Butler Anne M, Nickel Katelin B, Olsen Margaret A, Sahrmann John M, Colvin Ryan, Neuner Elizabeth, O'Neil Caroline A, Fraser Victoria J, Durkin Michael J
Department of Medicine, Division of Infectious Diseases, Washington University School of Medicine, St. Louis, MO, USA.
Department of Surgery, Division of Public Health Sciences, Washington University School of Medicine, St. Louis, MO, USA.
Clin Infect Dis. 2024 Oct 23. doi: 10.1093/cid/ciae519.
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.
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 1000 treatment episodes and risk ratios using propensity score weighted Kaplan-Meier functions. Ankle/knee sprain and influenza vaccination were considered as negative control outcomes.
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 with macrolide monotherapy, each broad-spectrum antibiotic regimen was associated with increased risk of several ADEs (eg, β-lactam: nausea/vomiting/abdominal pain [RD per 1000, 3.20; 95% CI, 0.99–5.73]; non–Clostridioides difficile diarrhea [RD per 1000, 4.61; 95% CI, 2.47–6.82]; vulvovaginal candidiasis/vaginitis [RD per 1000, 3.57; 95% CI, 0.87, 6.88]). Narrow-spectrum antibiotic regimens largely conferred similar risk of ADEs. We generally observed similar risks of each negative control outcome, indicating minimal confounding.
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.
关于治疗社区获得性肺炎（CAP）的抗生素方案的比较安全性，证据有限。我们比较了在其他方面健康的非老年成年人中，与治疗CAP的抗生素方案相关的药物不良事件（ADE）风险。
我们进行了一项活性对照新使用者队列研究（2007 - 2019年），研究对象为18 - 64岁诊断为门诊CAP的商业保险成年人，通过胸部X线评估，并当日配发与CAP相关的口服抗生素方案。ADE随访持续时间为2 - 90天（例如，肾衰竭[14天]）。我们使用倾向评分加权的Kaplan - Meier函数估计每1000次治疗发作的风险差异[RD]和风险比。脚踝/膝盖扭伤和流感疫苗接种被视为阴性对照结局。
在145137名无合并症的其他方面健康的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，3%β - 内酰胺类 + 大环内酯类）。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风险增加相关（例如，β - 内酰胺类：恶心/呕吐/腹痛[每1000例的RD，3.20；95%CI，0.99 - 5.73]；非艰难梭菌性腹泻[每1000例的RD，4.61；95%CI，2.47 - 6.82]；外阴阴道念珠菌病/阴道炎[每1000例的RD，3.57；95%CI，0.87，6.88]）。窄谱抗生素方案在很大程度上具有相似的ADE风险。我们总体上观察到每个阴性对照结局的风险相似，表明混杂因素最小。
在门诊环境中，广谱抗生素与接受CAP治疗的其他方面健康的成年人中ADE风险增加相关。需要进行抗菌药物管理，以促进广谱抗生素的合理使用，并最终减少与抗生素相关的ADE。
