目的:探讨莫西沙星单药治疗无铜绿假单胞菌感染危险因素的慢性阻塞性肺疾病急性加重期患者的临床应用价值,评价其疗效和安全性。方法:采用随机、对照的研究方法,选取2018年12月至2020年1月于山西医科大学附属汾阳医院呼吸与危重症医学科及老年医学科住院的慢性阻塞性肺疾病急性加重期患者130例,随机分为实验组及对照组,分别在基础治疗,包括呼吸支持、糖皮质激素、支气管舒张剂及祛痰等辅助药物治疗上加用莫西沙星及阿莫西林/克拉维酸,治疗后评价其疗效及实验室指标。结果:临床疗效方面,实验组有效率81.5%,对照组有效率73.8%,差异无统计学意义(X2值1.110、P = 0.292)。实验室指标方面,治疗后白细胞计数实验组(6.78 ± 2.23) × 109/L,对照组(7.81 ± 2.86) × 109/L,差异有统计学意义(t值−2.282,P = 0.024)。治疗后的降钙素原实验组(0.154 ± 0.195) ng/ml,对照组(0.239 ± 235) ng/ml,差异有统计学意义(t值−2.240,P = 0.027)。存在II型呼吸衰竭患者PCO2治疗前后变化值实验组(20.62 ± 6.40) mmHg优于对照组(13.93 ± 9.26) mmHg,差异有统计学意义(t值2.570、P = 0.015)。实验组FEV1/pred治疗后(63.59 ± 13.56)%,对照组(54.43 ± 12.57)%;差异有统计学意义(t值3.998、P < 0.001)。实验组FEV1/FVC治疗后(55.16 ± 8.76) %,对照组(51.26 ± 10.24)%,差异有统计学意义(t值2.335、P = 0.021)。抗生素使用时间及平均住院时间实验组[(6.75 ± 1.94)、(9.78 ± 2.40)]d均低于对照组[(8.85 ± 1.99)、(11.37 ± 2.56)]d,差异有统计学意义(t值−6.081、−3.679,均P < 0.001)。随访6个月内的急性加重情况,差异无统计学意义(X2值0.074、P = 0.785)。结论:莫西沙星可以用于治疗无铜绿假单胞菌感染危险因素的慢性阻塞性肺疾病急性加重期患者,有着更好的肺功能改善,更短的抗菌药物使用时间及住院时间,在合并II型呼吸衰竭亚组中更有优势,安全性好。 Objective: To evaluate the efficacy and safety of moxifloxacin monotherapy in patients with acute exacerbation of chronic obstructive pulmonary disease without risk factors of Pseudomonas aeruginosa infection. Methods: A total of 130 patients with acute exacerbation of chronic obstructive pulmonary disease who were hospitalized in Department of Respiratory and Critical Care Medicine and Department of Geriatrics, Affiliated Fenyang Hospital of Shanxi Medical University from December 2018 to January 2020 were randomly divided into experimental group and control group, who received basic treatment respectively. Moxifloxacin and amoxicillin/clavulanate were added to respiratory support, systemic corticosteroids, bronchodilators, expectorants and other adjuvant medications. The efficacy and laboratory indicators were evaluated after treatment. Results: In terms of clinical efficacy, the effective rate was 81.5% in the experimental group and 73.8% in the control group, the difference was not statistically significant (X2 = 1.110, P = 0.292). In terms of laboratory indicators, the white blood cell count in the experimental group after treatment was (6.78 ± 2.23) × 109/L, control group (7.81 ± 2.86) × 109/L, the difference was statistically significant (t value −2.282, P = 0.024). Procalcitonin group after treatment (0.154 ± 0.195) ng/ml, control group (0.239 ± 235) ng/ml, the difference was statistically significant (t value −2.240, P = 0.027). The change of PCO2 in patients with II type respiratory failure before and after treatment in the experimental group (20.62 ± 6.40) mmHg was better than that in the control group (13.93 ± 9.26) mmHg, the difference was statistically significant (t value 2.570, P = 0.015). After treatment, FEV1/pred was (63.59 ± 13.56)% in the experimental group and (54.43 ± 12.57)% in the control group. The difference was statistically significant (t value 3.998, P < 0.001). In the experimental group, FEV1/FVC was (55.16 ± 8.76)% after treatment, control group (51.26 ± 10.24)%, the difference was statistically significant (t value 2.335, P = 0.021). The duration of antibiotic use and average length of hospital stay in the experimental group [(6.75 ± 1.94), (9.78 ± 2.40)]d were lower than those in the control group [(8.85 ± 1.99), (11.37 ± 2.56)]d. The difference was statistically significant (t value −6.081, −3.679, all P < 0.001). There was no significant difference in acute exacerbation during the follow-up period of 6 months (X2 = 0.074, P = 0.785). Conclusion: Moxifloxacin can be used to treat patients with acute exacerbation of COPD without risk factors for Pseudomonas aeruginosa infection, with the better improvement of lung function, shorter duration of antibiotic use and hospital stay. It is more advantageous in the subgroup of combined II type respiratory failure and has good safety.
