Objectives

Increasing antimicrobial resistance has renewed interest in older, less used antimicrobials. Cotrimoxazole shows promise; however, hyperkalaemia and acute kidney injury (AKI) are potential complications. Identifying risk factors for and quantification of these events is required for safe use. This study aimed to evaluate predictors of cotrimoxazole-associated AKI and hyperkalaemia in a clinical setting.

Methods

Patients prescribed cotrimoxazole were identified using electronic healthcare records over 3 years (1 April 2016 to 31 March 2019). Individual risk factors were recognized. Serum creatinine and potassium trends were analysed over the subsequent 21 days. AKI and patients with hyperkalaemia were classified using Kidney Disease Improving Global Outcomes (KDIGO) and laboratory criteria. Univariate and multiple logistic regression analyses were performed.

Results

Among 214 patients prescribed cotrimoxazole, 42 (19.6%, 95% confidence interval (CI) 14.6–25.7) met AKI criteria and 33 (15.4%, 95% CI 11.0–21.1) developed hyperkalaemia. Low baseline estimated glomerular filtration rate (<60 mL/min/1.73 m², odds ratio (OR) 7.78, 95% CI 3.57–16.13, p < 0.0001) and cardiac disorders (OR 2.40, 95% CI 1.17–4.82, p 0.011) predicted AKI, while low baseline estimated glomerular filtration rate (<60 mL/min/1.73 m², OR 6.80, 95% CI 3.09–15.06, p < 0.0001) and higher baseline serum potassium (p 0.001) predicted hyperkalaemia. Low-dose cotrimoxazole (<1920 mg/d) was associated with lower AKI and hyperkalaemia risk (p 0.007 and 0.019 respectively). Early (within the first 2–4 days of therapy) serum creatinine changes predicted AKI (OR 3.65, 95% CI 1.73–7.41, p 0.001), and early serum potassium changes predicted hyperkalaemia (>0.6 mmol/L, OR 2.47, 95% CI 1.14–5.27, p 0.0236).

Conclusions

Cotrimoxazole-associated AKI and hyperkalaemia is frequent and dose dependent. Renal function, serum potassium and preexisting cardiac disorders should be evaluated before prescribing cotrimoxazole. Serum creatinine and potassium monitoring within first 2 to 4 days of treatment to identify susceptible patients is recommended, and the lowest effective dose ought to be prescribed.

中文翻译：

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用考特莫唑评估高钾血症和急性肾损伤的风险：一项回顾性观察研究。

目标

越来越多的抗菌素耐药性引起了人们对更古老，使用更少的抗菌素的兴趣。复方新诺明显示出希望；但是，高钾血症和急性肾损伤（AKI）是潜在的并发症。为了安全使用，需要识别这些事件的风险因素并对其进行量化。这项研究旨在评估在临床环境中与卡曲莫唑相关的AKI和高钾血症的预测因素。

方法

使用电子病历在3年中（2016年4月1日至2019年3月31日）确定了处方使用cotrimoxazole的患者。认识到个人危险因素。在随后的21天中分析了血清肌酐和钾的趋势。AKI和高钾血症患者使用肾脏疾病改善全球结局（KDIGO）和实验室标准进行分类。进行了单变量和多元逻辑回归分析。

结果

在214例使用考特莫唑处方的患者中，有42例（19.6％，95％置信区间（CI）14.6–25.7）符合AKI标准，而33例（15.4％，95％CI 11.0–21.1）发生了高钾血症。基线估计肾小球滤过率低（<60 mL / min / 1.73 m ²，比值比（OR）7.78，95％CI 3.57–16.13，p <0.0001）和心脏疾病（OR 2.40，95％CI 1.17–4.82，p 0.011）预测的AKI，而较低的基线估计的肾小球滤过率（<60 mL / min / 1.73 m ²，或6.80，95％CI 3.09-15.06，p <0.0001）和较高的基线血钾（p 0.001）可预测为高钾血症。低剂量甲氧咪唑（<1920 mg / d）与较低的AKI和高钾血症风险相关（分别为0.007和0.019）。早期（治疗的前2-4天）血清肌酐变化可预测AKI（OR 3.65，95％CI 1.73–7.41，p 0.001），早期血清钾变化可预测高钾血症（> 0.6 mmol / L，OR 2.47、95 ％CI 1.14–5.27，第0.0236页）。

结论

复方新诺明相关的AKI和高钾血症很常见且呈剂量依赖性。在开立卡曲美唑之前，应评估肾功能，血钾和先前存在的心脏疾病。建议在治疗的前2至4天内监测血清肌酐和钾，以识别易感患者，并应规定最低有效剂量。