Clinical Effect of Expedited Pathogen Identification and Susceptibility Testing for Gram-Negative Bacteremia and Candidemia by Use of the Accelerate PhenoTM System

Abstract

Background Fast diagnostic tests providing earlier identification (ID) of pathogens, and antimicrobial susceptibility testing (AST) may reduce time to appropriate antimicrobial therapy (AAT), decrease mortality, and facilitate antimicrobial deescalation (ADE). Our objective was to determine the theoretical reduction in time to AAT and opportunities for ADE with Accelerate PhenoTM System (AXDX). Methods The prospective cohort (April 14, 2016 through June 1, 2017) was from the Barnes-Jewish Hospital, a 1250-bed academic center. Emergency department (ED) or intensive care unit (ICU) blood cultures Gram-stain positive for gram-negative bacilli (GNB) or yeast. AXDX was used in parallel with standard-of-care (SOC) diagnostics to determine differences in time to pathogen ID and AST. Theoretical opportunities for ADE from AXDX results were determined. Results In total, 429 blood cultures were screened, 153 meeting inclusion criteria: 110 on-panel GNB, 10 Candida glabrata, and 5 Candida albicans. For GNB SOC, median time from blood culture positivity to ID and AST were 28.2 and 52.1 h. Median time to ID and AST after AXDX initiation was 1.37 and 6.7 h for on-panel organisms. For on-panel Candida, time to ID was approximately 21 h faster with AXDX. ADE or AAT was theoretically possible with AXDX in 48.4%. Of on-panel organisms, 24.0% did not receive initial AAT. In-hospital mortality was 46.7% without initial AAT, and 11.6% with AAT. Coverage of AXDX was 75.3%, specificity 99.7%, positive predictive value (PPV) 96.0%, and negative predictive value (NPV) 97.6%. On-panel sensitivity was 91.5%, specificity 99.6%, PPV 96.0%, and NPV 99.0%. Conclusions AXDX provides more rapid ID and AST for GNB and ID for yeast than SOC. AXDX could potentially reduce time to AAT and facilitate ADE.

Novel Approaches to Hasten Detection of Pathogens and Antimicrobial Resistance in the Intensive Care Unit

“…72 In a study of the Accelerate Pheno System at our institution, 153 blood cultures meeting inclusion criteria from the emergency department and ICUs were evaluated; 110 on-panel GNB, 10 Candida glabrata, 5 Candida albicans. 73 Using standard-of-care microbiology techniques for GNB, median time from blood culture positivity to ID and AST were 28.2 and 52.1 hours, respectively. Median time to ID and AST for the Accelerate Pheno System was 1.37 and 6.7 hours for on-panel organisms.…”

“…These findings are similar to those found at our institution employing similar diagnostic approaches. 73 A recent post-hoc analysis of a prospective, multicenter cohort study of patients with bloodstream infection caused by Enterobacteriaceae initially treated with ertapenem or anti-pseudomonal β-lactams sheds more light on the overall safety of ADE and the potential future role of RDTs. 103 Among Fig.…”

“…Alternatively, new technologies that provide rapid ID and AST including a rapid phenotypic antibiogram with minimum inhibitory concentration values could further enhance the ability of ICU clinicians to deescalate therapy, as well as ensure that effective treatment is prescribed at an early point in care. 73…”

Diagnostic Mycology: Xtreme Challenges

“…Diagnostic assays that combine the two are obviously complicated, although progress is being made for bacterial diagnosis. For examples, Accelerate Diagnostics, Inc. (Tucson, AZ) has a commercially available assay that utilizes a fluorescent in situ hybridization (FISH) component for identification and time lapse microscopy to measure susceptibility, all of which can be completed in ϳ5 h (33). The assay works on a variety of bacteria (identification and susceptibility) as well as two species of Candida (identification only).…”

Molecular Methods for the Diagnosis of Invasive Candidiasis

“…However, rapid susceptibility testing is not available for fungi. The test was recently evaluated in a study by Burnham et al [ 44 ]; 10 of the 125 blood cultures positive for pathogens included in the test’s panel contained C. glabrata , and 5 cultures contained C. albicans . The assay failed to detect C. glabrata in two of these samples, while three false positive results with C. glabrata , as well as one false positive C. albicans result, were reported.…”