(66 days)
ETEST® is a manual, quantitative technique for the determination of antimicrobial susceptibility of non-fastidious Gram-negative and Gram-positive aerobic 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. Plazomicin has been shown to be active against most isolates of the bacteria listed below according to the FDA label for this antimicrobial agent.
ETEST® PLZ can be used to determine the MIC of Plazomicin aqainst the following microorganisms:
Active both in vitro and in clinical infections:
- Escherichia coli
- Klebsiella pneumoniae
- Proteus mirabilis
- Enterobacter cloacae
In vitro data are available for the following microorganisms, but clinical significance is unknown:
- Citrobacter freundii
- Citrobacter koseri
- Klebsiella (Enterobacter) aerogenes
- Klebsiella oxytoca
- Morganella morganii
- Proteus vulgaris
- Providencia stuartii
- Serratia marcescens
ETEST® is a thin, inert and non-porous plastic strip carrying the MIC reading scale in µg/mL on one side and a predefined antibiotic gradient on the other side.
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® Plazomicin contains a range of plazomicin from 0.016 to 256 ug/mL.
Here's a summary of the acceptance criteria and study details for the ETEST® Plazomicin (PLZ) device, based on the provided text:
1. Table of Acceptance Criteria and Reported Device Performance
The device performance is compared to the CLSI M07-A11 broth microdilution reference method. The acceptance criteria are implicitly derived from the CLSI guidance documents and FDA's Class II Special Controls Guidance Document for Antimicrobial Susceptibility Test (AST) Systems.
| Performance Metric | Acceptance Criteria (Implicit from Guidance) | Reported Device Performance (ETEST® Plazomicin) |
|---|---|---|
| Essential Agreement (EA)a | > 90% | 99.0% |
| Category Agreement (CA) | > 90% (with some exceptions noted for specific organisms where EA is high and errors are minor) | 92.8% |
| Reproducibility | Results within expected range > 95% of the time | Best-case: 100%, Worst-case: 100% |
| Quality Control | Results within expected range > 95% of the time | Results within expected range > 95% of the time |
a) EA = % of MIC values within ± 1 dilution of the reference method.
2. Sample Size Used for the Test Set and Data Provenance
- Test Set Sample Size: The performance data for Enterobacteriaceae included a total of 605 strains.
- Breakdown by organism: Escherichia coli (78), Klebsiella pneumoniae (89), Proteus mirabilis (63), Enterobacter cloacae (60), Citrobacter freundii (59), Citrobacter koseri (34), Klebsiella (Enterobacter) aerogenes (38), Klebsiella oxytoca (39), Morganella morganii (31), Proteus vulgaris (34), Providencia stuartii (35), and Serratia marcescens (38).
- Data Provenance: "External evaluations were conducted with fresh and stock clinical isolates, as well as a set of challenge strains." This indicates a mix of retrospective (stock clinical isolates) and prospective (fresh clinical isolates) data, along with curated challenge strains. The country of origin is not specified but implicitly involves clinical settings relevant to the device's intended use.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
Not explicitly stated. The ground truth was established by comparing the ETEST® Plazomicin results with the CLSI broth microdilution reference method. This method itself is the gold standard, and its execution and interpretation typically rely on trained laboratory personnel rather than "experts" in the sense of physicians or radiologists adjudicating images.
4. Adjudication Method for the Test Set
Not applicable in the traditional sense for this type of device. The study design involves direct comparison to a reference method (CLSI broth microdilution) rather than expert adjudication of results. Discrepancies (e.g., categorical errors) are noted and explained.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done
No, an MRMC comparative effectiveness study was not done. This device is an antimicrobial susceptibility test system, not an imaging device requiring human reader interpretation in the same way. The evaluation focuses on the agreement between the test strip and a reference laboratory method.
6. If a Standalone (i.e. algorithm only without human-in-the loop performance) Was Done
This is a standalone device performance study. The ETEST® strip visually provides the Minimum Inhibitory Concentration (MIC) value, which is then interpreted. While a human reads the result from the strip, the performance study itself assesses the accuracy of the strip's ability to generate that MIC in comparison to a reference method. It's not an "algorithm" in the typical software sense, but the device's inherent functional performance is evaluated independently.
7. The Type of Ground Truth Used
The ground truth used was the CLSI M07-A11 broth microdilution reference method. This is considered the gold standard for determining antimicrobial susceptibility.
8. The Sample Size for the Training Set
The document does not explicitly mention a separate "training set" in the context of device development or algorithm training. The performance study focuses on the evaluation of the finished product using clinical and challenge isolates against a reference method.
9. How the Ground Truth for the Training Set Was Established
As no training set is explicitly described for algorithm development, this point is not applicable. The device's underlying mechanism is a physical chemical gradient, not a machine learning algorithm that requires a separate training set. The "development" or "calibration" of the ETEST® strips would involve internal studies to ensure the accuracy of the gradient, likely using similar reference methods.
§ 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).