Staphylococcus aureus

Although bacterial genomic data is becoming readily generated and used for infection control and public health purposes, there has been limited uptake for direct clinical application. Staphylococcus aureus bloodstream (SAB) infections are highly prevalent in Australia with ~5,000 infections/year, require hospitalisation for treatment, can be deadly and the disease can be exacerbated by antibiotic resistance. Making S. aureus (SA) a tractable pathogen and candidate for real-time genomics in the hospital setting. Numerous studies have shown that whole-genome sequencing (WGS) and subsequent interrogation of the SA genome can reliably detect genotypes that are known to confer antibiotic resistant phenotypes. However, real-world data on the integration of genotypic resistance testing into clinical practice are lacking. Moreover, little is known on the potential clinical interest of genomic information unrelated to antibiotic resistance (determination of genetic lineage [sequence typing, clonal complex], detection of virulence genes and acquired genetic alterations such as mutations, indels and structural variation associated with antibiotic tolerance or immune evasion).

The SNAP trial is a large multi-national adaptive platform trial that aims at including thousands of patients with SAB and to test in parallel a range of antibiotic regimens. To facilitate the translation of understandings of the relationship between genomic features and treatment responses will require genomic pipelines that can provide results in a clinically actionable time frame. Here, we propose a pilot study of real-time sequencing of baseline SAB isolates within the framework of the SNAP trial (SNAP-SEQ).

Project Aims

Specific Aim: Establish a bespoke standardised genomic pipeline for clinical reporting of bacterial genomic features of S. aureus (SA) bloodstream isolates.

1. Develop a survey for infectious diseases clinicians and clinical microbiologists to engage thoughts on sequencing of SA in the clinic and to identify information useful to include in sequencing report.

2. Develop a genome sequencing report template that contains useful information for infection control/management of SA that is easy to interoperate by treating clinicians.

3. Undertake a snapshot over a 3-month period to evaluate feasibility and utility of a real-time genomic pipeline for SA in the clinical setting.

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