儿童恶性血液病合并医院获得性肺炎的抗生素疗效分析
Analysis of Antibiotic Efficacy in Children with Tumor of the Hematopoietic and Lymphoid Tissues Complicated with Hospital Acquired Pneumonia

作者: 常 瑜 , 林荣军 :青岛大学附属医院综合儿科,山东 青岛;

关键词: 儿童恶性血液病医院获得性肺炎抗生素Children Tumor of the Hematopoietic and Lymphoid Tissues Hospital Acquired Pneumonia Antibiotics

摘要:
目的:探讨美罗培南和哌拉西林/他唑巴坦在治疗恶性血液病患儿合并医院获得性肺炎抗生素的疗效,并对其进行安全性分析,为临床用药提供参考。方法:采用回顾性调查分析自2017年1月至2019年9月期间共60例恶性血液病患儿合并医院获得性肺炎的临床资料,根据所用抗生素种类不同分为观察组和对照组。观察组应用美罗培南,共34例;对照组应用哌拉西林/他唑巴坦,共26例;观察两种抗生素的临床疗效及不良反应。结果:两组患儿治疗总有效率观察组为75.3%、对照组为53.8%,两组差异无统计学意义。结论:美罗培南及哌拉西林/他唑巴坦治疗恶性血液病合并医院获得性肺炎在疗效上没有明显差异,均在临床治疗中不良反应较少。

Abstract: Objective: To evaluate the efficacy and safety of Meropenem and Piperacillin Tazobactam in the treatment of hospital acquired pneumonia in children with tumor of the hematopoietic and lymphoid tissues. Methods: A retrospective study was conducted to analyze the clinical data of 60 children with tumor of the hematopoietic and lymphoid tissues pneumonia from January 2017 to September 2019. The patients were divided into observation group and control group according to the type of antibiotics used. In the observation group, 34 cases were treated with Meropenem; in the control group, 26 cases were treated with Piperacillin/tazobactam. Results: The total effective rate of the two groups was 75.3% in the observation group and 53.8% in the control group. Conclusion: There is no significant difference between Meropenem and Piperacillin Tazobactam in the treatment of tumor of the hematopoietic and lymphoid tissues associated with hospital acquired pneumonia and there are fewer adverse reactions in clinical treatment.

1. 引言

恶性血液病患儿因自身疾病、化疗药物及糖皮质激素的应用等因素,患儿骨髓抑制,粒细胞水平降低,免疫功能不全,导致各种感染机会增加。根据相关研究 [1] [2] [3] 院内呼吸道感染为感染最多部位,其中医院获得性肺炎是化疗后较常见的呼吸道感染疾病,且死亡率较高。并且影响血液病患儿原发病的康复,甚至成为血液病群体的终末感染 [4]。因此选择相应的抗生素在控制感染方面显得尤为重要。本研究选取了近3年来血液儿科恶性血液病合并医院获得性肺炎患儿60例来分析美罗培南和哌拉西林/他唑巴坦对其的治疗效果,为临床应用提供依据。

2. 材料与方法

2.1. 一般资料

2017年1月~2019年12月共收治60例恶性血液病患儿合并医院获得性肺炎,其中急性白血病42例(70%),淋巴瘤17例(28.3%),慢性白血病1例(1.7%)。其中女性患儿24例(40%),男性患儿36例(60%)。患儿年龄(5.35 ± 3.25)岁。入院后发热时间(13.23 ± 5.71)天。

2.2. 诊断标准

医院获得性肺炎诊断标准符合中华医学会制定的《儿童医院获得性肺炎管理方案(2010版)》 [5]。所有患儿均入院时不存在也不处于潜伏期而在入院 > 48 h发生的感染性肺炎。

2.3. 研究方法

此次研究为回顾性分析,本着知情同意的原则,已签署《知情同意书》。将所有患儿根据应用抗生素不同分为观察组予美罗培南按剂量10~20 mg/kg,q8h给药;对照组采用以哌拉西林/他唑巴坦按50~100 mg/kg,q8h给药。对照组与观察组分别有26例和34例。

2.4. 疗效判断标准

详细观察患儿的症状、体征,观察两组患儿的抗生素使用时间、感染控制时间;用药前及停药后检查血常规、肝肾功能,并进行细菌培养。参照《抗菌药物临床应用指导原则》 [6] 的标准评估临床疗效,痊愈:症状、体征、实验室检查和病原学4项均恢复正常;显效:病情明显好转,但上述4项有1项未完全恢复正常;进步:用药后有好转,尚未达到显效标准;无效:用药72 h后病情无明显进步或有加重者。痊愈和显效合计为总有效率。

2.5. 临床表现

57例(95%)患儿出现发热,54例(90%)患儿出现咳嗽,12例(20%)患儿肺部出现湿啰音,4例(6.7%)患儿出现气促。

2.6. 病原学分布

所有患者均送血培养或痰培养,共检出病原菌6株;其中2例大肠埃希菌阳性,1例肺炎克雷伯杆菌阳性;1例阴沟肠杆菌阳性;1例金黄色葡萄球菌阳性;1例凝固酶阴性葡萄球菌阳性。

2.7. 影像学检查

其中36例(60%)胸片及肺部CT示肺部炎症改变,其中双侧肺部病变19例(31.7%),右肺病变11例(18.3%),左肺病变6例(10%);影像学大致正常24例(40%)。

