Due to increasing antimicrobial resistance, clinicians have returned to using older agents such as cotrimoxazole, a combination of trimethoprim and sulfamethoxazole, to treat patients afflicted with Gram-positive and Gram-negative aerobic bacteria or fungi. Now researchers have identified predictors of acute kidney injury (AKI) or hyperkalemia among cotrimoxazole users.

In a group of 214 patients prescribed cotrimoxazole, AKI and hyperkalemia developed in 19.6% and 15.4% of patients, respectively. Patients with a baseline estimated glomerular filtration rate (eGFR) less than 60 mL/min/1.73 m2 had significant 7.8- and 6.8-fold higher risks for AKI and hyperkalemia, respectively, Stephen Hughes, MPharm, MSc, MBA, of Chelsea and Westminster NHS in London, and colleagues reported in Clinical Microbiology and Infection. Having pre-existing cardiac disorders increased the risk for AKI by 2.4-fold — a novel finding.

Experiencing a 1.2- to 1.5-fold increase in serum creatinine within the first 2 to 4 days of therapy was significantly associated with a 3.7-fold higher risk for AKI. Similarly, an early increase in serum potassium of 0.6 mmol/L predicted a significant 2.5-fold higher risk for hyperkalemia. Higher baseline serum potassium predisposed cotrimoxazole users to hyperkalemia.

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Risks appeared dose-dependent. Low-dose cotrimoxazole (less than 1920 mg/d) was significantly associated with lower AKI and hyperkalemia risks.

“Renal function, serum potassium and pre-existing cardiac disorders should be evaluated before prescribing cotrimoxazole,” Hughes’ team advised. “Serum creatinine and potassium monitoring within first 2-4 days of treatment to identify susceptible patients is recommended, and the lowest effective dose [of cotrimoxazole] prescribed.”

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.

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Rajput J, Moore LS, Mughal N, Hughes S. Evaluating the risk of hyperkalaemia and acute kidney injury with cotrimoxazole: a retrospective observational study [published online March 24, 2020]. Clin Microbio Infect. doi: 10.1016/j.cmi.2020.02.021