TheStaphylococcus aureusNetwork Adaptive Platform Trial Protocol: New Tools for an Old Foe

Abstract

Staphylococcus aureus bloodstream (SAB) infection is a common and severe infectious disease, with a 90-day mortality of 15-30%. Despite this, fewer than 3000 people have been randomised into clinical trials of treatments for SAB infection. The limited evidence base partly results from clinical trials for SAB infections being difficult to complete at scale using traditional clinical trial methods. Here we provide the rationale and framework for an adaptive platform trial applied to SAB infections. We detail the design features of the Staphylococcus aureus Network Adaptive Platform (SNAP) trial that will enable multiple questions to be answered as efficiently as possible. The SNAP trial will commence enrolling patients across multiple countries in 2022 with an estimated target sample size of 7000 participants. This approach may serve as an exemplar to increase efficiency of clinical trials for other infectious diseases syndromes.

Acute bacterial lymphadenitis in children: a retrospective, cross-sectional study

“…Resistance rates of Group A Streptococci to clindamycin vary widely from 4 to 40% [17] and are on the increase [23]; hence, this agent is rarely used as monotherapy without knowledge of local antibiograms. The use of clindamycin alongside an anti-Staphylococcal backbone agent for complex S. aureus infections with associated bacteraemia has been evaluated via a pilot multi-centred randomised controlled trial in adults and children [24] and has been incorporated as a key arm of an ongoing adaptive platform trial (S. aureus Network Adaptive Platform (SNAP) trial) [25]. Its role in invasive Group A Streptococcal infection is well established in children [26] and has been shown to reduce mortality in adult cohorts when used alongside beta-lactams [27,28].…”

Diagnostic MALDI-TOF MS can differentiate between high and low toxic Staphylococcus aureus bacteraemia isolates as a predictor of patient outcome

“…Indeed, it has become standard clinical practice to add one of these antibiotics as adjuvant therapy in a range of clinical conditions including toxic shock syndrome, necrotizing fasciitis and PVL necrotizing pneumonia [13][14][15][16]. While the clinical benefit of this remains an area of some uncertainty, with limited clinical data in severe infections, clinical trials of toxin supressing adjuvant therapy in SAB are underway [23]. Given the proportion of SAB that are caused by Agr-defective, non-toxigenic S. aureus isolates, this could mask the benefit these therapies may have for highly toxic cases, as to date we have not been able to determine an isolate's toxicity in a clinically relevant timescale.…”

Clinical Impact of Staphylococcus aureus Skin and Soft Tissue Infections

“…However, ceftaroline (along with other β-lactams) may have a niche role as an adjunctive treatment for persistent MRSA bacteremia [ 221 , 222 , 223 , 224 ]. Future clinical trial platforms may provide definitive answers on the utility of adjunctive β-lactam therapy for persistent MRSA bacteremia [ 225 ].…”