The objective of this nested trial is to directly compare daptomycin to vancomycin as the backbone therapy for eligible MRSA-B.
MRSA infections result in higher crude mortality than MSSA infections. The current standard therapy in many centres for MRSA-B is vancomycin. Compared with β-lactams, vancomycin kills MSSA more slowly, has less penetration of infected tissue, and in observational studies is associated with poorer patient outcomes. Alternative agents to vancomycin have become available, including daptomycin. However, daptomycin has not been demonstrated to be superior to vancomycin for MRSA-B.
Hypothesis: Within the directly randomised comparison, daptomycin will have a superior probability of attaining a higher DOOR outcome at day 90 in adults.
Sample size: 300 participants
Lead Investigator: Prof. Todd C. Lee - McGill University, Montreal, Canada
Vancomycin has been the standard of care for MRSAbacteremia for decades but it has several disadvantages including the risk of acute kidney injury and challenging pharmacology requiring therapeutic drug monitoring and dose adjustments using specialized software and/or expert pharmacy support. An important comparative effectiveness question therefore arises: can we replace vancomycin with another agent to overcome vancomycin's shortcomings? Daptomycin offers several potential advantages with less risk of acute renal failure, no requirement for therapeutic drug monitoring, and it can be given as a single dose per day (vs up to 4/day for vancomycin) requiring less nursing and pharmacy time.
Daptomycin (now generic in many countries) remaine more expensive than vancomycin (excluding administration and monitoring costs), and its use remains infrequent since daptomycin has not been demonstrated to be superior. There have been only 99 patients in RCTs directly comparing these two drugs in MRSA bacteremia. Other observational comparisons are favorable, but they are subject to confounding and immortal time bias. For most centres in SNAP, the choice of daptomycin or vancomycin is left up to the treating team. At participating hospitals, we will nest a head-to-head randomized comparison between these two drugs to provide additional comparative effectiveness data in MRSA bacteremia.
All patients eligible for the Core Platform and MRSA Backbone Domain are eligible for this substudy.
Study-specific exclusion criteria:
1) Severe allergy or non-severe rash to vancomycin OR daptomycin
2) Suspected or confirmed MRSA pneumonia
3) Known vancomycin MIC >=2mg/L or daptomycin >=1mg/L
Patients will be randomized to one of the following:
1) IV Vancomycin
2) IV Daptomycin
To be initiated as soon as possible. If already receiving either of these interventions, the timing of the next dose should be at the recommended interval from the last dose.
Duration of either intervention should be guided by local guidelines and practice for MRSA SAB.
Lead Investigator: Dr. Todd Lee
Email: todd.lee@mcgill.ca
C-SNAP: Evaluating the prevalence of vitamin C deficiency and plasma vitamin C level decay in a prospective sample of patients with Staphylococcus aureus bacteraemia enrolled in the SNAP trial
Cefazolin Versus Penicillin for Penicillin-Susceptible Staphylococcus aureus Bacteremia: A Secondary Analysis of the SNAP Backbone Trials
Combination Cefazolin with Ertapenem for methicillin-susceptible Staphylococcus aureus bacteremia.
A Versatile Analyte to Monitor Complications and Guide Treatment Duration in Staphylococcus aureus Bacteremia
SNAPstrat: Patient stratification using SAB sub-phenotypes
