Does Switching From Trimethoprim/Sulfamethoxazole to Atovaquone Result in Less Hyperkalemia? A Single‐Center Retrospective Analysis in Heart Transplant Patients

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Abstract
Background: Trimethoprim/sulfamethoxazole (TMP/SMX) is commonly used after orthotopic heart transplant (OHT) for opportunistic infection (OI) prophylaxis, but its contribution to hyperkalemia is uncertain. Whether switching to atovaquone (ATQ), which has a narrower antimicrobial spectrum, affects infection risk and improves hyperkalemia has not been investigated. This study evaluated whether transitioning from TMP/SMX to ATQ in the setting of post‐OHT hyperkalemia is beneficial in lowering risk of recurrent hyperkalemia while maintaining OI prophylaxis efficacy. Methods: A single‐center retrospective review of OHT patients (January 2011–April 2022) compared those maintained on TMP/SMX with those switched to ATQ due to side effects, specifically hyperkalemia. The primary endpoint was the resolution of hyperkalemia, and the secondary endpoint was the combined infection rate. Results: Among 321 OHT recipients, 76% were switched to ATQ. Patients switched to ATQ had higher rates of severe and recurrent hyperkalemia and experienced numerically higher overall infection rates compared to TMP/SMX patients (27% vs. 52%; p < 0.001). However, in a Poisson regression model adjusted for immortal time bias, the incidence rate ratio (IRR) for infections with ATQ versus TMP/SMX was 1.32 (95% CI: 0.93–1.86; p = 0.119). Multivariable analyses excluding chronic kidney disease patients confirmed TMP/SMX's association with lower hyperkalemia rates (initial/recurrent). Age and diabetes independently predicted initial hyperkalemia. Conclusions: Transitioning from TMP/SMX to ATQ did not decrease hyperkalemia rates and was associated with a numerically higher incidence of infections, though this difference was not statistically significant. Hyperkalemia is likely multifactorial and often unresolved by switching from TMP/SMX. image

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