Questioning Non-inferiority: Methodological Concerns in the Meta-analysis of Oral vs Intravenous Therapy for Staphylococcus aureus Bacteremia

To the Editor—We read with great interest the meta-analysis by Mourad et al [1]. and the follow-up correspondence by Lee TC et al [2]. on switching intravenous (IV) therapy to oral therapy for Staphylococcus aureus bacteremia. Although the topic is clinically relevant, we have significant concerns regarding the conclusions drawn from this analysis. The meta-analysis included 4 studies, 2 of which—POET (Partial Oral vs Intravenous Antibiotic Treatment of Endocarditis) [3] and SABATO (Efficacy and Safety of an Early Oral Switch in Low-Risk Staphylococcus aureus Bloodstream Infection) [4]—are pivotal in shaping the overall interpretation. However, both studies have major limitations that challenge the sweeping conclusion of equivalence between oral and IV therapy. Staphylococcus aureus bacteremia carries a 90-day mortality of up to 27%, with frequent metastatic complications and relapse. Given these risks, the evidence presented does not justify a broad recommendation for oral therapy. Both trials involved highly selected patients and prolonged initial IV therapy, which does not reflect typical clinical scenarios. Furthermore, the widened non-inferiority margins raise serious concerns about the robustness of these findings.