目的:探讨莫西沙星单药治疗无铜绿假单胞菌感染危险因素的慢性阻塞性肺疾病急性加重期患者的临床应用价值,评价其疗效和安全性。方法:采用随机、对照的研究方法,选取2018年12月至2020年1月于山西医科大学附属汾阳医院呼吸与危重症医学科及老年医学科住院的慢性阻塞性肺疾病急性加重期患者130例,随机分为实验组及对照组,分别在基础治疗,包括呼吸支持、糖皮质激素、支气管舒张剂及祛痰等辅助药物治疗上加用莫西沙星及阿莫西林/克拉维酸,治疗后评价其疗效及实验室指标。结果:临床疗效方面,实验组有效率81.5%,对照组有效率73.8%,差异无统计学意义(c2值1.110、P = 0.292)。实验室指标方面,治疗后白细胞计数实验组(6.78 ± 2.23) × 109/L,对照组(7.81 ± 2.86) × 109/L,差异有统计学意义(t值−2.282,P = 0.024)。治疗后的降钙素原实验组(0.154 ± 0.195) ng/ml,对照组(0.239 ± 235) ng/ml,差异有统计学意义(t值−2.240,P = 0.027)。存在II型呼吸衰竭患者PCO2治疗前后变化值实验组(20.62 ± 6.40) mmHg优于对照组(13.93 ± 9.26) mmHg,差异有统计学意义(t值2.570、P = 0.015)。实验组FEV1/pred治疗后(63.59 ± 13.56)%,对照组(54.43 ± 12.57)%;差异有统计学意义(t值3.998、P < 0.001)。实验组FEV1/FVC治疗后(55.16 ± 8.76) %,对照组(51.26 ± 10.24)%,差异有统计学意义(t值2.335、P = 0.021)。抗生素使用时间及平均住院时间实验组[(6.75 ± 1.94)、(9.78 ± 2.40)]d均低于对照组[(8.85 ± 1.99)、(11.37 ± 2.56)]d,差异有统计学意义(t值−6.081、−3.679,均P < 0.001)。随访6个月内的急性加重情况,差异无统计学意义(c2值0.074、P = 0.785)。结论:莫西沙星可以用于治疗无铜绿假单胞菌感染危险因素的慢性阻塞性肺疾病急性加重期患者,有着更好的肺功能改善,更短的抗菌药物使用时间及住院时间,在合并II型呼吸衰竭亚组中更有优势,安全性好。
莫西沙星,慢性阻塞性肺疾病,无铜绿假单胞菌感染危险因素
Cong Deng1*, Xiaohong Cao2, Lele Zhao1, Siwei Zhao1, Yonghong Liu1, Liqin Zheng3#
1Graduate College, Shanxi Medical University, Taiyuan Shanxi
2Department of Geriatrics, Fenyang Hospital Affiliated to Shanxi Medical University, Fenyang Shanxi
3Respiratory Department, Fenyang Hospital Affiliated to Shanxi Medical University, Fenyang Shanxi
Received: Jun. 19th, 2021; accepted: Jul. 15th, 2021; published: Jul. 23rd, 2021
Objective: To evaluate the efficacy and safety of moxifloxacin monotherapy in patients with acute exacerbation of chronic obstructive pulmonary disease without risk factors of Pseudomonas aeruginosa infection. Methods: A total of 130 patients with acute exacerbation of chronic obstructive pulmonary disease who were hospitalized in Department of Respiratory and Critical Care Medicine and Department of Geriatrics, Affiliated Fenyang Hospital of Shanxi Medical University from December 2018 to January 2020 were randomly divided into experimental group and control group, who received basic treatment respectively. Moxifloxacin and amoxicillin/clavulanate were added to respiratory support, systemic