Status:
COMPLETED
Staphylococcus Aureus Bacteremia Antibiotic Treatment Options
Lead Sponsor:
Heinrich-Heine University, Duesseldorf
Collaborating Sponsors:
German Research Foundation
Conditions:
Staphylococcus Aureus Infection
Eligibility:
All Genders
18+ years
Phase:
PHASE3
Brief Summary
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 \[1\]. Th...
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 c...
Eligibility Criteria
Inclusion
- Age at least 18 years
- Not legally incapacitated
- Written informed consent from the trial subject has been obtained
- Blood culture positive for S. aureus not considered to represent contamination
- At least one negative follow-up blood culture obtained within 24-96 hours after the start of adequate antimicrobial therapy to rule out persistent bacteremia and Absence of a blood culture positive for S. aureus at the same time or thereafter.
- Five to seven full days of appropriate i.v. antimicrobial therapy administered prior to randomization documented in the patient Chart. Appropriate therapy has all of the following characteristics:
- Antimicrobial therapy has to be initiated within 72h after the first positive blood culture was drawn.
- Provided in-vitro susceptibility and adequate dosing (as judged by the PI) preferred agents for pre-randomization antimicrobial therapy are flucloxacillin, cloxacillin, vancomycin and daptomycin. However, the following antimicrobials are allowed:
- MSSR: penicillinase-resistant penicillins (e.g. flucloxacillin, cloxacillin), β-lactam plus β-lactamase-inhibitors (e.g. ampicillin+sulbactam, piperacillin+tazobactam), cephalosporins (except ceftazidime), carbapenems, clindamycin, fluoroquinolones, trimethoprimsulfamethoxazole, doxycycline, tigecycline, vancomycin, teicoplanin, telavancin, linezolid, daptomycin, ceftaroline, ceftobiprole, and macrolides.
- MRSA: vancomycin, teicoplanin, telavancin, fluoroquinolones, clindamycin, trimethoprim-sulfamethoxazole, doxycycline, tigecycline, linezolid, daptomycin, macrolides, ceftaroline, and ceftobiprole.
Exclusion
- Polymicrobial bloodstream infection, defined as isolation of pathogens other than S. aureus from a blood culture obtained in the time from two days prior to the first positive blood culture with S. aureus until randomization. Common skin contaminants (coagulase-negative staphylococci, diphtheroids, Bacillus spp., and Propionibacterium spp.) detected in one of several blood cultures will not be considered to represent polymicrobial infection
- Recent history (within 3 months) 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
- Previously planned Treatment with active drug against S. aureus during Intervention Phase (e.g. cotrimoxazol prophylaxis)
- Signs and symptoms of complicated SAB as judged by an ID physician. Complicated infection is defined as at least one of the following:
- deep-seated focus: e.g. endocarditis, pneumonia, undrained abscess, empyema, and Osteomyelitis
- septic shock, as defined by the AACP criteria (23), within 4 days before randomization
- prolonged bacteremia: positive follow-up blood culture more than 72h after the start of adequate antimicrobial therapy
- body temperature \>38 °C on two separate days within 48h before randomization
- Presence of the following non-removable foreign bodies (if not removed 2 days or more before randomization):
- prosthetic heart valve
- deep-seated vascular graft with foreign material (e.g. PTFE or dacron graft). Hemodialysis shunts are not considered deep-seated vascular grafts.
- ventriculo-atrial shunt
- Presence of a prosthetic joint (if not removed 2 days or more before randomization). This is not an exclusion criterion, if all of the following conditions are fulfilled:
- prosthetic joint was implanted at least 6 months prior, and
- catheter-related infection, skin and soft tissue infection, or surgical wound infection is present (as defined below), and
- joint infection unlikely (no clinical or imaging signs)
- Presence of a pacemaker or an automated implantable cardioverter Defibrillator (AICD) device (if not removed 2 days or more before randomization). This is not an exclusion criterion, if all of the following conditions are fulfilled:
- pacemaker or AICD was implanted at least 6 months prior, and
- catheter-related infection, skin and soft tissue infection, or surgical wound infection is present (as defined below), and
- no clinical signs of infective endocarditis, and
- infective endocarditis unlikely by echocardiography (preferably TEE), and
- pocket infection unlikely (no clinical or imaging signs)
- Failure to remove any intravascular catheter which was present when first positive blood culture was drawn within 4 days of the first positive blood culture
- Severe liver disease. This is not an exclusion criterion, if the following condition is fulfilled:
- \- catheter-related infection, skin and soft tissue infection, or surgical wound infection is present
- End-stage renal disease. This is not an exclusion criterion, if all of the following conditions are fulfilled:
- catheter-related infection, skin and soft tissue infection, or surgical wound infection is present (as defined below), and
- no clinical signs of infective endocarditis, and
- infective endocarditis unlikely by echocardiography (preferably TEE), and
- in patients with a hemodialysis shunt with a non-removable foreign body (e.g. synthetic PTFE loop): no clinical signs of a shunt infection
- Severe immunodeficiency
- primary immunodeficiency disorders
- neutropenia (\<500 neutrophils/μl) at randomization or neutropenia expected during intervention phase due to immunosuppressive treatment
- uncontrolled disease in HIV-positive patients
- high-dose steroid therapy (\>1 mg/kg prednisone or equivalent doses given for \>4 weeks or planned during intervention)
- immunosuppressive combination therapy with two or more drugs with different mode of action
- hematopoietic stem cell transplantation within the past 6 months or planned during treatment period
- solid organ transplant
- treatment with biologicals within the previous year
- Life expectancy \< 3 months
- Inability to take oral drugs
- Injection drug user
- Expected low compliance with drug regimen
- Participation in other interventional trials within the previous three months or ongoing
- Pregnant women and nursing mothers
- For premenopausal women: Failure to use highly-effective contraceptive methods for 1 month after receiving study drug. The following contraceptive methods with a Pearl Index lower than 1% are regarded as highly-effective:
- oral hormonal contraception ('pill')
- dermal hormonal contraception
- vaginal hormonal contraception (NuvaRing®)
- contraceptive plaster
- long-acting injectable contraceptives
- implants that release progesterone (Implanon®)
- tubal ligation (female sterilisation)
- intrauterine devices that release hormones (hormone spiral)
- double barrier methods
- Persons with any kind of dependency on the investigator or employed by the sponsor or investigator
- Persons held in an institution by legal or official order
Key Trial Info
Start Date :
December 1 2013
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
March 26 2020
Estimated Enrollment :
215 Patients enrolled
Trial Details
Trial ID
NCT01792804
Start Date
December 1 2013
End Date
March 26 2020
Last Update
May 27 2020
Active Locations (40)
Enter a location and click search to find clinical trials sorted by distance.
1
Annecy
Annecy, France, 74000
2
Chambéry
Chambéry, France, 73000
3
Grenoble
Grenoble, France, 38700
4
La Roche-sur-Yon
La Roche-sur-Yon, France, 85000