Early oral switch in low-risk Staphylococcus aureus bloodstream infection

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][1] in ClinicalTrials.gov, as DRKS00004741 in the German Clinical trials register, and as EudraCT 2013-000577-77. ### Competing Interest Statement AJK received funding for this study from the Deutsche Forschungsgemeinschaft and is chairperson of the German Sepsis Society. HSe received grants or research support from the Bundesministerium fuer Bildung und Forschung (BMBF), Germany and the German Center for Infection Research (DZIF), and has been a consultant for Debiopharm, Gilead, MSD, and Shionogi. JF has received travel support by Pfizer. JRB has received grants or research support from the Spanish Network for Research in Infectious Diseases (REIPI) and CIBERINFEC, Instituto de Salud Carlos III, Spanish Ministry of Science and Innovation. JRB received research support by Plan Nacional de I+D+i 2013-2016 and Instituto de Salud Carlos III, Ministerio de Ciencia e Innovacion, Spanish Network for Research in Infectious Diseases (REIPI RD16/0016/00001) and CIBERINFEC (CB21/13/00012), co-financed by European Development Regional Fund, A way to achieve Europe, Operative Program Intelligence Growth 2014-2020. SH received honoraria and travel support from Shionogi, Pfizer, Infectopharm, and AdvanzPharma. All other authors declared no conflicting interests. ### Clinical Trial NCT01792804 DRKS00004741 ### Funding Statement This study was funded by German Research Foundation (DFG); grant number KA 3104/2-1 ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethics committee of Medizinische Fakultaet der Universitaet zu Koeln, Cologne, Germany gave ethical approval for this work. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors as detailed in the supplementary material. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT01792804&atom=%2Fmedrxiv%2Fearly%2F2023%2F07%2F05%2F2023.07.03.23291932.atom