Same-day confirmation of infection and antimicrobial susceptibility profiling using flow cytometry.

BACKGROUND

The annual mortality burden of antimicrobial resistant infections exceeds 1.27 million/year. With serious infections, every hour without effective antimicrobial therapy results in a 6.7% increased risk of death. New technology that delivers actionable pathology results in clinically-relevant timeframes is an urgent priority. We present the development and validation of an acoustic-enhanced flow cytometric (AFC) workflow that provides same-day confirmation of infection and antimicrobial susceptibility, using peritoneal dialysis (PD)-associated peritonitis as a demonstrative example.

METHODS

In this cohort study, we analysed peritoneal dialysis effluent specimens using AFC to confirm the presence of infection and antimicrobial susceptibility of identified organisms. The primary outcome was the performance of the assay compared to conventional microbiology performed by the clinical laboratory. A secondary outcome was time to result.

FINDINGS

AFC confirmed infection from primary specimens (n=116), with a sensitivity of 86% and specificity of 94% in ≤ one hour from arrival, including confirmation of infecting organisms in culture-negative cases. Combined with flow-cytometry-assisted antimicrobial susceptibility testing (FAST), we demonstrate same-day antimicrobial susceptibility profiles with an accuracy equivalent to conventional laboratory-based tests.

INTERPRETATION

Application of AFC based assays to confirm infection and predict antimicrobial susceptibility can deliver actionable results with a performance that meets or exceeds currently utilised microbiological tests in clinically meaningful timeframes, as demonstrated for PD peritonitis. This technology shows potential for broad applicability to other time-critical serious infections.

FUNDING

Government of Western Australia (Department of Health), Government of Australia (National Health and Medical Research Council) and the Forrest Research Foundation.