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The eQUANT System is an automated inoculum preparation system that uses potentiometric sensing of oxidation-reduction potential changes due to pathogen metabolism to generate a 0.5 McFarland-equivalent suspension (the eMcFarland or eMcF) from positive blood culture samples that can be used for direct, qualitative in vitro susceptibility testing by the agar disk diffusion test method (Kirby-Bauer). Samples are processed directly from blood culture samples identified as positive by a continuous monitoring blood culture system and confirmed as Gram-negative rods by Gram stain. Organism identification must be confirmed by an FDA cleared device for direct testing from positive blood culture before processing samples on the eQUANT System.

Evaluation of the eQUANT System's inoculum preparation was conducted for use with agar disk diffusion susceptibility testing and performance was demonstrated for the following antimicrobial agents with Enterobacterales species, Acinetobacter species and Pseudomonas aeruginosa as identified below:

Amoxicillin/clavulanate- Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis

Ampicillin- Escherichia coli

Aztreonam- Citrobacter freundii, Enterobacter cloacae, Escherichia aerogenes, Klebsiella oxytoca, Klebsiella pneumoniae, Proteus mirabilis, Proteus vulgaris, Serratia marcescens, and Pseudomonas aeruginosa

Cefazolin- Klebsiella pneumoniae

Cefepime- Enterobacter cloacae, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Proteus vulgaris, Serratia marcescens, and Pseudomonas aeruginosa

Ceftriaxone- Citrobacter freundii, Enterobacter cloacae, Escherichia aerogenes, Klebsiella oxytoca, Klebsiella pneumoniae, Proteus mirabilis, Proteus vulgaris, Serratia marcescens

Ertapenem- Citrobacter freundii, Enterobacter cloacae, Escherichia coli, Klebsiella axytoca, Klebsiella pneumoniae, Proteus mirabilis, Proteus vulgaris, Serratia marcescens

Gentamicin- Citrobacter freundii, Enterobacter cloacae, Escherichia coli, Klebsiella axytoca, Klebsiella pneumoniae, Proteus mirabilis, Proteus vulgaris, Serratia marcescens, and Pseudomonas aeruginosa

Levofloxacin- Citrobacter freundii, Enterobacter cloacae, Escherichia coli, Klebsiella oxytoca, Klebsiella pneumoniae, Proteus mirabilis, Proteus vulgaris, Serratia marcescens, and Pseudomonas aeruginosa

Meropenem- Acinetobacter spp., Citrobacter freundii, Enterobacter cloacae, Escherichia coli, Klebsiella oxytoca, Klebsiella pneumoniae, Proteus mirabilis, Proteus vulgaris, Serratia marcescens, and Pseudomonas aeruginosa

Piperacillin/tazobactam- Acinetobacter spp., Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Proteus vulgaris, Serratia marcescens, and Pseudomonas aeruginosa

Tobramycin- Citrobacter freundii, Enterobacter cloacae, Escherichia aerogenes, Klebsiella oxytoca, Klebsiella pneumoniae, Proteus vulgaris, Serratia marcescens, and Pseudomonas aeruginosa

Susceptibility test results are intended to be used in conjunction with other clinical and laboratory findings. Standard laboratory protocols for processing positive blood cultures should be followed to ensure availability of isolates for supplemental testing as needed. Additionally, subculture of positive blood culture is necessary for the susceptibility testing of organisms present in polymicrobial samples, for testing antimicrobial agents and species not indicated for testing with the device, for epidemiologic testing, and for recovery of organisms present in microbial samples.

Device Description

The eQUANT™ System is an automated system that uses potentiometric sensing of changes in oxidationreduction potential (ORP) during pathogen metabolism to prepare an organism concentration equivalent to a 0.5 McFarland (1-2e8 CFU/ml ± 0.6 log) directly from a positive blood culture. The eQUANT™ System consists of four components: the eQUANT™ Instrument, a single use eTube™ Disposable, a single use eQUANT™ Reagent tube (CAMHB with antifoam), and a workflow tray.