2.8. 中性粒细胞数

55例(91.7%)患儿外周血中性粒细胞计数 < 1.5 × 10^9/L,其中48例(80%)患儿中性粒细胞绝对计数 < 0.5 × 10^9/L。

2.9. 统计学方法

应用SPSS25统计软件进行数据分析,正态计量资料用 x ¯ ± s 表示,组间比较采用t检验;计数资料及率组间比较采用χ2检验,P < 0.05为差异有统计学意义。

3. 结果

3.1. 临床疗效比较

患儿治疗总有效率观察组为75.3%,对照组为53.8%,两组差异无统计学意义(χ2 = 2.568, P = 0.109 > 0.05),见表1。两组临床治疗情况如表2所示,观察组感染控制时间为(5.18 ± 4.56)天,对照组组感染控制时间为(6.15 ± 4.44)天(F = 0.105, t = 0.83, P = 0.41 > 0.05);观察组抗生素使用时间(15.00 ± 4.41)天,对照组抗生素使用时间(16.65 ± 5.78)天(F = 2.91, t = 1.258, P = 0.214 > 0.05),两组差异无统计学意义。

Table 1. Comparison of clinical therapeutic efficiency (%) between the two groups

表1. 2组患儿临床治疗疗效率(%)比较

Table 2. Comparison of clinical treatment between two groups of children

表2. 2组患儿临床治疗情况比较

3.2. 性别、年龄、基础疾病

实验组中男孩22例,女孩12例,患儿年龄(4.85 ± 2.93)岁,基础疾病类型其中急性白血病24例,非急性白血病10例;对照组中男孩14例,女孩12例,患儿年龄(5.74 ± 3.45)岁,基础疾病类型其中急性白血病18例,非急性白血病8例。2组患儿性别(P = 0.395)、年龄(P = 0.297)、基础疾病类型(P = 0.779)等情况比较,对抗生素治疗效果均无显著性差异(P > 0.05)。

3.3. 不良反应

两组患儿均未出现明显的肝肾功损害及过敏表现。

4. 讨论

儿童因自身免疫力较弱,容易感染,且因呼吸系统生理学因素,呼吸道感染尤为常见 [7]。恶性血液病患儿因疾病本身及化疗后骨髓抑制,导致中性粒细胞计数降低,免疫功能受损;加之长期应用糖皮质激素,免疫抑制;又因化疗因素住院治疗时间较长,不可避免地出现院内感染 [8],其中医院获得性肺炎最为常见 [2],且死亡率最高 [9]。国内外大量研究 [3] [7] [10] [11] [12] [13] 证明此类肺炎多因革兰阴性杆菌感染所致,因此在病程初期选用革兰阴性杆菌敏感的广谱抗生素可迅速控制感染 [14],避免病情恶化,改善肺炎的结局。医院获得性肺炎多由耐药性增强的病原体引起的感染 [15] [16] [17] [18] [19],选择有效且安全的抗生素,避免临床应用中抗生素的滥用,所致的细菌耐药性增加 [20] [21]。

美罗培南和哌拉西林/他唑巴坦均属于β内酰胺类抗生素。美罗培南是碳青霉烯类抗生素,具有超广谱、极强的抗菌活性,对β-内酰胺酶有高度的稳定性,因此是临床上治疗恶性血液病患儿重症感染及复杂感染有效药物 [22]。哌拉西林为半合成青霉素类抗生素,他唑巴坦为β内酰胺酶抑制剂;该药物是目前临床上院内感染常用抗生素,其主要是对大多数质粒介导的产和不产β内酰胺酶的细菌大肠埃希菌、克雷伯菌属及链球菌属等,有较高敏感度。此次研究中美罗培南和哌拉西林/他唑巴坦两组药物的总有效率分别为73.5%和53.8%,感染控制时间分别为(5.18 ± 4.56)天和(6.15 ± 4.44)天,在统计学上临床治疗效果未见明显差异。因两种药物均为广谱抗生素,可覆盖院内感染大多数细菌。且与当前碳青霉烯类抗生素使用量增加,导致革兰阴性杆菌对其耐药性上升有关,这与国内外相关的研究 [23] [24] [25] [26] [27] 相符。国内外相关报道 [28] [29] 在临床治疗中美罗培南目前仍是院内重症及复杂感染经验性治疗的首选抗菌药物,因大肠埃希菌及肺炎克雷伯杆菌等对其耐药率较低,这与有些国外相关报道 [30] 不符。有相关研究发现革兰氏阳性球菌在恶性血液病合并院内感染中所占比较前增加 [31],临床应用更加注重病原体类型的辨别。也有国外研究 [32] 报道显示应用碳青霉烯类抗菌药物治疗与采用含酶抑制剂类抗生素经验性治疗的有效率比较差异无统计学意义。结合国内外研究 [28] [33],研究结果提示初始经验治疗时可考虑交替应用以上两种药物,减缓碳青霉烯类抗菌药物耐药菌产生。美罗培南及哌拉西林/他唑巴坦钠在临床应用上不良反应均较少,两组患儿均无明显肝肾功受损及过敏反应。本研究证实,美罗培南和哌拉西林/他唑巴坦治疗恶性血液病合并医院获得性肺炎,疗效确切,且安全稳定。

文章引用: 常 瑜 , 林荣军 (2020) 儿童恶性血液病合并医院获得性肺炎的抗生素疗效分析。 临床医学进展, 10, 2133-2138. doi: 10.12677/ACM.2020.109921

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