corticosteroids, bronchodilators, expectorants and other adjuvant medications. The efficacy and laboratory indicators were evaluated after treatment. Results: In terms of clinical efficacy, the effective rate was 81.5% in the experimental group and 73.8% in the control group, the difference was not statistically significant (c2 = 1.110, P = 0.292). In terms of laboratory indicators, the white blood cell count in the experimental group after treatment was (6.78 ± 2.23) × 109/L, control group (7.81 ± 2.86) × 109/L, the difference was statistically significant (t value −2.282, P = 0.024). Procalcitonin group after treatment (0.154 ± 0.195) ng/ml, control group (0.239 ± 235) ng/ml, the difference was statistically significant (t value −2.240, P = 0.027). The change of PCO2 in patients with II type respiratory failure before and after treatment in the experimental group (20.62 ± 6.40) mmHg was better than that in the control group (13.93 ± 9.26) mmHg, the difference was statistically significant (t value 2.570, P = 0.015). After treatment, FEV1/pred was (63.59 ± 13.56)% in the experimental group and (54.43 ± 12.57)% in the control group. The difference was statistically significant (t value 3.998, P < 0.001). In the experimental group, FEV1/FVC was (55.16 ± 8.76)% after treatment, control group (51.26 ± 10.24)%, the difference was statistically significant (t value 2.335, P = 0.021). The duration of antibiotic use and average length of hospital stay in the experimental group [(6.75 ± 1.94), (9.78 ± 2.40)]d were lower than those in the control group [(8.85 ± 1.99), (11.37 ± 2.56)]d. The difference was statistically significant (t value −6.081, −3.679, all P < 0.001). There was no significant difference in acute exacerbation during the follow-up period of 6 months (c2 = 0.074, P = 0.785). Conclusion: Moxifloxacin can be used to treat patients with acute exacerbation of COPD without risk factors for Pseudomonas aeruginosa infection, with the better improvement of lung function, shorter duration of antibiotic use and hospital stay. It is more advantageous in the subgroup of combined II type respiratory failure and has good safety.
