Early oral switch in low-riskStaphylococcus aureusbloodstream 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.

Oral Antibiotics for Bacteremia and Infective Endocarditis: Current Evidence and Future Perspectives

“…TMP/SMX, even in a dose of 320 mg/1600 mg bid, should not be used as monotherapy during the initial, IV part of treatment for bacteremia patients because it failed to meet non-inferiority criteria versus vancomycin, thus increasing treatment failure risk [68,69]. However, it can be used as oral step-down therapy according to all the aforementioned retrospective data, UK guidelines, as well as the results of the long awaited SABATO trial, where oral TMP/SMX 160/800 mg bid was used in 58.3% of the cases; another 32.4% of the participants received oral clindamycin 600 mg tid [68,70]. In this study, patients with low-risk S. aureus bacteremia were randomized to either an oral antimicrobial or to continue with IV therapy after 5-7 days of parenteral antimicrobial treatment; non-inferiority criteria for the composite primary endpoint (90-day relapse, evolution of deep-seated infection or mortality attributable to primary infection) were met [70].…”

“…However, it can be used as oral step-down therapy according to all the aforementioned retrospective data, UK guidelines, as well as the results of the long awaited SABATO trial, where oral TMP/SMX 160/800 mg bid was used in 58.3% of the cases; another 32.4% of the participants received oral clindamycin 600 mg tid [68,70]. In this study, patients with low-risk S. aureus bacteremia were randomized to either an oral antimicrobial or to continue with IV therapy after 5-7 days of parenteral antimicrobial treatment; non-inferiority criteria for the composite primary endpoint (90-day relapse, evolution of deep-seated infection or mortality attributable to primary infection) were met [70]. These data enriched the available evidence about oral treatment in bacteremia for clinically improved patients without prolonged bacteremia, concomitant pneumonia or other deep-seated infectious focus; subjects in the oral switch group hospitalized for 3.1 days less, too [70].…”

“…In this study, patients with low-risk S. aureus bacteremia were randomized to either an oral antimicrobial or to continue with IV therapy after 5-7 days of parenteral antimicrobial treatment; non-inferiority criteria for the composite primary endpoint (90-day relapse, evolution of deep-seated infection or mortality attributable to primary infection) were met [70]. These data enriched the available evidence about oral treatment in bacteremia for clinically improved patients without prolonged bacteremia, concomitant pneumonia or other deep-seated infectious focus; subjects in the oral switch group hospitalized for 3.1 days less, too [70].…”