Does Switching From Trimethoprim/Sulfamethoxazole to Atovaquone Result in Less Hyperkalemia? A Single-Center...

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.

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.

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.

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.