(40 days)
The BD Phoenix™ Automated Microbiology System is intended for the rapid identification and in vitro antimicrobial susceptibility testing of isolates from pure culture of most aerobic and facultative anaerobic gram-negative and gram-positive bacteria of human origin.
The BD Phoenix™ Automated Microbiology System is intended for in vitro quantitative determination of antimicrobial susceptibility by minimal inhibitory concentration (MIC) of most gram-negative aerobic and facultative anaerobic bacteria isolates from pure culture for Enterobacteriaceae and Non-Enterobacteriaceae and most gram-positive bacteria isolates from pure culture belonging to the genera Staphylococcus and Enterococcus.
This premarket notification is for the antimicrobial agent quinupristin/dalfopristin at concentrations of 0.25-4 ug/mL to Gram Positive ID/AST or AST only Phoenix panels. Quinupristin/dalfopristin has been shown to be active in vitro against most strains of microorganisms listed below, as described in the FDA-approved package insert for this antimicrobial agent.
Active In Vitro and in Clinical Infections Against:
Aerobic Gram-positive microorganisms
Enterococcus faecium (vancomycin-resistant and multi-drug resistant strains only) Staphylococcus aureus (methicillin-susceptible strains only)
Active In Vitro Against:
Aerobic Gram-positive microorganisms
Staphylococcus aureus (methicillin-resistant strains) Staphylococcus epidermidis (including methicillin-resistant strains)
Synercid is not active against Enterococcus faecalis. Differentiation of enterococcal species is important to avoid misidentification of Enterococcus faecalis as Enterococcus faecium.
The BD Phoenix Automated Microbiology System (Phoenix System) is an automated system for the rapid identification (ID) and antimicrobial susceptibility testing (AST) of clinically relevant bacterial isolates. The system includes the following components:
- BD Phoenix instrument and software.
- BD Phoenix panels containing biochemicals for organism ID testing and antimicrobial . agents for AST determinations.
- . BD Phoenix ID Broth used for performing ID tests and preparing AST Broth inoculum.
- BD Phoenix AST Broth used for performing AST tests only.
- BD Phoenix AST Indicator solution added to the AST broth to aid in bacterial growth ● determination.
The Phoenix panel is a sealed and self-inoculating molded polystyrene tray with 136 micro-wells containing dried reagents. Organisms for susceptibility testing must be a pure culture and preliminarily identified as a gram-negative or gram-positive isolate. For each isolation equivalent to 0.5 McFarland standard is prepared in Phoenix ID broth.
The Phoenix AST method is a broth based microdilution test. The Phoenix system utilizes a redox indicator for the detection of organism growth in the presence of an antimicrobial agent. Measurements of changes to the indicator as well as bacterial turbidity are used in the determination of bacterial growth. Each AST panel configuration contains several antimicrobial agents with a wide range of two-fold doubling dilution concentrations.
The instrument houses the panels where they are continuously incubated at a nominal temperature of 35°C. The instrument takes readings of the panels every 20 minutes. The readings are interpreted to give an identification of the isolate, minimum inhibitory concentration (MIC) values and category interpretations, S, I, or R (sensitive, intermediate, or resistant).
This document describes the performance of the BD Phoenix™ Automated Microbiology System for Quinupristin/dalfopristin with Gram-positive organisms.
1. Table of Acceptance Criteria and Reported Device Performance:
The acceptance criteria are implicitly defined by the FDA's "Guidance on Review Criteria for Assessment of Antimicrobial Susceptibility Devices," March 8, 2000, which guides the evaluation of Essential Agreement (EA) and Category Agreement (CA). While specific numerical targets for EA and CA are not explicitly stated in the provided text as "acceptance criteria," the study aimed to demonstrate "substantially equivalent performance" to the NCCLS reference method. Typically, FDA guidance for AST devices implies high percentages for both EA and CA to achieve substantial equivalence.