Keywords:Moxifloxacin, Chronic Obstructive Pulmonary Disease, Risk Factors without Pseudomonas aeruginosa Infection
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慢性阻塞性肺疾病(慢阻肺,chronic obstructive pulmonary disease, COPD)多与有害颗粒或有害气体引起的气道和(或)肺泡异常炎症反应有关。来自阻塞性肺病负担研究BOLD和其他大型流行病学研究显示,估计全球慢阻肺患者达3.84亿 [
这是一项前瞻性的病例对照研究,研究对象为2018年12月至2020年1月于山西医科大学附属汾阳医院呼吸与危重症医学科及老年医学科住院的慢性阻塞性肺疾病急性加重期患者,根据2018年GOLD [
1) 年龄 ≥ 60岁,需住院治疗的AECOPD患者,符合下列条件之一 [
1) 合并肺炎、急性支气管炎、肺脓肿;2) 对青霉素类及喹诺酮类抗菌药过敏;3) 严重心、肝、肾功能不全;4) 入住重症病房需有创呼吸机辅助通气支持;5) 合并恶性肿瘤;6) 其他系统存在严重且未控制的疾病。
我们把AECOPD患者随机分为两组,实验组静脉应用莫西沙星(400 mg qd),对照组静脉应用阿莫西林/克拉维酸(1000/200 mg q8h)。两组均给予基础治疗,包括呼吸支持(鼻导管、面罩、高流量)、糖皮质激素、支气管舒张剂及祛痰等辅助药物治疗。
目前尚无统一评价患者出院及好转的标准,部分研究以患者症状是否回到基线为主要评价指标,本研究根据慢性阻塞性肺疾病急性加重的定义制定疗效评价标准,以患者的主观感受为主,体征及检查指标为辅。主要标准为出院时痰量、脓痰、呼吸困难症状恢复到基线水平 [
记录所有患者表现出的不良事件症状,由研究者评估不良反应与研究药物是否存在因果关系,并统计比较不良事件发生率。
采用SPSS 22.0软件进行统计分析,计量资料采用 x ¯ ± s 表示,两组比较采用t检验;计数资料采用百分比表示,两组间比较采用c2检验;以P < 0.05为差异有统计学意义。
实验组65例患者,男性37例、女性28例,平均年龄(69.3 ± 8.8)岁;对照组65例患者,男性39例、女性26例,平均年龄(70.0 ± 8.6)岁。两组患者年龄、性别、体质指数、吸烟、上一年度加重次数及入院时呼吸衰竭情况均无统计学意义(表1)。入院时留取治疗前及晨痰标本,治疗3天后评价患者早期临床反应情况,根据患者症状(呼吸困难、痰量、痰液性质)改善情况(表2),共有9例患者因病情加重或需要联用其他抗菌药物而退出研究,实验组和对照组分别为4例和5例退出研究。
基线资料 | 实验组 | 对照组 |
---|---|---|
例数(n) | 65 | 65 |
年龄( x ¯ ± s ,岁) | 69.3 ± 8.8 | 70.0 ± 8.6 |
男性[n (%)] | 37 (57) | 39 (60) |
体质指数( x ¯ ± s , kg/m2) | 22.2 ± 2.9 | 22.6 ± 2.7 |
吸烟[n (%)] | 43 (66) | 41 (63) |
上一年度急性加重情况[n (%)] | 24 (37) | 23 (35) |
---|---|---|
FEV1/FVC ( x ¯ ± s ,%) | 43.8 ± 10.1 | 44.4 ± 9.5 |
呼吸衰竭 | ||
I型呼吸衰竭[n (%)] | 14 (22) | 16 (25) |
II型呼吸衰竭[n (%)] | 19 (29) | 18 (28) |
表1. 基线资料
病原菌 | 实验组 | 对照组 | ||
---|---|---|---|---|
病原菌(株) | 早期临床反应* | 病原菌(株) | 早期临床反应 | |
肺炎链球菌 | 5 | 4 | 6 | 4 |
流感嗜血杆菌 | 3 | 3 | 3 | 3 |
肺炎克雷伯菌 | 2 | 1 | 2 | 1 |
金黄色葡萄球菌 | 2 | 2 | 1 | 1 |
大肠杆菌 | 1 | 1 | 0 | 0 |
合计 | 13 | 11 (84.6) | 12 | 9 (75.0) |
表2. 病原学
注:*表示治疗3天后痰培养阳性患者症状改善情况,采用例数n(%)表示。
实验组(53/65, 81.5%)例有效,12例无效,失败患者中有3例为出院时症状部分好转,8周内再次急性加重;对照组(48/65, 73.8%)例有效,17例无效,其中有5例为出院时症状部分好转,8周内再次急性加重。两组间临床疗效差异无统计学意义(c2值1.110、P = 0.292)。
实验室指标分析了感染指标:白细胞计数、降钙素原;通气功能:二氧化碳分压、FEV1/pred及FEV1/FVC在入院时和第7天的变化情况。
感染指标中白细胞计数:实验组治疗前(10.71 ± 4.30) × 109/L,第7天(6.78 ± 2.23) ×109/L;对照组治疗前(10.47 ± 3.47) ×109/L,第7天(7.81 ± 2.86) × 109/L;两组间治疗后差异有统计学意义(t值−2.282,P=0.024)。降钙素原:实验组治疗前(0.490 ± 0.435) ng/ml,第7天(0.154 ± 0.195) ng/ml;对照组治疗前(0.501 ± 0.500) ng/ml,第7天(0.239 ± 0.235) ng/ml;两组间治疗后差异有统计学意义(t值−2.240,P = 0.027)。
通气功能方面,PCO2:实验组治疗前(46.11 ± 11.45) mmHg,第7天(41.06 ± 5.95) mmHg,治疗前后差值(5.04 ± 13.20) mmHg;对照组治疗前(46.46 ± 10.30) mmHg,第7天(42.86 ± 5.49) mmHg,治疗前后差值(3.60 ± 10.01) mmHg;两组间差异无统计学意义(t值0.73、P = 0.483)。比较两组中发生II型呼吸衰竭患者PCO2变化情况,实验组19例(20.62 ± 6.40) mmHg,对照组18例(13.93 ± 9.26) mmHg;两组间差异有统计学意义(t值2.570、P = 0.015)。FEV1/pred:实验组治疗前(48.87 ± 13.40)%,第7天(63.59 ± 13.56)%;对照组治疗前(48.51 ± 15.86)%,第7天(54.43 ± 12.57)%;两组间治疗后差异有统计学意义(t值3.998、P < 0.001)。FEV1/FVC:实验组治疗前(43.83 ± 10.05)%,第7天(55.16 ± 8.76)%,治疗前后差值(−11.33 ± 12.60)%;对照组治疗前(44.19 ± 9.34)%,第7天(51.26 ± 10.24)%,治疗前后差值(−7.07 ± 9.79)%;两组间差异有统计学意义(t值−2.155、P = 0.033)。
实验组抗菌药物使用时长(6.75 ± 1.94)天,对照组抗菌药物使用时长(8.85 ± 1.99)天;两组间差异有统计学意义(t值−6.081、P < 0.001)。实验组住院时长(9.78 ± 2.40)天,对照组住院时长(11.37 ± 2.56)天;两组间差异有统计学意义(t值−3.679、P < 0.001)。
在6个月的随访过程中(图1) 19例患者失访,失访率小于20%。实验组(15/56, 26.8%)出现急性加重,对照组(16/55, 29.1%)出现急性加重;两组间差异无统计学意义(c2值0.074、P = 0.785)。
图1. 6个月内再次急性加重情况
实验组出现恶心、腹泻消化道症状4例,静脉炎1例;对照组出现恶心症状5例,皮肤瘙痒1例;予以对症治疗后好转,未出现需停药的不良事件。两组间差异无统计学意义(c2值0.099、P = 0.753)。
慢性阻塞性肺疾病是一种常见的以持续性呼吸道症状和气流受限为特征的可以预防和治疗的疾病。GOLD指南给出急性加重的定义为呼吸道症状加重以致需要额外的治疗,治疗主要为氧疗、支气管扩张剂、激素和抗菌药物。Cochrane协作网的研究显示 [
莫西沙星抗菌谱广,对大多数革兰阳性菌、大多数革兰阴性菌、军团菌、支原体、衣原体敏感,涵盖了大部分呼吸道感染的细菌,并且能在肺泡中聚集。相关文献显示 [
山西省卫生计生委员会科研课题(2017188)。
邓 聪,曹晓红,赵乐乐,赵思维,刘永红,郑丽琴. 莫西沙星治疗无铜绿假单胞菌危险因素老年慢性阻塞性肺疾病急性加重期的疗效研究 Clinical Study of Moxifloxacin in the Treatment of Acute Exacerbation of Chronic Obstructive Pulmonary Disease in Elderly Patients without Risk Factors of Pseudomonas aeruginosa Infection[J]. 药物资讯, 2021, 10(04): 230-237. https://doi.org/10.12677/PI.2021.104029