Staphylococcus Aureus Bacteremia Antibiotic Treatment Options

Condition(s) targeted: Staphylococcus Aureus Infection

Intervention: Trimethoprim-Sulfamethoxazole (Drug); Clindamycin (Drug); Linezolid (Drug); Flucloxacillin (Drug); Cloxacillin (Drug); Vancomycin (Drug); Daptomycin (Drug); Cefazolin (Drug)

Phase: Phase 3

Status: Recruiting

Sponsored by: University of Cologne

Official(s) and/or principal investigator(s):
Achim J Kaasch, MD, Study Chair, Affiliation: University of Cologne

Overall contact:
Achim J Kaasch, MD, Phone: +4922147832100

Increasing resistance to antibiotic agents has been recognized as a major health problem worldwide that will even aggravate due to the lack of new antimicrobial agents within the next decade [1]. This threat underscores the need to maximize clinical utility of existing antibiotics, through more rational prescription, e. g. optimizing duration of treatment. Staphylococcus aureus bloodstream infection (SAB) is a common disease with about 200,000 cases occurring annually in Europe [2]. A course of at least 14 days of intravenous antimicrobials is considered standard therapy [3-5] in "uncomplicated" SAB. This relatively long course serves to prevent SAB-related complications (such as endocarditis and vertebral osteomyelitis) that may result from hematogenous dissemination to distant sites. However, there is insufficient evidence that a full course of intravenous antibiotic therapy is always required in patients with a low risk of SAB-related complications. In a multicenter, open-label, randomized controlled trial we aim to demonstrate that an early switch from intravenous to oral antimicrobial therapy is non-inferior to a conventional 14-days course of intravenous therapy regarding efficacy and safety. An early switch from intravenous to oral therapy would provide several benefits such as earlier discharge, fewer adverse reactions associated with intravenous therapy, increased quality of life, and cost savings.

Official title: Early Oral Switch Therapy in Low-risk Staphylococcus Aureus Bloodstream Infection

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: SAB-related complications

Secondary outcome:

Length of hospital stay

Survival

Complications of intravenous therapy

Detailed description: 1. WHO. WHO Global Strategy for Containment of Antimicrobial Resistance.: World Health Organization, 2001. 2. Kern WV. Management of Staphylococcus aureus bacteremia and endocarditis: progresses and challenges. Curr Opin Infect Dis 2010;23(4):346-58. 3. Gemmell CG, Edwards DI, Fraise AP, Gould FK, Ridgway GL, Warren RE. Guidelines for the prophylaxis and treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections in the UK. J Antimicrob Chemother 2006;57(4):589-608. 4. Liu C, Bayer A, Cosgrove SE, et al. Clinical practice guidelines by the Infectious Diseases Society of America for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children. Clin Infect Dis 2011;52(3):e18-55. 5. Mermel LA, Allon M, Bouza E, et al. Clinical practice guidelines for the diagnosis and management of intravascular catheter-related infection: 2009 Update by the Infectious Diseases Society of America. Clin Infect Dis 2009;49(1):1-45.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Age at least 18 years

- Not legally incapacitated

- Written informed consent from the trial subject has been obtained

- Blood culture positive for S. aureus

- At least one negative follow-up blood culture obtained within 48-72 hours after the

start of adequate therapy

- Five to seven full days of appropriate i. v. antimicrobial therapy administered prior

to randomization. Exclusion Criteria:

- Polymicrobial bloodstream infection

- Recent history of prior S. aureus bloodstream infection

- In vitro resistance of S. aureus to all oral or all i. v. study drugs

- Contraindications for all oral or all i. v. study drugs

- Signs and symptoms of complicated SAB as judged by an ID physician, such as

deep-seated focus,septic shock, prolonged bacteremia, fever on two occasions within 48h before randomization,presence of non-removable foreign body.

- Failure to remove (within 4 days) any intravascular catheter, which is present when

first positive blood culture was drawn

- Severe liver disease

- End-stage renal disease

- Severe immunodeficiency (e. g. primary immunodeficiency disorders, neutropenia CD4+

T-cell count <200/µl in HIV-positive patients, high-dose steroid therapy, recent hematopoietic stem cell transplantation, solid organ transplant)

- "Do not resuscitate"-order or life expectancy < 3 months

- Inability to take oral drugs

- Injection drug user

- Expected low compliance with drug regimen

- Participation in other interventional trials

- Pregnant women and nursing mothers

Achim J Kaasch, MD, Phone: +4922147832100

Aachen, Aachen 52074, Germany; Recruiting
Sebastian Lemmen, Prof.Dr., Principal Investigator

Berlin, Berlin 12157, Germany; Recruiting
Keikawus Arastéh, PD Dr., Principal Investigator

Uniklinik Köln, Cologne 50935, Germany; Recruiting
Bernasch, Email: christian.bernasch@uk-koeln.de
Gerd Fätkenheuer, Prof. Dr., Principal Investigator

Frankfurt, Frankfurt/Main 60590, Germany; Recruiting
Christoph Stephan, PD Dr., Principal Investigator

Freiburg, Freiburg 79106, Germany; Recruiting
Winfried V Kern, Prof. Dr., Principal Investigator

Hannover, Hannover 30625, Germany; Recruiting
Tobias Welte, Prof. Dr., Principal Investigator

Jena, Jena 07743, Germany; Recruiting
Matthias Pletz, Prof. Dr., Principal Investigator

Krefeld, Krefeld 47805, Germany; Recruiting
Katrin Kösters, Dr., Principal Investigator

Leverkusen, Leverkusen 51375, Germany; Recruiting
Stefan Reuter, PD Dr., Principal Investigator

Lübeck, Lübeck 23562, Germany; Recruiting
Jan Rupp, Prof. Dr., Principal Investigator

Regensburg, Regensburg 93053, Germany; Recruiting
Bernd Salzberger, Prof. Dr., Principal Investigator

Ulm, Ulm 89081, Germany; Recruiting
Georg Härtner, Dr., Principal Investigator

Amsterdam, Amsterdam 1105 AZ, Netherlands; Recruiting
Jan TM van der Meer, Prof. Dr., Principal Investigator

Breda, Breda 4814 CK Breda, Netherlands; Recruiting
Jan Kluytmans, Prof. Dr., Principal Investigator

Groningen, Groningen 9700 RB, Netherlands; Recruiting
Sander van Assen, Prof. Dr., Principal Investigator

Tilburg, Tilburg 5022GC, Netherlands; Recruiting
Jan Kluytmans, Prof. Dr., Principal Investigator

Utrecht, Utrecht 3584 CX, Netherlands; Recruiting
Marc Bonten, Prof. Dr., Principal Investigator

Barcelona I, Barcelona 08036, Spain; Recruiting
Alex Soriano, Prof. Dr., Principal Investigator

Barcelona II, Barcelona 08035, Spain; Recruiting
Benito Almirante, Prof. Dr., Principal Investigator

Sevilla, Sevilla 41071, Spain; Recruiting
Jesus Rodríguez-Baño, Prof. Dr., Principal Investigator

Sevilla II, Sevilla 41071, Spain; Recruiting
José Cisneros, Prof. Dr., Principal Investigator

Nottingham, Nottingham NG7 24 H, United Kingdom; Recruiting
David Turner, Prof. Dr., Principal Investigator

Starting date: November 2013
Last updated: December 2, 2014