title: Early oral switch therapy in low-risk Staphylococcus aureus bloodstream infection (SABATO): study protocol for a randomized controlled trial.
abstract: BACKGROUND
  Current guidelines recommend that patients with Staphylococcus aureus bloodstream infection (SAB) are treated with long courses of intravenous antimicrobial therapy. This serves to avoid SAB-related complications such as relapses, local extension and distant metastatic foci. However, in certain clinical scenarios, the incidence of SAB-related complications is low. Patients with a low-risk for complications may thus benefit from an early switch to oral medication through earlier discharge and fewer complications of intravenous therapy. The major objective for the SABATO trial is to demonstrate that in patients with low-risk SAB a switch from intravenous to oral antimicrobial therapy (oral switch therapy, OST) is non-inferior to a conventional course of intravenous therapy (intravenous standard therapy, IST).
  
  
  METHODS
  The trial is designed as randomized, parallel-group, observer-blinded, clinical non-inferiority trial. The primary endpoint is the occurrence of a SAB-related complication (relapsing SAB, deep-seated infection, and attributable mortality) within 90 days. Secondary endpoints are the length of hospital stay; 14-day, 30-day, and 90-day mortality; and complications of intravenous therapy. Patients with SAB who have received 5 to 7 full days of adequate intravenous antimicrobial therapy are eligible. Main exclusion criteria are polymicrobial bloodstream infection, signs and symptoms of complicated SAB (deep-seated infection, hematogenous dissemination, septic shock, and prolonged bacteremia), the presence of a non-removable foreign body, and severe comorbidity. Patients will receive either OST or IST with a protocol-approved antimicrobial and are followed up for 90 days. Four hundred thirty patients will be randomized 1:1 in two study arms. Efficacy regarding incidence of SAB-related complications is tested sequentially with a non-inferiority margin of 10 and 5 percentage points.
  
  
  CONCLUSIONS
  The SABATO trial assesses whether early oral switch therapy is safe and effective for patients with low-risk SAB. Regardless of the result, this pragmatic trial will strongly influence the standard of care in SAB.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT01792804 registered 13 February 2013; German Clinical trials register DRKS00004741 registered 4 October 2013, EudraCT 2013-000577-77 . First patient randomized on 20 December 2013.
authors.affiliation: Institute for Medical Microbiology, Immunology and Hygiene, University of Cologne, Goldenfelsstr. 19-21, D-50935, Köln, Germany. achim.kaasch@uk-koeln.de.
authors.forename: Achim J
authors.initials: AJ
authors.lastname: Kaasch
authors.affiliation: Department I of Internal Medicine, University Hospital of Cologne, 50924, Cologne, Germany. g.faetkenheuer@uni-koeln.de.|German Centre for Infection Research (DZIF), partner site Bonn-Cologne, Germany. g.faetkenheuer@uni-koeln.de.
authors.forename: Gerd
authors.initials: G
authors.lastname: Fätkenheuer
authors.affiliation: Clinical Trial Center Cologne, University of Cologne, 50924, Cologne, Germany. reinhild.prinz-langenohl@uk-koeln.de.
authors.forename: Reinhild
authors.initials: R
authors.lastname: Prinz-Langenohl
authors.affiliation: Clinical Trial Center Cologne, University of Cologne, 50924, Cologne, Germany. ursula.paulus@uk-koeln.de.
authors.forename: Ursula
authors.initials: U
authors.lastname: Paulus
authors.affiliation: Institute of Medical Statistics, Informatics and Epidemiology, University of Cologne, Kerpener Straße 62, 50924, Cologne, Germany. martin.hellmich@uni-koeln.de.
authors.forename: Martin
authors.initials: M
authors.lastname: Hellmich
authors.affiliation: Institute of Medical Statistics, Informatics and Epidemiology, University of Cologne, Kerpener Straße 62, 50924, Cologne, Germany. verena.weiss@uni-koeln.de.
authors.forename: Verena
authors.initials: V
authors.lastname: Weiß
authors.affiliation: Department I of Internal Medicine, University Hospital of Cologne, 50924, Cologne, Germany. norma.jung@uk-koeln.de.
authors.forename: Norma
authors.initials: N
authors.lastname: Jung
authors.affiliation: Department of Medicine, Center for Infectious Diseases and Travel Medicine, University Medical Center Freiburg, Hugstetter Straße 55, 79106, Freiburg, Germany. siegbert.rieg@uniklinik-freiburg.de.
authors.forename: Siegbert
authors.initials: S
authors.lastname: Rieg
authors.affiliation: Department of Medicine, Center for Infectious Diseases and Travel Medicine, University Medical Center Freiburg, Hugstetter Straße 55, 79106, Freiburg, Germany. winfried.kern@uniklinik-freiburg.de.
authors.forename: Winfried V
authors.initials: WV
authors.lastname: Kern
authors.affiliation: Institute for Medical Microbiology, Immunology and Hygiene, University of Cologne, Goldenfelsstr. 19-21, D-50935, Köln, Germany. harald.seifert@uni-koeln.de.|German Centre for Infection Research (DZIF), partner site Bonn-Cologne, Germany. harald.seifert@uni-koeln.de.
authors.forename: Harald
authors.initials: H
authors.lastname: Seifert
mesh_terms: D061605:Administration, Intravenous; D000284:Administration, Oral; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000009:adverse effects; D016470:Bacteremia / Q000175:diagnosis / Q000188:drug therapy* / Q000382:microbiology / Q000401:mortality; D002985:Clinical Protocols; D018450:Disease Progression; D005060:Europe; D006801:Humans; D012008:Recurrence; D012107:Research Design; D012307:Risk Factors; D013203:Staphylococcal Infections / Q000175:diagnosis / Q000188:drug therapy* / Q000382:microbiology / Q000401:mortality; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000302:isolation & purification; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents