(91 days)
ETEST® is a manual, quantitative technique for determination of antimicrobial susceptibility of non-fastidious Gram-negative and Gram-positive aerobic bacteria and fastidious bacteria. The system comprises a predefined antibiotic gradient which is used to determine the Minimum Inhibitory Concentration (MIC, in ug/mL) of different antimicrobial agents against microorganisms tested on agar media after overnight incubation.
Piperacillin/Tazobactam has been shown to be active against the Gram-negative aerobic microorganisms listed below according to the FDA label for this antimicrobial agent.
ETEST® P/T can be used to determine the MIC of Piperacillin/Tazobactam against the following microorganisms:
Active both in vitro and in clinical infections: Acinetobacter baumannii Escherichia coli Klebsiella pneumoniae Pseudomonas aeruginosa
In vitro data are available for the following microorganisms, but clinical significance is unknown:
Citrobacter koseri Morganella morganii Proteus mirabilis Proteus vulgaris Serratia marcescens Providencia stuartii Providencia rettgeri Salmonella enterica
ETEST® is a thin, inert and non-porous plastic strip carrying on one side the MIC reading scale in ug/mL, and on the other side a predefined antibiotic gradient.
When the strip is applied to an inoculated agar surface, the preformed antibiotic gradient immediately transfers into the agar matrix, then forming a stable, continuous and exponential gradient of antibiotic concentrations directly underneath the strip. Bacterial growth becomes visible during incubation, and a symmetrical inhibition ellipse centered along the strip appears. The MIC value is read from the scale in terms of ug/mL at complete inhibition of bacterial growth, where the pointed end of the ellipse intersects the strip.
ETEST® Piperacillin/Tazobactam contains a range of piperacillin from 0.016 to 256 ug/mL, overlaid with a fixed concentration of 4 ug/mL of tazobactam.
This document describes the performance of the ETEST® Piperacillin/Tazobactam (P/T) device in determining antimicrobial susceptibility.
1. Table of acceptance criteria and the reported device performance:
| Performance Metric | Acceptance Criteria (Implicit from Guidance) | Reported Device Performance |
|---|---|---|
| Essential Agreement (EA) | Generally, >90% (based on FDA guidance for AST systems) | Enterobacteriaceae: 95.8% |
| Pseudomonas aeruginosa: 98.3% | ||
| Acinetobacter spp.: 91.6% | ||
| Category Agreement (CA) | Generally, >90% (based on FDA guidance for AST systems) | Enterobacteriaceae: 93.3% |
| Pseudomonas aeruginosa: 93.3% | ||
| Acinetobacter spp.: 89.2% |
Note: The document references the "FDA Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems; Guidance for Industry and FDA, issued on August 28, 2009" and "CLSI M100-S28 January 2018," which would contain the specific acceptance criteria for Essential Agreement and Category Agreement. The reported performance is directly quoted from Table 1.
2. Sample size used for the test set and the data provenance:
- Sample Size (Test Set):
- Enterobacteriaceae: The performance data for Enterobacteriaceae includes: E. coli (168), K. pneumoniae (190), C. koseri (46), M. morganii (41), P. mirabilis (41), P. vulgaris (31), S. marcescens (47), P. stuartii (36), P. rettgeri (28), and S. enterica (31). The total number of unique isolates for Enterobacteriaceae is the sum of these values: 168 + 190 + 46 + 41 + 41 + 31 + 47 + 36 + 28 + 31 = 659 isolates.
- P. aeruginosa and Acinetobacter spp.: Specific numbers for these categories are not provided beyond the overall performance percentages.
- The study utilized "fresh and stock clinical isolates, as well as a set of challenge strains." This implies a diverse collection of organisms.
- Data Provenance: The document does not explicitly state the country of origin. It indicates "External evaluations were conducted with fresh and stock clinical isolates, as well as a set of challenge strains." This suggests a retrospective and potentially prospective collection of real-world clinical isolates for the test set.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
This information is not provided in the document. The ground truth method (CLSI broth microdilution) is a standardized laboratory procedure, not typically relying on expert interpretation in the same way an imaging study would.
4. Adjudication method (e.g., 2+1, 3+1, none) for the test set:
This information is not applicable for this type of device and study. The ground truth (broth microdilution) is a quantitative laboratory measurement, not subject to subjective expert interpretation 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:
A multi-reader multi-case (MRMC) comparative effectiveness study was not done. This device is an Antimicrobial Susceptibility Test (AST) system, which provides quantitative MIC values and categorical interpretations (Susceptible, Intermediate, Resistant). It is not an AI-assisted diagnostic imaging or interpretation tool for human readers.
6. If a standalone (i.e., algorithm only without human-in-the-loop performance) was done:
The study assessed the standalone performance of the ETEST® Piperacillin/Tazobactam device. The device itself (the strip and its resulting inhibition ellipse) generates the result, which is then read by a trained user to determine the MIC. While a human reads the strip, the performance metrics (Essential Agreement, Category Agreement) refer to the accuracy of the device's output compared to the reference method, essentially evaluating the "algorithm only" in generating the gradient and inhibition pattern. The document mentions optional inoculator and ETEST® strip applicator, but clarifies that "swabs were used for plate inoculation/streaking and forceps were used for ETEST® strip application" in the clinical studies, indicating manual procedures for the setup, but the core measurement is from the device.
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.):
The ground truth used was the CLSI M07-A11 January 2018 broth microdilution reference method. This is a recognized standard laboratory method for determining antimicrobial susceptibility.
8. The sample size for the training set:
The document does not explicitly mention a training set sample size. For AST devices, performance studies typically focus on an independent test set compared to a reference method. While there's a development process for the ETEST® strip formulation, the submitted data pertains to its validation against established standards, not a machine learning model's training.
9. How the ground truth for the training set was established:
As no explicit training set is mentioned in the context of machine learning, the question of how its ground truth was established is not applicable here. The "development" of the ETEST® device would have involved ensuring the stability and accuracy of the antibiotic gradient, but this is a manufacturing/chemistry process, not a data-driven model training process with ground truth labels.
§ 866.1640 Antimicrobial susceptibility test powder.
(a)
Identification. An antimicrobial susceptibility test powder is a device that consists of an antimicrobial drug powder packaged in vials in specified amounts and intended for use in clinical laboratories for determining in vitro susceptibility of bacterial pathogens to these therapeutic agents. Test results are used to determine the antimicrobial agent of choice in the treatment of bacterial diseases.(b)
Classification. Class II (performance standards).