Antipseudomonal β-lactam dosing in sepsis with acute kidney injury: Full steam ahead

Patients with sepsis often present with acute kidney injury that typically resolves over the course of hospitalization, raising a question as to whether initial dosing of antimicrobial therapy should be adjusted to reflect decreased renal function in an otherwise hyperdynamic state. A recent study published in Open Forum Infectious Diseases provides insight with regard to outcomes when antipseudomonal β-lactams are dose-adjusted initially versus later in hospitalization.

Authors at four hospitals in Saudi Arabia observed whether adult patients with sepsis associated with acute kidney injury (defined as an increase in serum creatinine at least 1.5 fold from baseline) received, after an initial full dose of an antipseudomonal β-lactam, dose reduction to reflect decreased renal function within the first 24 hours of sepsis recognition versus dose reduction after 24 hours. Eighty-four patients were in the early dose adjustment group, and 140 were in the late dose adjustment group; 55% overall received piperacillin-tazobactam as their antipseudomonal β-lactam. Mean age of the cohort was 63 years, 62% were male, and pneumonia was the documented source of infection in 51%. Patients with end-stage renal disease or those who required renal replacement therapy during hospitalization were excluded. In a multivariable model, late adjustment was associated with a significant reduction in in-hospital mortality within 90 days (hazard ratio, 0.588; 95% confidence interval, 0.355-0.974). The late adjustment group also had a higher rate of renal recovery at 48 hours and 7 days (possibly due to lower severity of illness at baseline).

While this study is limited by its retrospective observational nature, it nonetheless underscores the importance of adequate dosing of antipseudomonal β-lactams in patients with potentially severe infections, even in the setting of acute kidney injury that is often transitory. A wise nephrologist I encountered in my training, while explaining how to correct hyponatremia, would quote the poet E.E. Cummings: “Nobody beautiful ever hurries.” Perhaps this applies to renally adjusting β-lactam therapy in the setting of sepsis as well.

(Aldardeer et al. Open Forum Infect Dis. Published online: Feb. 1, 2024.)