TY - JOUR
T1 - Efficacy and safety of an early oral switch in low-risk Staphylococcus aureus bloodstream infection (SABATO)
T2 - an international, open-label, parallel-group, randomised, controlled, non-inferiority trial
AU - Kaasch, Achim J.
AU - López-Cortés, Luis Eduardo
AU - Rodríguez-Baño, Jesús
AU - Cisneros, José Miguel
AU - Dolores Navarro, M.
AU - Fätkenheuer, Gerd
AU - Jung, Norma
AU - Rieg, Siegbert
AU - Lepeule, Raphaël
AU - Coutte, Laetitia
AU - Bernard, Louis
AU - Lemaignen, Adrien
AU - Kösters, Katrin
AU - MacKenzie, Colin R.
AU - Soriano, Alex
AU - Hagel, Stefan
AU - Fantin, Bruno
AU - Lafaurie, Matthieu
AU - Talarmin, Jean Philippe
AU - Dinh, Aurélien
AU - Guimard, Thomas
AU - Boutoille, David
AU - Welte, Tobias
AU - Reuter, Stefan
AU - Kluytmans, Jan
AU - Martin, Maria Luisa
AU - Forestier, Emmanuel
AU - Stocker, Hartmut
AU - Vitrat, Virginie
AU - Tattevin, Pierre
AU - Rommerskirchen, Anna
AU - Noret, Marion
AU - Adams, Anne
AU - Kern, Winfried V.
AU - Hellmich, Martin
AU - Seifert, Harald
AU - Valiente, Adoración
AU - de Cueto, Marina
AU - Rodríguez, Ángel
AU - Molina, José
AU - Fischer, Julia
AU - Paul, Gregor
AU - Gallien, Sébastien
AU - Fihman, Vincent
AU - Lacasse, Marion
AU - Coustillères, Francois
AU - Becker, Christian
AU - Fuchs, André
AU - Morata, Laura
AU - Bonten, Marc J.M.
N1 - Publisher Copyright:
© 2024 Elsevier Ltd
PY - 2024/5
Y1 - 2024/5
N2 - Background: Staphylococcus aureus bloodstream infection is treated with at least 14 days of intravenous antimicrobials. We assessed the efficacy and safety of an early switch to oral therapy in patients at low risk for complications related to S aureus bloodstream infection. Methods: In this international, open-label, randomised, controlled, non-inferiority trial done in 31 tertiary care hospitals in Germany, France, the Netherlands, and Spain, adult patients with low-risk S aureus bloodstream infection were randomly assigned after 5–7 days of intravenous antimicrobial therapy to oral antimicrobial therapy or to continue intravenous standard therapy. Randomisation was done via a central web-based system, using permuted blocks of varying length, and stratified by study centre. The main exclusion criteria were signs and symptoms of complicated S aureus bloodstream infection, non-removable foreign devices, and severe comorbidity. The composite primary endpoint was the occurrence of any complication related to S aureus bloodstream infection (relapsing S aureus bloodstream infection, deep-seated infection, and mortality attributable to infection) within 90 days, assessed in the intention-to-treat population by clinical assessors who were masked to treatment assignment. Adverse events were assessed in all participants who received at least one dose of study medication (safety population). Due to slow recruitment, the scientific advisory committee decided on Jan 15, 2018, to stop the trial after 215 participants were randomly assigned (planned sample size was 430 participants) and to convert the planned interim analysis into the final analysis. The decision was taken without knowledge of outcome data, at a time when 126 participants were enrolled. The new sample size accommodated a non-inferiority margin of 10%; to claim non-inferiority, the upper bound of the 95% CI for the treatment difference (stratified by centre) had to be below 10 percentage points. The trial is closed to recruitment and is registered with ClinicalTrials.gov (NCT01792804), the German Clinical trials register (DRKS00004741), and EudraCT (2013–000577–77). Findings: Of 5063 patients with S aureus bloodstream infection assessed for eligibility, 213 were randomly assigned to switch to oral therapy (n=108) or to continue intravenous therapy (n=105). Mean age was 63·5 (SD 17·2) years and 148 (69%) participants were male and 65 (31%) were female. In the oral switch group, 14 (13%) participants met the primary endpoint versus 13 (12%) in the intravenous group, with a treatment difference of 0·7 percentage points (95% CI –7·8 to 9·1; p=0·013). In the oral switch group, 36 (34%) of 107 participants in the safety population had at least one serious adverse event compared with 27 (26%) of 103 participants in the intravenous group (p=0·29). Interpretation: Oral switch antimicrobial therapy was non-inferior to intravenous standard therapy in participants with low-risk S aureus bloodstream infection. However, 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. Funding: Deutsche Forschungsgemeinschaft. Translations: For the German, Spanish, French and Dutch translations of the abstract see Supplementary Materials section.
