(306 days)
VITEK® 2 AST-Gram Negative Ceftazidime is designed for antimicrobial susceptibility testing of Gram negative bacilli and is intended for use with the VITEK® 2 and VITEK® 2 Compact Systems as a laboratory aid in the determination of in vitro susceptibility to antimicrobial agents. VITEK® 2 AST-Gram Negative test. Ceftazidime has been shown to be active against most strains of the microorganisms listed below, according to the FDA label for this antimicrobial.
Active in vitro and in clinical infections:
Citrobacter species Enterobacter species Escherichia coli Klebsiella species Proteus mirabilis Proteus vulgaris Pseudomonas aeruginosa Serratia species
In vitro data are available, but clinical significance is unknown:
Acinetobacter species Citrobacter koseri (formerly Citrobacter diversus) Citrobacter freundii Providencia species (including Providencia rettgeri) Salmonella species Shigella species Yersinia enterocolitica
The VITEK® 2 Gram-Negative Susceptibility Card is intended for use with the VITEK® 2 Systems in clinical laboratories as an in vitro test to determine the susceptibility of clinically significant aerobic Gram-negative bacilli to antimicrobial agents when used as instructed.
The principle of the VITEK® 2 AST cards is based on the microdilution minimum inhibitory concentration (MIC) technique reported by MacLowry and Marsh(1) and Gerlach(0). The VITEK @2 AST card is essentially a miniaturized, abbreviated and automated version of the doubling dilution technique(3).
Each VITEK® 2 AST card contains 64 wells. A control well which only contains microbiological culture media is resident on all cards. The remaining wells contain premeasured portions of a specific antibiotic combined with culture media. The bacterial or yeast isolate to be tested is diluted to a standardized concentration with 0.45 - 0.5% saline before being used to rehydrate the antimicrobial medium within the card. The VITEK® 2 System automatically fills, seals and places the card into the incubator/reader. The VITEK® 2 Compact has a manual filling, sealing and loading operation. The VITEK® 2 Systems monitor the growth of each well in the card over a defined period of time. At the completion of the incubation cycle, a report is generated that contains the MIC value along with the interpretive category result for each antibiotic contained on the card.
VITEK® 2 AST-GN Ceftazidime (≤0.5 - ≥32 ug/mL) has the following concentrations in the card: 1, 2. 4. 8. and 32ug/mL (equivalent standard method concentration by efficacy in ug/mL).
Here's an analysis of the acceptance criteria and study as described in the provided document for the VITEK® 2 AST-Gram Negative Ceftazidime device:
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria for Antimicrobial Susceptibility Test (AST) systems are typically defined in the FDA Class II Special Controls Guidance Document. For this device, the guidance specifies performance metrics for Essential Agreement (EA) and Categorical Agreement (CA), along with limits for Very Major Errors (VME), Major Errors (ME), and Minor Errors (mE).