The eQUANT™ System processes a single positive blood culture sample at a time. Before processing on the eQUANT™ System, the positive blood culture is confirmed as Gram-negative rods by Gram stain, and a rapid FDA-cleared identification (ID) method for testing from positive blood culture is performed to confirm organism ID. Mixed cultures or organisms identified that are not included in the eQUANT™ System indications for use should not be processed on the eQUANT™ System. Positive blood cultures must be processed immediately on the eQUANT™ System or within 12 hours of blood culture bottle positivity should delays be unavoidable. Once the organism ID is confirmed, 1 mL of eQUANT™ Reagent (cation-adjusted Mueller Hinton broth (CAMHB) supplemented with antifoam (0.0015%) to reduce air bubble formation) is added to the eTube™ Disposable, followed by the addition of 34 µL of the positive blood culture. The eTube™ Disposable with diluted sample is vortexed and then placed in the eQUANT™ System for incubation.

Once inserted, the eTube™ Disposable sits in a thermal module which is heated to 37°C ± 2°C to grow the bacteria to a concentration equivalent to a 0.5 McFarland, or eMcF). The eQUANT™ Sensor located in the eTube™ Disposable is an ORP sensor consisting of two electrode components, which both come into direct contact with the diluted positive blood culture sample. The eQUANT™ ORP sensor responds to changes in the ORP during pathogen growth/metabolism. As the concentration of microorganisms in the sample increases, the growth media becomes reduced, and the voltage measured by the ORP sensor becomes more negative. With the organism ID of the tested sample and the blood culture bottle type as inputs to the system, the algorithm is applied to the real-time voltage measurements to determine the point in time at which the organism concentration reaches a level equivalent to a standard 0.5 McFarland. At the endpoint, the sample immediately starts to cool down to 15°C ± 2°C to inhibit further growth. The sample can be held for up to one (1) hour on the instrument, before being used for downstream Disk Diffusion AST testing.

AI/ML Overview

Here's a breakdown of the acceptance criteria and study information for the eQUANT System, based on the provided document:

