Abstract：
OBJECTIVE: Trimethoprim-sulfamethoxazole (TMP-SMX) may increase digoxin concentration, a medication with a narrow therapeutic index. Small changes in digoxin concentration could predispose individuals to the risk of toxicity.
OBJECTIVE: To characterize the risk of digoxin toxicity in older adults taking digoxin following co-prescription of TMP-SMX compared with co-prescription of amoxicillin.
METHODS: Retrospective population-based cohort study in Ontario, Canada (2002-2020) using linked health care data. Participants comprised 47,961 older adults taking digoxin (58% women; median age 80 years [interquartile range 74-86]) who were newly treated with TMP-SMX (n = 10,273) compared with those newly treated with amoxicillin (n = 37,688).
METHODS: Co-prescription of TMP-SMX versus amoxicillin in older adults concurrently taking digoxin.
METHODS: The primary outcome was a hospital encounter (i.e., hospital admission or emergency department visit) with digoxin toxicity within 30 days of the antibiotic prescription. Inverse probability of treatment weighting on the propensity score was used to balance comparison groups on indicators of baseline health. Weighted risk ratios (RR) were obtained using modified Poisson regression and weighted risk differences (RD) using binomial regression. The number needed to harm (NNH) was calculated as 1/RD.
RESULTS: A hospital encounter with digoxin toxicity occurred in 49/10,273 (0.48%) patients treated with TMP-SMX versus 32/37,688 (0.08%) in those treated with amoxicillin (weighted RR, 5.71 [95% confidence interval (CI), 3.19 to 10.24]; weighted RD, 0.39% [95% CI, 0.25% to 0.53%]; NNH 256 [95% CI, 233 to 400]).
CONCLUSIONS: In older adults taking digoxin, the 30-day risk of a hospital encounter with digoxin toxicity was nearly 6 times higher in those co-prescribed TMP-SMX versus amoxicillin, although the absolute risk difference was low (0.4%). Physicians should prescribe an alternative antibiotic when clinically appropriate. If TMP-SMX must be co-prescribed with digoxin (if the benefit is believed to outweigh the risk), digoxin should be dose-reduced on an individual basis.
OBJECTIVE: To characterize the risk of digoxin toxicity in older adults taking digoxin following co-prescription of TMP-SMX compared with co-prescription of amoxicillin.
METHODS: Retrospective population-based cohort study in Ontario, Canada (2002-2020) using linked health care data. Participants comprised 47,961 older adults taking digoxin (58% women; median age 80 years [interquartile range 74-86]) who were newly treated with TMP-SMX (n = 10,273) compared with those newly treated with amoxicillin (n = 37,688).
METHODS: Co-prescription of TMP-SMX versus amoxicillin in older adults concurrently taking digoxin.
METHODS: The primary outcome was a hospital encounter (i.e., hospital admission or emergency department visit) with digoxin toxicity within 30 days of the antibiotic prescription. Inverse probability of treatment weighting on the propensity score was used to balance comparison groups on indicators of baseline health. Weighted risk ratios (RR) were obtained using modified Poisson regression and weighted risk differences (RD) using binomial regression. The number needed to harm (NNH) was calculated as 1/RD.
RESULTS: A hospital encounter with digoxin toxicity occurred in 49/10,273 (0.48%) patients treated with TMP-SMX versus 32/37,688 (0.08%) in those treated with amoxicillin (weighted RR, 5.71 [95% confidence interval (CI), 3.19 to 10.24]; weighted RD, 0.39% [95% CI, 0.25% to 0.53%]; NNH 256 [95% CI, 233 to 400]).
CONCLUSIONS: In older adults taking digoxin, the 30-day risk of a hospital encounter with digoxin toxicity was nearly 6 times higher in those co-prescribed TMP-SMX versus amoxicillin, although the absolute risk difference was low (0.4%). Physicians should prescribe an alternative antibiotic when clinically appropriate. If TMP-SMX must be co-prescribed with digoxin (if the benefit is believed to outweigh the risk), digoxin should be dose-reduced on an individual basis.
摘要：
目的：甲氧苄啶-磺胺甲恶唑（TMP-SMX）可能会增加地高辛浓度，治疗指数狭窄的药物。地高辛浓度的微小变化可能使个体容易发生毒性风险。
目的：研究TMP-SMX联合处方与阿莫西林联合处方后服用地高辛的老年人发生地高辛毒性的风险。
方法：安大略省基于人群的回顾性队列研究，加拿大(2002-2020年)使用关联医疗保健数据。参与者包括47,961名服用地高辛的老年人（58％为女性；中位年龄80岁[四分位数范围74-86]），他们新接受TMP-SMX治疗（n=10,273），而新接受阿莫西林治疗的人（n=37,688）。
方法：TMP-SMX与阿莫西林在老年人同时服用地高辛的联合处方。
方法：主要结果是住院（即，入院或急诊科就诊）在抗生素处方后30天内出现地高辛毒性。使用倾向评分上的治疗加权的逆概率来平衡基线健康指标上的比较组。使用改进的Poisson回归获得加权风险比（RR），并使用二项回归获得加权风险差（RD）。伤害所需的数量(NNH)计算为1/RD。
结果：TMP-SMX治疗的49/10,273（0.48％）患者与阿莫西林治疗的32/37,688（0.08％）患者（加权RR，5.71[95%置信区间(CI)，3.19至10.24]；加权RD，0.39%[95%CI，0.25%至0.53%]；NNH256[95%CI，233至400]）。
结论：在服用地高辛的老年人中，与阿莫西林相比，共同处方的TMP-SMX在医院遇到地高辛毒性的30天风险高出近6倍，尽管绝对风险差异较低(0.4%).医生应在临床上适当时开一种替代抗生素。如果TMP-SMX必须与地高辛共同处方（如果认为益处大于风险），地高辛应该在个体基础上减少剂量。
目的：研究TMP-SMX联合处方与阿莫西林联合处方后服用地高辛的老年人发生地高辛毒性的风险。
方法：安大略省基于人群的回顾性队列研究，加拿大(2002-2020年)使用关联医疗保健数据。参与者包括47,961名服用地高辛的老年人（58％为女性；中位年龄80岁[四分位数范围74-86]），他们新接受TMP-SMX治疗（n=10,273），而新接受阿莫西林治疗的人（n=37,688）。
方法：TMP-SMX与阿莫西林在老年人同时服用地高辛的联合处方。
方法：主要结果是住院（即，入院或急诊科就诊）在抗生素处方后30天内出现地高辛毒性。使用倾向评分上的治疗加权的逆概率来平衡基线健康指标上的比较组。使用改进的Poisson回归获得加权风险比（RR），并使用二项回归获得加权风险差（RD）。伤害所需的数量(NNH)计算为1/RD。
结果：TMP-SMX治疗的49/10,273（0.48％）患者与阿莫西林治疗的32/37,688（0.08％）患者（加权RR，5.71[95%置信区间(CI)，3.19至10.24]；加权RD，0.39%[95%CI，0.25%至0.53%]；NNH256[95%CI，233至400]）。
结论：在服用地高辛的老年人中，与阿莫西林相比，共同处方的TMP-SMX在医院遇到地高辛毒性的30天风险高出近6倍，尽管绝对风险差异较低(0.4%).医生应在临床上适当时开一种替代抗生素。如果TMP-SMX必须与地高辛共同处方（如果认为益处大于风险），地高辛应该在个体基础上减少剂量。
