Staphylococcus Aureus Bacteremia Antibiotic Treatment Options - Full Text View

Purpose

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.

Condition	Intervention	Phase
Staphylococcus Aureus Bloodstream Infection	Drug: Trimethoprim-Sulfamethoxazole Drug: Clindamycin Drug: Linezolid Drug: Flucloxacillin Drug: Cloxacillin Drug: Vancomycin Drug: Daptomycin Drug: Cefazolin	Phase 3

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Early Oral Switch Therapy in Low-risk Staphylococcus Aureus Bloodstream Infection

Resource links provided by NLM:

MedlinePlus related topics: Antibiotics

Drug Information available for: Sulfamethoxazole Trimethoprim Vancomycin Vancomycin hydrochloride Clindamycin hydrochloride Clindamycin phosphate Clindamycin palmitate hydrochloride Cefazolin Cefazolin sodium Clindamycin palmitate Trimethoprim hydrochloride Staphylococcus aureus Daptomycin Linezolid

U.S. FDA Resources

Further study details as provided by University of Cologne:

Primary Outcome Measures:

SAB-related complications [ Time Frame: 90 days ] [ Designated as safety issue: No ]
S. aureus bloodstream infection-related complications (relapsing SAB, deep-seated infection with S. aureus, or attributable mortality) within 90 days

Secondary Outcome Measures:

Length of hospital stay [ Time Frame: 90 days ] [ Designated as safety issue: No ]
Length of hospital stay
Survival [ Time Frame: 14, 30, and 90 days ] [ Designated as safety issue: No ]
Survival at 14, 30, and 90 days
Complications of intravenous therapy [ Time Frame: 90 days ] [ Designated as safety issue: No ]
Complications of intravenous therapy, such as thrombophlebitis.

Other Outcome Measures:

Clostridium difficile associated diarrhea (CDAD) [ Time Frame: 90 days ] [ Designated as safety issue: Yes ]
Clostridium difficile associated diarrhea (CDAD)
AEs and SAEs [ Time Frame: 90 days ] [ Designated as safety issue: Yes ]
Adverse events

Estimated Enrollment:	430
Study Start Date:	July 2013
Estimated Study Completion Date:	September 2016
Estimated Primary Completion Date:	September 2016 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Orally administered antibiotic First choice (MRSA and MSSA): trimethoprim-sulfamethoxazole, or Second choice (MSSA): clindamycin, or Second choice (MRSA): linezolid ) administered for 7-9 days	Drug: Trimethoprim-Sulfamethoxazole Drug: Clindamycin Drug: Linezolid
Experimental: Intravenously administered antibiotic First choice (MSSA): flucloxacillin [Spain: cloxacillin], or cefazolin or Second choice (MSSA): vancomycin, or First choice (MRSA): vancomycin, or Second choice (MRSA): daptomycin) administered for 7-9 days	Drug: Flucloxacillin Drug: Cloxacillin Drug: Vancomycin Drug: Daptomycin Drug: Cefazolin

Detailed Description:

WHO. WHO Global Strategy for Containment of Antimicrobial Resistance.: World Health Organization, 2001.
Kern WV. Management of Staphylococcus aureus bacteremia and endocarditis: progresses and challenges. Curr Opin Infect Dis 2010;23(4):346-58.
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.
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.
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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01792804

Contacts

Contact: Achim J Kaasch, MD	+4922147832100
Contact: Christian M Bernasch

Locations

Germany
Uniklinik Köln	Not yet recruiting
Cologne, Germany, 50935
Principal Investigator: Gerd Fätkenheuer, Prof. Dr.

Sponsors and Collaborators

University of Cologne

German Research Foundation

Investigators

Study Chair:

Achim J Kaasch, MD

University of Cologne

More Information

No publications provided

Responsible Party:	Gerd Fätkenheuer, Prof. Dr. med., University of Cologne
ClinicalTrials.gov Identifier:	NCT01792804 History of Changes
Other Study ID Numbers:	Uni-Koeln-1400, 2013-000577-77
Study First Received:	February 13, 2013
Last Updated:	May 14, 2013
Health Authority:	Germany: Federal Institute for Drugs and Medical Devices Spain: Agencia Española de Medicamentos y Productos Sanitarios Netherlands: Medicines Evaluation Board (MEB) Switzerland: Swissmedic United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by University of Cologne:

Staphylococcus aureus
Bloodstream infection
Oral switch

Additional relevant MeSH terms:

Staphylococcal Infections
Gram-Positive Bacterial Infections
Bacterial Infections
Anti-Bacterial Agents
Cefazolin
Clindamycin
Clindamycin-2-phosphate
Cloxacillin
Floxacillin
Vancomycin
Daptomycin
Linezolid
Sulfamethoxazole
Trimethoprim

Trimethoprim-Sulfamethoxazole Combination
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Protein Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Infective Agents, Urinary
Renal Agents
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents
Folic Acid Antagonists

ClinicalTrials.gov processed this record on June 18, 2013

Staphylococcus Aureus Bacteremia Antibiotic Treatment Options (SABATO)