Background Evidence is limited about the comparative safety of antibiotic regimens for treatment of community-acquired pneumonia (CAP). We compared the risk of adverse drug events (ADEs) associated with antibiotic regimens for CAP treatment among otherwise healthy, non-elderly adults. Methods We conducted an active comparator new-user cohort study (2007-2019) of commercially-insured adults 18–64 years diagnosed with outpatient CAP, evaluated via chest x-ray, and dispensed a same-day CAP-related oral antibiotic regimen. ADE follow-up duration ranged from 2–90 days (e.g., renal failure [14 days]). We estimated risk differences [RD] per 100 treatment episodes and risk ratios using propensity score weighted Kaplan-Meier functions. Ankle/knee sprain and influenza vaccination were considered as negative control outcomes. Results Of 145,137 otherwise healthy CAP patients without comorbidities, 52% received narrow-spectrum regimens (44% macrolide, 8% doxycycline) and 48% received broad-spectrum regimens (39% fluoroquinolone, 7% β-lactam, 3% β-lactam + macrolide). Compared to macrolide monotherapy, each broad-spectrum antibiotic regimen was associated with increased risk of several ADEs (e.g., β-lactam: nausea/vomiting/abdominal pain [RD per 100, 0.32; 95% CI, 0.10–0.57]; non-Clostridioides difficile diarrhea [RD per 100, 0.46; 95% CI, 0.25–0.68]; vulvovaginal candidiasis/vaginitis [RD per 100, 0.36; 95% CI, 0.09–0.69]). Narrow-spectrum antibiotic regimens largely conferred similar risk of ADEs. We generally observed similar risks of each negative control outcome, indicating minimal confounding. Conclusions Broad-spectrum antibiotics were associated with increased risk of ADEs among otherwise healthy adults treated for CAP in the outpatient setting. Antimicrobial stewardship is needed to promote judicious use of broad-spectrum antibiotics and ultimately decrease antibiotic-related ADEs.

中文翻译：

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不同抗生素方案治疗其他方面健康的成人门诊社区获得性肺炎的比较安全性


背景 关于抗生素方案治疗社区获得性肺炎 （CAP） 的相对安全性的证据有限。我们比较了其他方面健康的非老年人中与抗生素方案治疗 CAP 相关的药物不良事件 （ADE） 风险。方法 我们对被诊断为门诊 CAP 的 18-64 岁商业保险成年人进行了一项主动对照新用户队列研究 （2007-2019），通过胸部 X 光片进行评估，并配发当天与 CAP 相关的口服抗生素方案。ADE 随访持续时间为 2-90 天 （例如，肾功能衰竭 [14 天]）。我们使用倾向评分加权 Kaplan-Meier 函数估计每 100 次治疗事件的风险差异 [RD] 和风险比。踝关节/膝关节扭伤和流感疫苗接种被认为是阴性对照结局。结果 在 145,137 例其他方面健康且无合并症的 CAP 患者中，52% 接受窄谱方案 （44% 大环内酯类，8% 多西环素），48% 接受广谱方案 （39% 氟喹诺酮类、7% β-内酰胺类药物、3% β-内酰胺类 + 大环内酯类药物）。与大环内酯类单药治疗相比，每种广谱抗生素方案都与多种 ADE 的风险增加相关（例如，β-内酰胺类药物：恶心/呕吐/腹痛 [RD/100,0.32;95% CI，0.10-0.57];非艰难梭菌腹泻 [RD/100,0.46;95% CI，0.25-0.68];外阴阴道念珠菌病/阴道炎 [RD/100,0.36;95% CI，0.09-0.69]）。窄谱抗生素方案在很大程度上赋予了类似的 ADE 风险。我们通常观察到每个阴性对照结局的风险相似，表明混杂最小。结论 广谱抗生素与门诊接受 CAP 治疗的健康成人 ADEs 风险增加相关。 需要抗菌药物管理以促进广谱抗生素的明智使用并最终减少与抗生素相关的 ADE。