Efficacy and safety of an early oral switch in low-risk Staphylococcus aureus bloodstream infection (SABATO): an international, open-label, parallel-group, randomised, controlled, non-inferiority trial
In RCT (n=213), switching to oral antimicrobial therapy (AMT) after 5-7 days of IV standard therapy (ST), with total duration of AMT of 14 days, was non-inferior to continuing IV ST (13% met primary endpoint vs 12%, respectively, difference 0.7%; 95% CI –7.8 to 9.1; p=0.013).
Source:
The Lancet Infectious Diseases
SPS commentary:
In the study, the composite primary endpoint was the occurrence of any complication related to S aureus bloodstream (SAB) infection (relapsing S aureus bloodstream infection, deep-seated infection, and mortality attributable to infection) within 90 days, assessed in the intention-to-treat population. For non-inferiority, the upper bound of 95% CI for treatment difference had to be <10%. The researchers point out it is necessary to carefully assess patients for signs and symptoms of complicated S aureus bloodstream infection at the time of presentation and thereafter before considering early oral switch therapy.
According to a commentary, despite the immense and laudable effort to enrol across 31 sites over 6 years, the recruitment rate was low at 4.2% (213 of 5063), which ultimately resulted in the termination of trial enrolment at just half of the original target population. It notes that with this decrease in power, the original non-inferiority margin of 5% was liberalised to 10% for the primary analyses, and when coupled with infrequent event rates, limits the ability of study to definitively address the study question at hand. It adds that this highlights the known challenge of studying low-risk (uncomplicated) SAB infection. It commends the authors for their efforts and commitment to this important clinical question, and with the challenges faced during this trial, suggests strategy researching SAB should be adjusted to evaluate oral switch therapy for all forms of SAB, include more objective primary endpoints, and minimise the risk of poor outcome by focusing on the optimised oral regimens most likely to succeed on the basis of pharmacokinetic and pharmacodynamic principles. It concludes that whilst definitive data are awaited, the results of this trial, when combined with OLIVIA and POET, should continue to dispel the long-held dogma that IV antibiotics are better simply because they are given by that route.