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Review 1: "Early Oral Switch in Low-risk Staphylococcus Aureus Bloodstream Infection"

The reviewer believes the evidence is strong and the methodology and control group is appropriate. They had minor feedback regarding the diction in the participants section.

Published onJun 28, 2024
Review 1: "Early Oral Switch in Low-risk Staphylococcus Aureus Bloodstream Infection"
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key-enterThis Pub is a Review of
Early oral switch in low-risk Staphylococcus aureus bloodstream infection
Early oral switch in low-risk Staphylococcus aureus bloodstream infection

Abstract Background Staphylococcus aureus bloodstream infection (SAB) is treated with at least 14 days of intravenously administered antimicrobials. We assessed the efficacy and safety of an early oral switch therapy in patients at low risk for SAB-related complications.Methods In an international non-inferiority trial, we randomized patients with SAB after 5 to 7 days of intravenous antimicrobial therapy to either switch to an oral antimicrobial or to continue with intravenous standard therapy. Main exclusion criteria were signs and symptoms of complicated SAB, non-removable foreign devices, and severe comorbidity. Composite primary endpoint was the occurrence of any SAB-related complication (relapsing SAB, deep-seated infection, and mortality attributable to SAB) within 90 days.Results 213 patients were randomized into the intention-to-treat population. In the oral switch group, 14/108 (13%) participants reached the primary endpoint versus 13/105 (12%) in the standard therapy group (adjusted difference 0.7%, 95% confidence interval [CI] -7.8% to 9.1%). Participants in the oral switch group were discharged earlier (median hospital stay from SAB onset of 12 days versus 16 days; adjusted difference -3.1 days [95% CI -7.5 to 1.4]). There was no statistical difference in 30-day survival and complications of intravenous administration. More participants in the oral group experienced at least one serious adverse event (34% versus 26%, p=0.292).Conclusion Oral switch was non-inferior to intravenous standard therapy in participants with low-risk SAB. However, a careful assessment of patients for signs and symptoms of complicated SAB at time of presentation and thereafter is necessary before considering early oral switch therapy.The trial was registered as NCT01792804 in, as DRKS00004741 in the German Clinical trials register, and as EudraCT 2013-000577-77.

RR:C19 Evidence Scale rating by reviewer:

  • Strong. The main study claims are very well-justified by the data and analytic methods used. There is little room for doubt that the study produced has very similar results and conclusions as compared with the hypothetical ideal study. The study’s main claims should be considered conclusive and actionable without reservation.


Review: The main claim of this manuscript is that oral switch after 5-7 days is non-inferior to standard intravenous treatment for non-complicated Staphylococcus aureus bacteremia.

This trial is well performed and concerns a clinically relevant issue namely the length of intravenous treatment for S. aureus bacteremia (SAB). The study population is well framed and the authors discuss the problems to define uncomplicated SAB and use a pragmatic definition. The intervention is performed with reasonable drugs and dosages. The control is relevant. The outcome is chosen as a composite one composed of deep seated infection, relapse and attributable mortality.

The manuscript is very well written and I have no objections neither to the text nor to the content. In the Participants section, it is mentioned that persons were eligible for inclusion if "follow-up blood cultures obtained within 24-96 hours after the start of appropriate antimicrobial therapy were persistently negative" and then as an exclusion criterion "prolonged bacteremia (defined as a positive blood culture obtained more than 72 hours after start". This would be easier to understand if the word "persistently" was deleted from the inclusion part.

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