Combination Antibiotic Therapy for Methicillin Resistant Staphylococcus Aureus Infection

CAMERA 2 - Combination Antibiotic Therapy for Methicillin Resistant Staphylococcus Aureus Infection - An Investigator-initiated, Multi-centre, Parallel Group, Open Labelled Randomised Controlled Trial

The aim of this clinical trial is to determine whether a novel combination antibiotic treatment (vancomycin/daptomycin + beta-lactam) is superior to the standard antibiotic treatment (vancomycin/daptomycin) for hospitalised adults with Methicillin Resistant Staphylococcus aureus bacteraemia. The hypothesis is that the addition of beta-lactam antibiotics (these are antibiotics from the penicillin family) to the standard therapy will lead to more efficient bacterial killing and hence lead to faster clearance of bacteria from the blood stream and other areas of infection, thereby reducing the risk of the spread of infection and death.

The study design is an investigator-initiated, multi-centre, open-label, randomised controlled trial. This will include 440 participants diagnosed with Methicillin Resistant Staphylococcus aureus bacteraemia recruited over a period of 4 years (July 2015 - June 2019) from within Infectious Diseases inpatient units across 21 hospital sites including 18 from within Australia and 3 located in Singapore. Participation will be voluntary and subject to informed consent. The participants will be randomised 1:1 to either the standard therapy group or combination therapy group. The combination therapy will include a treatment of intravenous beta-lactam for the first 7 days of treatment, in addition to the standard treatment (either vancomycin or daptomycin). The primary outcome measure will be complication-free survival 90 days post randomisation.

Inclusion Criteria:

1. Age >= 18 years.
2. ≥1 set of blood cultures positive for MRSA
3. Able to be randomized within 72 hours of blood cultures being collected.
4. Likely to remain as inpatient for 7 days following randomization

Exclusion Criteria:

1. Previous type 1 hypersensitivity reaction to ß-lactams
2. Polymicrobial bacteraemia (not counting contaminants)
3. Previous participation in the trial
4. Known pregnancy
5. Current β-lactam antibiotic therapy which cannot be ceased or substituted
6. Participant's primary clinician unwilling to enrol patient
7. Moribund (expected to die in next 48 hours with or without treatment)
8. Treatment limitations which preclude the use of antibiotics Note that we are NOT planning to exclude participants with renal failure.