The objective of SNAP is to identify the effect of a range of clinical interventions on all-cause 90-day mortality in patients with SAB.
Staphylococcus aureus bacteraemia (SAB) is a common and severe infection with a 90-day mortality of 15-30% (mortality lower in children but up to 5%) despite current best available therapies. There are few high-quality data to inform the management of this infection, with less than 3000 patients randomised into any therapeutic trial for SAB prior to 2020. The current standard treatment for MSSA (methicillin-susceptible Staphylococcus aureus) and PSSA (penicillin-susceptible S. aureus) is (flu)cloxacillin monotherapy, and for MRSA (methicillin-resistant S. aureus) is vancomycin monotherapy, each given for 2-6 weeks intravenously. In-vitro, pharmacokinetic and observational data suggest that penicillin may be superior to (flu)cloxacillin for PSSA and that cefazolin may be superior to (flu)cloxacillin for MSSA. The CAMERA1 and 2 trials suggest that adding a beta-lactam to vancomycin for MRSA clears bacteraemia faster, but that the combination of vancomycin and (flu)cloxacillin is nephrotoxic. Preliminary data also suggest that clindamycin, which switches off exotoxin production by S. aureus, may improve outcomes, and that it may be possible to switch from intravenous to oral antibiotics part way through the treatment course without compromising outcomes. We are using an adaptive platform trial to allow us to simultaneously address these questions in the management of SAB. The trial will include 3 silos (PSSA, MSSA, and MRSA). We plan to test interventions within 3 initial domains (see section 2.1.1), with the potential to add further domains to the platform.

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