| Performance Metric | Acceptance Criteria (Implicit from FDA Guidance) | Reported Device Performance (Quinupristin/dalfopristin) |
|---|---|---|
| Essential Agreement (EA) | High percentage (e.g., >90% or 95% indicated by "substantially equivalent performance") | 93.8% (n=1456) |
| Category Agreement (CA) | High percentage (e.g., >90% or 95% indicated by "substantially equivalent performance") | 96.8% (n=1456) |
| Intra-site Reproducibility | Greater than 90% | Greater than 90% |
| Inter-site Reproducibility | Greater than 95% | Greater than 95% |
2. Sample Size Used for the Test Set and Data Provenance:
- Test Set Sample Size: 1456 isolates for the combined clinical and challenge set for Essential Agreement (EA) and Category Agreement (CA) calculations.
- Data Provenance: The isolates were sourced from "Clinical, stock and challenge isolates across multiple geographically diverse sites across the United States." This indicates the data is prospective for clinical isolates (compared to a reference method) and potentially retrospective for stock and challenge isolates (with known "expected results"). The country of origin for the clinical data is the United States.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts:
The document does not specify the number or qualifications of experts used to establish the ground truth. The ground truth for clinical isolates was established by the "NCCLS reference broth microdilution method," which is a standardized laboratory procedure, not typically an expert panel. For challenge isolates, the "expected results" were used, implying a pre-defined or confirmed susceptibility profile, though the method of establishment is not detailed.
4. Adjudication Method for the Test Set:
The document does not describe an adjudication method involving multiple readers. The comparison is between the BD Phoenix System's results and the NCCLS reference method or expected results for challenge isolates. It's a direct comparison against a gold standard method rather than an adjudicated consensus among human readers.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done, If So, What Was the Effect Size of How Much Human Readers Improve with AI vs Without AI Assistance:
A Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not performed. This study focuses on the performance of an automated system (BD Phoenix) compared to a reference laboratory method (NCCLS broth microdilution), not on human reader performance with or without AI assistance.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done:
Yes, a standalone study was performed. The BD Phoenix™ Automated Microbiology System is an automated device designed to determine antimicrobial susceptibility without human interpretative intervention in the final result generation beyond initial sample preparation and system loading. The reported performance metrics (EA, CA, reproducibility) are for the algorithm's output directly compared to the NCCLS reference method.
7. The Type of Ground Truth Used:
- For clinical isolates: The ground truth was established by the NCCLS reference broth microdilution method. This is a recognized laboratory gold standard for antimicrobial susceptibility testing.
- For challenge and stock isolates: The ground truth was "expected results," which typically refers to pre-determined or established susceptibility profiles for known strains.
8. The Sample Size for the Training Set:
The document does not specify a sample size for a training set. As this is an automated microbiology system that determines MIC values and categories based on a redox indicator and turbidity changes within a defined panel, it's not a machine learning model in the typical sense that would require a distinct "training set" of images or data for algorithm development. The system's underlying principles are based on established microbiological reactions and spectrophotometric measurements. Any "training" would likely refer to the initial development and calibration of the instrument and its interpretation algorithms, rather than a data-driven machine learning model trained on a specific dataset.
9. How the Ground Truth for the Training Set Was Established:
As no explicit "training set" in the context of a machine learning algorithm is described, the method for establishing its ground truth is also not applicable or detailed in the document. The system's fundamental operational parameters and interpretation algorithms would have been developed and validated against known microbiological reference standards and growth characteristics.
§ 866.1645 Fully automated short-term incubation cycle antimicrobial susceptibility system.
(a)
Identification. A fully automated short-term incubation cycle antimicrobial susceptibility system is a device that incorporates concentrations of antimicrobial agents into a system for the purpose of determining in vitro susceptibility of bacterial pathogens isolated from clinical specimens. Test results obtained from short-term (less than 16 hours) incubation are used to determine the antimicrobial agent of choice to treat bacterial diseases.(b)
Classification. Class II (special controls). The special control for this device is FDA's guidance document entitled “Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems; Guidance for Industry and FDA.”