Association of Broad-vs Narrow-Spectrum Antibiotics With Treatment Failure, Adverse Events, and Quality of Life in Children With Acute Respiratory Tract Infections
Association of Broad-vs Narrow-Spectrum Antibiotics With Treatment Failure, Adverse Events, and Quality of Life in Children With Acute Respiratory Tract Infections
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DOI：
10.1001/jama.2017.18715
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发表时间：
2017-12-19
影响因子：
120.7
通讯作者：
Fiks, Alexander G.
中科院分区：
文献类型：
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作者：
Gerber, Jeffrey S.;Ross, Rachael K.;Fiks, Alexander G.
重要性急性呼吸道感染占儿童抗生素暴露的大部分，治疗急性呼吸道感染的广谱抗生素处方正在增加。目前尚不清楚广谱治疗与窄谱治疗相比是否与改善预后有关。目的比较广谱和窄谱抗生素治疗儿童急性呼吸道感染的有效性。设计、设置和参与者在宾夕法尼亚州和新泽西州31个儿科初级保健实践网络中，设计一项评估临床结果的回顾队列研究和一项前瞻性队列研究，评估2015年1月至2016年4月期间被诊断为急性呼吸道感染并开出口服抗生素的6个月至12岁儿童的以患者为中心的结果。对这两个队列分别进行了分层和倾向评分匹配分析，以说明临床医生和患者水平特征的混淆。EXPOSURES广谱抗生素与窄谱抗生素。在回溯性队列中，主要结果是诊断后14天的治疗失败和不良事件。结果30 159名儿童(急性中耳炎19 179例，A组链球菌性咽炎6746例，急性鼻窦炎4234例)中，4307例(14%)应用了广谱抗生素，包括阿莫西林-克拉维酸、头孢菌素和大环内酯类抗生素。广谱治疗与较低的治疗失败率无关(广谱抗生素为3.4%，窄谱抗生素为3.1%；完全匹配分析的风险差异为0.3%[95%CI，-0.4%至0.9%])。在前瞻性队列中登记的2472名儿童(1100名急性中耳炎；705名A组链球菌性咽炎；667名急性鼻窦炎)中，868名(35%)服用了广谱抗生素。广谱抗生素与儿童生活质量略差有关(广谱抗生素得分为90.2，窄谱抗生素得分为91.5；完全匹配分析得分差异为-1.4%[95%CI，-2.4%至-0.4%])，但与其他以患者为中心的结果无关。广谱治疗与临床医生记录的较高的不良事件风险相关(广谱抗生素为3.7%，窄谱抗生素为2.7%；完全匹配分析的风险差异为1.1%[95%CI，0.4%至1.8%])，并由患者报告(广谱抗生素为35.6%，窄谱抗生素为25.1%；完全匹配分析的风险差异为12.2%[95%CI，7.3%比17.2%])。结论在急性呼吸道感染的儿童中，广谱抗生素与窄谱抗生素相比没有更好的临床或以患者为中心的预后，而与更高的不良事件发生率相关。这些数据支持对大多数患有急性呼吸道感染的儿童使用窄谱抗生素。
IMPORTANCE Acute respiratory tract infections account for the majority of antibiotic exposure in children, and broad-spectrum antibiotic prescribing for acute respiratory tract infections is increasing. It is not clear whether broad-spectrum treatment is associated with improved outcomes compared with narrow-spectrum treatment.OBJECTIVE To compare the effectiveness of broad-spectrum and narrow-spectrum antibiotic treatment for acute respiratory tract infections in children.DESIGN, SETTING, AND PARTICIPANTS A retrospective cohort study assessing clinical outcomes and a prospective cohort study assessing patient-centered outcomes of children between the ages of 6 months and 12 years diagnosed with an acute respiratory tract infection and prescribed an oral antibiotic between January 2015 and April 2016 in a network of 31 pediatric primary care practices in Pennsylvania and New Jersey. Stratified and propensity score-matched analyses to account for confounding by clinician and by patient-level characteristics, respectively, were implemented for both cohorts.EXPOSURES Broad-spectrum antibiotics vs narrow-spectrum antibiotics.MAIN OUTCOMES AND MEASURES In the retrospective cohort, the primary outcomes were treatment failure and adverse events 14 days after diagnosis. In the prospective cohort, the primary outcomes were quality of life, other patient-centered outcomes, and patient-reported adverse events.RESULTS Of 30 159 children in the retrospective cohort (19 179 with acute otitis media; 6746, group A streptococcal pharyngitis; and 4234, acute sinusitis), 4307 (14%) were prescribed broad-spectrum antibiotics including amoxicillin-clavulanate, cephalosporins, and macrolides. Broad-spectrum treatment was not associated with a lower rate of treatment failure (3.4% for broad-spectrum antibiotics vs 3.1% for narrow-spectrum antibiotics; risk difference for full matched analysis, 0.3%[95% CI, -0.4% to 0.9%]). Of 2472 children enrolled in the prospective cohort (1100 with acute otitis media; 705, group A streptococcal pharyngitis; and 667, acute sinusitis), 868 (35%) were prescribed broad-spectrum antibiotics. Broad-spectrum antibiotics were associated with a slightly worse child quality of life (score of 90.2 for broad-spectrum antibiotics vs 91.5 for narrow-spectrum antibiotics; score difference for full matched analysis, -1.4%[95% CI, -2.4% to -0.4%]) but not with other patient-centered outcomes. Broad-spectrum treatment was associated with a higher risk of adverse events documented by the clinician (3.7% for broad-spectrum antibiotics vs 2.7% for narrow-spectrum antibiotics; risk difference for full matched analysis, 1.1% [95% CI, 0.4% to 1.8%]) and reported by the patient (35.6% for broad-spectrum antibiotics vs 25.1% for narrow-spectrum antibiotics; risk difference for full matched analysis, 12.2%[95% CI, 7.3% to 17.2%]).CONCLUSIONS AND RELEVANCE Among children with acute respiratory tract infections, broad-spectrum antibiotics were not associated with better clinical or patient-centered outcomes compared with narrow-spectrum antibiotics, and were associated with higher rates of adverse events. These data support the use of narrow-spectrum antibiotics for most children with acute respiratory tract infections.