AB - Background: Staphylococcus aureus bloodstream infection is treated with at least 14 days of intravenous antimicrobials. We assessed the efficacy and safety of an early switch to oral therapy in patients at low risk for complications related to S aureus bloodstream infection. Methods: In this international, open-label, randomised, controlled, non-inferiority trial done in 31 tertiary care hospitals in Germany, France, the Netherlands, and Spain, adult patients with low-risk S aureus bloodstream infection were randomly assigned after 5–7 days of intravenous antimicrobial therapy to oral antimicrobial therapy or to continue intravenous standard therapy. Randomisation was done via a central web-based system, using permuted blocks of varying length, and stratified by study centre. The main exclusion criteria were signs and symptoms of complicated S aureus bloodstream infection, non-removable foreign devices, and severe comorbidity. The composite primary endpoint was the occurrence of any complication related to S aureus bloodstream infection (relapsing S aureus bloodstream infection, deep-seated infection, and mortality attributable to infection) within 90 days, assessed in the intention-to-treat population by clinical assessors who were masked to treatment assignment. Adverse events were assessed in all participants who received at least one dose of study medication (safety population). Due to slow recruitment, the scientific advisory committee decided on Jan 15, 2018, to stop the trial after 215 participants were randomly assigned (planned sample size was 430 participants) and to convert the planned interim analysis into the final analysis. The decision was taken without knowledge of outcome data, at a time when 126 participants were enrolled. The new sample size accommodated a non-inferiority margin of 10%; to claim non-inferiority, the upper bound of the 95% CI for the treatment difference (stratified by centre) had to be below 10 percentage points. The trial is closed to recruitment and is registered with ClinicalTrials.gov (NCT01792804), the German Clinical trials register (DRKS00004741), and EudraCT (2013–000577–77). Findings: Of 5063 patients with S aureus bloodstream infection assessed for eligibility, 213 were randomly assigned to switch to oral therapy (n=108) or to continue intravenous therapy (n=105). Mean age was 63·5 (SD 17·2) years and 148 (69%) participants were male and 65 (31%) were female. In the oral switch group, 14 (13%) participants met the primary endpoint versus 13 (12%) in the intravenous group, with a treatment difference of 0·7 percentage points (95% CI –7·8 to 9·1; p=0·013). In the oral switch group, 36 (34%) of 107 participants in the safety population had at least one serious adverse event compared with 27 (26%) of 103 participants in the intravenous group (p=0·29). Interpretation: Oral switch antimicrobial therapy was non-inferior to intravenous standard therapy in participants with low-risk S aureus bloodstream infection. However, 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. Funding: Deutsche Forschungsgemeinschaft. Translations: For the German, Spanish, French and Dutch translations of the abstract see Supplementary Materials section.
UR - http://www.scopus.com/inward/record.url?scp=85182783663&partnerID=8YFLogxK
U2 - 10.1016/S1473-3099(23)00756-9
DO - 10.1016/S1473-3099(23)00756-9
M3 - Article
C2 - 38244557
SN - 1473-3099
VL - 24
SP - 523
EP - 534
JO - The Lancet Infectious Diseases
JF - The Lancet Infectious Diseases
IS - 5
ER -