(60 days)
Etest® is a quantitative technique for determination of antimicrobial susceptibility of both non-fastive and Gram-positive aerobic bacteria such as Enterobacteriaceae, Pseudomonas, Staphylococcus, and Enterococcus species and fastidious bacteria, such as anaerobes, N. gonorhoeae, S. pneumoniae, Streptococcus and Haemophilus species. 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 as tested on agar media using overnight incubation.
Ceftazidime/Avibactam has been shown to be active against the Gram negative aerobic microorganisms listed below. according to the FDA label for this antimicrobial agent.
Etest® CZA can be used to determine the MIC of Ceftazidime/Avibactam against the microorganisms listed below:
Active both in vitro and in clinical infections: Citrobacter freundii Enterobacter cloacae
Escherichia coli Klebsibacter oxytoca Klebsiella pneumoniae Proteus mirabilis Pseudomonas aeruginosa
The following in vitro data are available, but clinical significance is unknown: Citrobacter koseri Enterobacter aerogenes Morganella morganii Providencia rettgeri Providencia stuartii Serratia marcescens
Etest® is a thin, inert and non-porous plastic strip carrying on one side (A) the MIC reading scale in ug/mL, and on the other side (B) 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.
The acceptance criteria and study proving the device meets the acceptance criteria are detailed below based on the provided document.
1. Acceptance Criteria and Reported Device Performance
The device performance is assessed by comparing its Minimum Inhibitory Concentration (MIC) determination against a reference method. The key metrics are Essential Agreement (EA) and Category Agreement (CA).
| Performance Metric | Acceptance Criteria (Implied) | Reported Device Performance |
|---|---|---|
| Enterobacteriaceae: | ||
| % Essential Agreement (EA) | High agreement expected | 99.1% |
| % Category Agreement (CA) | High agreement expected | 99.6% |
| Pseudomonas aeruginosa: | ||
| % Essential Agreement (EA) | High agreement expected | 99.3% |
| % Category Agreement (CA) | High agreement expected | 99.3% |
Note: The document states "acceptable performance" for the reported values, implying that these percentages met the pre-defined (but not explicitly stated in this excerpt) acceptance thresholds set by the FDA Class II Special Controls Guidance Document and CLSI standards. The document also notes that the overall very major error rate for Enterobacteriaceae was 4.4% but was adjusted to 0.0% because “the two very major errors were one dilution apart from the reference method and as such fall within essential agreement.”
2. Sample Size and Data Provenance
The document does not explicitly state the exact sample size for the test set. However, it indicates that the external evaluations were conducted with:
- "fresh and stock clinical isolates"
- "a set of challenge strains"
The data provenance is not explicitly stated in terms of country of origin. The study was retrospective/prospective in nature as it involved collecting existing (stock) and newly acquired (fresh clinical) isolates.
3. Number of Experts and Qualifications
The document does not provide information on the number of experts used or their qualifications for establishing the ground truth.
4. Adjudication Method for the Test Set
The document does not specify any adjudication method used for the test set. The comparison was made against the "CLSI M07-A10 January 2015 broth microdilution reference method."
5. Multi Reader Multi Case (MRMC) Comparative Effectiveness Study
A Multi-Reader, Multi-Case (MRMC) comparative effectiveness study was not applicable in this context. This device (Etest Ceftazidime/Avibactam) is an in vitro diagnostic (IVD) antimicrobial susceptibility test system, not an AI-assisted diagnostic imaging or similar system where human reader improvement with AI assistance would be measured. The study described focuses on the device's accuracy in determining MIC values compared to a reference method, not on human interpretation.
6. Standalone Performance
Yes, a standalone performance study was done. The performance results (Essential Agreement and Category Agreement) presented in Table 1 reflect the performance of the Etest device itself, without human interpretation variability being a primary focus beyond the reading of the MIC value from the strip. The device directly determines the MIC.
7. Type of Ground Truth Used
The ground truth used was the CLSI (Clinical and Laboratory Standards Institute) M07-A10 January 2015 broth microdilution reference method. This is a recognized phenotypic method for determining antimicrobial susceptibility, considered the gold standard for MIC determination.
8. Sample Size for the Training Set
The document does not provide information about a separate "training set" or its sample size. For an IVD like an AST system, the "training" typically refers to the development and optimization of the physical strip's design and gradient, rather than an AI/machine learning training set. The performance data presented are from validation studies.
9. How the Ground Truth for the Training Set Was Established
Given that this is an in vitro diagnostic device and not an AI/ML algorithm that undergoes explicit "training" on a dataset, the concept of establishing ground truth for a training set does not directly apply here in the same way it would for AI in medical imaging. The development of Etest relies on established microbiological principles and validated manufacturing processes to create the predefined antibiotic gradient. The performance is then validated against a recognized reference method.
§ 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).