| Metric | Acceptance Criteria (from FDA Guidance for AST Systems) | Reported Device Performance (VITEK® 2 AST-GN Ceftazidime) |
|---|---|---|
| Overall Essential Agreement (EA) | ≥ 90% | 96.3% (1054/1095) |
| Overall Categorical Agreement (CA) | ≥ 90% | 97.0% (1062/1095) |
| Overall Very Major Errors (VME) | ≤ 1.5% | 3.9% (9/228) * |
| Overall Major Errors (ME) | ≤ 3.0% | 0.7% (6/863) |
| Overall Minor Errors (mE) | ≤ 10.0% | 1.6% (18/1095) |
| Reproducibility | Not explicitly stated in table, presumed to meet standard | 97.04% |
| VME for Enterobacteriaceae | ≤ 1.5% | 0.0% (0/46) |
| ME for Enterobacteriaceae | ≤ 3.0% | 0.5% (3/557) |
| mE for Enterobacteriaceae | ≤ 10.0% | 1.8% (11/605) |
| VME for Pseudomonas aeruginosa | ≤ 1.5% | 5.8% (9/155) *Adjusted to 2.6% (4/155) |
| ME for Pseudomonas aeruginosa | ≤ 3.0% | 1.1% (3/268) |
| VME for Acinetobacter spp. | ≤ 1.5% | 0.0% (0/25) |
| ME for Acinetobacter spp. | ≤ 3.0% | 0.0% (0/33) |
| mE for Acinetobacter spp. | ≤ 10.0% | 10.3% (6/58) |
- Note on VME: The overall VME of 3.9% and 5.8% for Pseudomonas aeruginosa initially exceed the typical ≤1.5% acceptance criterion. However, the document provides an explanation and adjustment for Pseudomonas aeruginosa, stating, "Based on the essential agreement and lack of an intermediate breakpoint for ceftazidime with P. aeruginosa, the adjusted very major error rate for P. aeruginosa is 2.6% (4/155)." It also notes that "Seven of the nine very major errors had MIC values of 8 µg/mL; therefore, alternative testing is required prior to reporting results for P. aeruginosa when the VITEK® 2 MIC value is 8 µg/mL." This suggests a mitigation strategy for these specific results. The overall VME is N/A in the table for specific organisms, making it difficult to fully assess the overall VME without further clarification. The document states "The VITEK® 2 AST-GN Ceftazidime demonstrated acceptable performance".
2. Sample Size Used for the Test Set and Data Provenance
The test set consisted of:
- Total Isolates: 1095 unique organism-drug combinations (based on the overall EA/CA denominators).
- Categories of Isolates: Fresh and stock clinical isolates, as well as a set of challenge strains.
- Data Provenance: The study was an "external evaluation" conducted to compare performance with the CLSI broth microdilution reference method. The document does not explicitly state the country of origin but implies a multi-site clinical evaluation given the "external evaluation" terminology for a device seeking FDA clearance in the US. The study appears to be prospective in nature for collecting new performance data.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
The ground truth was established by the CLSI broth microdilution reference method. This is a laboratory-based, standardized method, not a consensus of human experts in the traditional sense of medical image interpretation. Therefore, the concept of "number of experts" or "qualifications of experts" does not directly apply here as the ground truth is a technical measurement, not an interpretive one.
4. Adjudication Method for the Test Set
Not applicable. The ground truth is a direct technical measurement (CLSI broth microdilution MIC values), not an interpretive assessment requiring adjudication.
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
No, this type of study was not performed. The VITEK® 2 AST-Gram Negative Ceftazidime system is a fully automated antimicrobial susceptibility testing device, directly measuring MIC values and providing interpretive categories (Susceptible, Intermediate, Resistant). It does not involve human "readers" or "AI assistance" in the interpretive process like diagnostic imaging tools would.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done
Yes, this was a standalone performance study. The device, the VITEK® 2 AST-Gram Negative Ceftazidime, functions as an automated system to determine antimicrobial susceptibility. Its performance (MIC readings and categorical interpretations) was evaluated directly against the reference method without human interpretation as part of the operational workflow.
7. The Type of Ground Truth Used
The ground truth used was the CLSI broth microdilution reference method (Clinical and Laboratory Standards Institute). This is a well-established, standardized, and internationally recognized laboratory method for determining the minimum inhibitory concentration of antimicrobial agents.
8. The Sample Size for the Training Set
The document does not explicitly mention a "training set" or its size. Since this is an in vitro diagnostic device with a defined mechanism (microdilution, growth pattern analysis) rather than a machine learning model requiring extensive training data, the concept of a "training set" in the context of AI/ML algorithms may not fully apply. The device's underlying principles are based on established microbiological methods.
9. How the Ground Truth for the Training Set Was Established
Not applicable, as a distinct "training set" with established ground truth for an AI/ML algorithm is not described or likely relevant for this type of automated AST device. The development of such a device relies on established microbiological principles calibrated against reference methods.
§ 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.”