Multicenter Evaluation of the Accelerate PhenoTest BC Kit for Rapid Identification and Phenotypic Antimicrobial Susceptibility Testing Using Morphokinetic Cellular Analysis

Abstract

We describe results from a multicenter study evaluating the Accelerate Pheno system, a first of its kind diagnostic system that rapidly identifies common bloodstream pathogens from positive blood cultures within 90 min and determines bacterial phenotypic antimicrobial susceptibility testing (AST) results within ∼7 h. A combination of fresh clinical and seeded blood cultures were tested, and results from the Accelerate Pheno system were compared to Vitek 2 results for identification (ID) and broth microdilution or disk diffusion for AST. The Accelerate Pheno system accurately identified 14 common bacterial pathogens and two Candida spp. with sensitivities ranging from 94.6 to 100%. Of fresh positive blood cultures, 89% received a monomicrobial call with a positive predictive value of 97.3%. Six common Gram-positive cocci were evaluated for ID. Five were tested against eight antibiotics, two resistance phenotypes (methicillin-resistant Staphylococcus aureus and Staphylococcus spp. [MRSA/MRS]), and inducible clindamycin resistance (MLSb). From the 4,142 AST results, the overall essential agreement (EA) and categorical agreement (CA) were 97.6% and 97.9%, respectively. Overall very major error (VME), major error (ME), and minor error (mE) rates were 1.0%, 0.7%, and 1.3%, respectively. Eight species of Gram-negative rods were evaluated against 15 antibiotics. From the 6,331 AST results, overall EA and CA were 95.4% and 94.3%, respectively. Overall VME, ME, and mE rates were 0.5%, 0.9%, and 4.8%, respectively. The Accelerate Pheno system has the unique ability to identify and provide phenotypic MIC and categorical AST results in a few hours directly from positive blood culture bottles and support accurate antimicrobial adjustment.

Keywords: FISH; MIC; antimicrobial susceptibility testing; bacteremia; blood culture; candidemia; identification; morphokinetic cellular analysis; phenotypic; rapid.

FIG 1

Flowchart of sample disposition after reevaluation of data with the 2017 software update. Footnotes a to g in the flowchart include additional information about the categories. For footnote a, the 560 excluded samples include the following reasons for exclusion: deviation from the protocol (n = 216), experiments halted (n = 26), experiments never run (n = 15), bottle received >8 h after positive result (n = 31), Gram staining shows no organism (n = 24), isolate not received at the reference laboratory (n = 18), isolate received more than 4 days after medium preparation (n = 3), ID reference growth failure (n = 29), nonpure isolate (n = 169), ID reference purity plate failure (n = 6), invalid ID reference result (n = 1), and Accelerate Pheno system run state not “complete” (n = 22). For footnote b with monomicrobic, a single on-panel organism was reported. For footnote c with polymicrobic, this category includes polymicrobial samples where the Accelerate PhenoTest BC kit ID results exactly match the reference results. For footnote d with false-positive, the false-positive category includes monomicrobial or polymicrobial runs containing any false-positive result(s). For footnote e with indeterminate, all indeterminate samples had only indeterminate/negative results. For footnote f with unresolved for fresh samples, of the 48 fresh unresolved false-positive results, 43 showed genus-level agreement, while the remaining five were one S. aureus called CoNS, one S. aureus plus Pantoea species mix called Klebsiella spp., one Pseudomonas putida called Citrobacter spp., one Lactococcus raffinolactis called Streptococcus spp., and one Streptococcus dysgalactiae subsp. equisimilis called E. faecium by the Accelerate Pheno system. For footnote g with unresolved for seeded samples, of the 24 seeded samples containing unresolved false-positive results, 15 showed genus-level agreement, one sample gave two false-positive results, while the remaining nine were one Pantoea sample called Enterobacter spp., one C. koseri sample called Citrobacter spp. plus Proteus spp., two C. koseri samples called Citrobacter spp. plus Klebsiella spp., one C. freundii sample called Citrobacter spp. plus Enterobacter spp., one C. koseri sample called Citrobacter spp. plus E. faecium plus Klebsiella spp., one E. cloacae complex sample called Enterobacter spp. plus P. aeruginosa, one E. faecalis sample called E. faecalis plus E. faecium, and one Streptococcus pyogenes sample called Streptococcus spp. plus E. faecium by the Accelerate Pheno system.