from respiratory samples decreased slightly,while those from sterile body fluids increased over the 7-year period.The Enterobacter strains were mainly isolated from inpatients(92.9%),and only(7.1±0.8)%of the strains were isolated from outpatients and emergency patients.The patients in surgical wards contributed the highest number of isolates(24.4±2.9)%compared to the inpatients in any other departement.Overall,≤ 7.9%of the E.cloacae strains were resistant to amikacin,tigecycline,polymyxin B,imipenem or meropenem,while ≤5.6%of the Enterobacter asburiae strains were resistant to these antimicrobial agents.E.asburiae showed higher resistance rate to polymyxin B than E.cloacae(19.7%vs 3.9%).Overall,≤8.1%of the Enterobacter gergoviae strains were resistant to tigecycline,amikacin,meropenem,or imipenem,while 10.5%of these strains were resistant to polycolistin B.The overall prevalence of carbapenem-resistant Enterobacter was 10.0%over the 7-year period,but showing an upward trend.The resistance profiles of Enterobacter isolates varied with the department from which they were isolated and whether the patient is an adult or a child.The prevalence of carbapenem-resistant E.cloacae was the highest in the E.cloacae isolates from ICU patients.Conclusions The results of the CHINET Antimicrobial Resistance Surveillance Program indicate that the proportion of Enterobacter strains in all clinical isolates fluctuates slightly over the 7-year period from 2015 to 2021.The Enterobacter strains showed increasing resistance to multiple antimicrobial drugs,especially carbapenems over the 7-year period.