Acceptance Criteria and Device Performance

Acceptance Criteria (eQUANT System)	Reported Device Performance
Reproducibility of eMcFarland Concentration: ≥95% agreement that the eMcFarland concentration falls within 2.51e7 – 7.96e8 CFU/mL.	98.9% overall agreement based on eMcFarland concentration across sites, operators, runs, instruments, and lots. (Table 1)
Sample Stability (Positive Blood Culture): eMcFarland concentration meets 2.51e7 – 7.96e8 CFU/mL after specified holding times.	All eMcFarland colony counts met defined acceptance criteria. Positive blood culture bottles are stable for use on the eQUANT System for up to 12 hours when held on the blood culture instrument (35°C) or benchtop (room temperature). (Table 2)
eMcFarland Stability: eMcFarland concentration meets 2.51e7 – 7.96e8 CFU/mL after specified holding times post-processing.	eQUANT System generated eMcFarlands are stable for up to one (1) hour on the eQUANT Instrument, held at 15°C, and for up to 10 minutes after removal, held at room temperature. (Table 3)
Blood Culture Bottle Equivalency (eMcFarland Concentration): All eMcFarland concentrations meet 2.51e7 – 7.96e8 CFU/mL from various blood culture bottle media types.	All eMcFarland colony counts for all organisms and bottle types evaluated met defined acceptance criteria (2.51e7 – 7.96e8 CFU/mL). (Table 4)
Blood Culture Bottle Equivalency (Disk Diffusion AST): >95% CA when compared to standard 0.5 McFarland inoculum AST for A. baumannii and P. aeruginosa. >95% CA for Enterobacterales (exceptions noted).	Performed as follows: - A. baumannii: >95% CA for all bottle types assessed (100% CA).- P. aeruginosa: >95% CA for all bottle types except BD BACTEC Aero Plus (90.5% CA, with two minor errors). The two minor error eQUANT™ zone diameters were less than 3 mm difference compared to the standard method, considered acceptable.- Enterobacterales: >95% CA only obtained for BACT/ALERT SN (96.9% CA). Other bottle types showed 90-93% CA due to minor errors. The majority (93.8%) of error results had zone diameters ≤3 mm difference compared to the standard method, considered acceptable. 63/64 minor errors were due to a single K. pneumoniae isolate. (Table 4)
Interfering Substances (eMcFarland Concentration): All eMcFarland concentrations meet 2.51e7 – 7.96e8 CFU/mL in the presence of interferents.	All resulting eMcFarland concentrations met defined acceptance criteria (2.51e7 – 7.96e8 CFU/mL). (Tables 5-6)
Interfering Substances (Downstream AST): No reproducible interference observed in downstream AST testing.	No reproducible interference was observed. (Tables 5-6). High concentrations of hemoglobin (A. baumannii, P. aeruginosa) and platelets (P. aeruginosa) initially caused aborted runs. At decreased interferent concentrations, valid eMcFarlands were generated, and AST results were as expected. Minor errors in Ampicillin and Chloramphenicol were deemed acceptable due to zone diameter differences ≤ 3 mm.
Carryover: No bacterial carryover between runs.	No carryover was observed, as evidenced by monomicrobial cultures and the expected organism morphology during alternating runs of E. coli and P. aeruginosa.
Method Comparison (eMcFarland Concentration): ≥95% of eMcFarland colony counts fall within 2.51e7 – 7.96e8 CFU/mL.	99.1% of PBC samples were within the expected colony count range (219/221 samples). Two samples (one A. spp., one P. aeruginosa) were outside the range, but showed no errors in Disk Diffusion results. (Table 8)
Method Comparison (Disk Diffusion AST): - Overall CA: ≥95%- VME: ≤1%- ME: ≤1.5%(for each antimicrobial agent/organism group combination)	Most antibiotic/group combinations met overall acceptance criteria. - Exceptions to ≥95% CA: Amoxicillin/Clavulanate/Enterobacterales (94%), Cefazolin/Enterobacterales (85% - removed from Indications for Use for E. coli and P. mirabilis due to <90% CA), Cefepime/Enterobacterales (92% - removed from Indications for Use for C. freundii and K. aerogenes due to <90% CA), Piperacillin/Tazobactam/Enterobacterales (94%). These were considered acceptable if zone diameter differences were ≤3mm. - Exceptions to ≤1% VME: Gentamicin/Enterobacterales (3.85% - considered acceptable as zone diameters for major errors were ≤3 mm difference compared to standard). - Exceptions to ≤1.5% ME: Cefepime/Pseudomonas aeruginosa (9.52%). (Table 9) Other specific instances of minor/major errors were deemed acceptable based on zone diameter differences (≤3mm) or being single occurrences.

Study Details

The document describes five main studies to prove the device meets acceptance criteria: Reproducibility, Sample Stability, Blood Culture Bottle Equivalency, Interfering Substances, and Method Comparison.

2. Sample Size Used for the Test Set and Data Provenance

Reproducibility Study:
- Sample Size: 462 eMcFarlands (72 replicates per organism for 5 organisms, and 102 replicates for Acinetobacter baumannii due to repeat testing). A panel of six organisms was used.
- Data Provenance: Contrived positive blood culture samples (contrived in blood culture bottles with human blood added).
Sample Stability Study:
- Sample Size: A panel of five organisms. The number of samples for each condition (organism, storage condition, time point) was tested in triplicate. Total samples not explicitly stated but implied to be 5 organisms x 2 storage conditions x 3 time points per condition x 3 replicates = 90 PBC stability tests. eMcFarland stability was also tested for these 5 organisms at various post-removal time points.
- Data Provenance: Contrived positive blood culture samples (contrived in blood culture bottles with human blood added).
Blood Culture Bottle Equivalency Study:
- Sample Size: A panel of eight organisms was contrived into various blood culture bottle types. Each organism/bottle type was tested in triplicate. (e.g., Enterobacterales: 9 bottle types * 96 total results = 864 results; P. aeruginosa: 4 bottle types * 21 total results = 84 results; A. baumannii: 4 bottle types * 24 total results= 96 results).
- Data Provenance: Contrived positive blood culture samples (contrived in blood culture bottles with human blood added).
Interfering Substances Study:
- Sample Size: A panel of nine organisms. Tests were conducted with and without potential interferents. Interferents include 10 endogenous substances and 10 antibiotics. When acceptance criteria were not met, repeat testing was performed in triplicate. (e.g., Table 5 shows overall CA results for endogenous substances ranging from 172-191 total tests, and Table 6 for antibiotics ranging from 6-66 tests.)
- Data Provenance: Contrived positive blood culture samples (contrived in blood culture bottles with human blood added).
Method Comparison Study:
- Sample Size: 567 positive blood culture samples included in performance analysis (out of 578 enrolled). Colony counts were performed on 221 samples of these.
- Data Provenance:
  - 42 (7.4%) prospective clinical samples: Leftover, de-identified. Confirmed by Gram stain (Gram-negative rods) and an FDA-cleared ID method.
  - 515 (90.8%) contrived with stock isolates.
  - 10 (1.8%) contrived with challenge isolates (with known antimicrobial resistance, provided by Avails Medical).

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications

The document does not explicitly state the number of experts used or their specific qualifications for establishing ground truth, especially for the method comparison study. However, the ground truth for AST performance (method comparison) was established by comparing eQUANT System results to results generated from a traditional 0.5 McFarland standard prepared from isolated colonies according to CLSI guidelines (CLSI M02-A12). This implies standard laboratory practices using trained personnel, but not necessarily "experts" in the sense of external adjudicators.

4. Adjudication Method for the Test Set

The document does not mention an explicit adjudication method like 2+1 or 3+1. The ground truth for AST results in the method comparison study was based on comparison to a "standard (std) inoculum" prepared according to CLSI guidelines. Any discrepancies would likely have been analyzed by the study team, but an formal adjudication process involving multiple external experts is not described.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done

No, an MRMC comparative effectiveness study was not done. The studies focused on the performance of the device's inoculum preparation and its impact on subsequent in vitro AST results, not on how human readers' diagnostic accuracy improves with or without AI assistance. The eQUANT System is a tool for preparing inoculum for AST, not an AI-assisted diagnostic tool interpreted by human readers.

6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done

Yes, the primary performance evaluation of the eQUANT System is a standalone (algorithm only) assessment of its ability to produce a 0.5 McFarland equivalent inoculum. The system automatically processes the blood culture sample and its algorithm determines when the target concentration is reached. The downstream Disk Diffusion AST is then performed by laboratory personnel using the eMcFarland generated by the system. The performance metrics (eMcFarland concentration, CA, VME, ME rates) directly reflect the device's accuracy in generating an appropriate inoculum that yields reliable AST results.

7. The Type of Ground Truth Used

For eMcFarland Concentration: The ground truth was colony counts (CFU/mL) obtained by plating the prepared eMcFarlands and enumerating colonies. The target range was 2.51e7 – 7.96e8 CFU/mL, which corresponds to the 0.5 McFarland standard.
For Disk Diffusion AST: The ground truth was the AST results generated from a traditional 0.5 McFarland standard prepared from isolated colonies according to CLSI guidelines (CLSI M02-A12). This serves as the reference standard for categorical interpretations (Susceptible/Intermediate/Resistant - S/I/R) using FDA-recognized breakpoints (Antimicrobial Susceptibility Test Interpretive Criteria/STIC) and CLSI M100.

8. The Sample Size for the Training Set

The document does not explicitly describe a "training set" in the context of machine learning model training. The eQUANT System uses an algorithm based on potentiometric sensing of oxidation-reduction potential changes. While this algorithm would have been developed and optimized, the document focuses on validation studies rather than the specifics of algorithm development data. There's no specific mention of a separate, distinct "training set" for an AI aspect used by the device that would be typically reported alongside a test set. The algorithm uses "species-specific and blood culture bottle-specific algorithms" as inputs to determine the endpoint.

9. How the Ground Truth for the Training Set Was Established

As noted above, a distinct "training set" with established ground truth, as defined in a typical AI/ML context, is not explicitly detailed. The fundamental principle of the eQUANT system is to match a 0.5 McFarland equivalent concentration. Therefore, any "training" or development of its algorithms would have involved generating inoculum suspensions and verifying their concentration through methods like direct colony counts (CFU/mL) to ensure the algorithm correlates ORP changes to the desired bacterial density.

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