(31 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.
Imipenem/Relebactam has been shown to be active against the Gram-negative aerobic microorganisms listed below according to the FDA label for this antimicrobial agent.
ETEST® IPR can be used to determine the MIC of Imipenem/Relebactam against the following microorganisms:
Active both in vitro and in clinical infections:
- Citrobacter freundii
- Enterobacter cloacae
- Escherichia coli
- Klebsiella aerogenes
- Klebsiella oxytoca
- Klebsiella pneumoniae
- Pseudomonas aeruginosa
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® Imipenem/Relebactam contains a range of imipenem from 0.002 to 32 µg/mL, overlaid with a fixed concentration of 4ug/mL of relebactam.
Here's a breakdown of the acceptance criteria and the study details for the ETEST® Imipenem/Relebactam (IPR) device, based on the provided text:
1. A table of acceptance criteria and the reported device performance
| Performance Metric | Acceptance Criteria (Implicit from Study Design) | Reported Device Performance (ETEST® Imipenem/Relebactam) |
|---|---|---|
| Essential Agreement (EA) | Not explicitly stated, but typically high | Enterobacteriaceae: 95.8% |
| Pseudomonas aeruginosa: 96.0% | ||
| Category Agreement (CA) | Not explicitly stated, but typically high | Enterobacteriaceae: 98.1% |
| Pseudomonas aeruginosa: 96.0% | ||
| Very Major Errors (VME) | Not explicitly stated; typically very low | Enterobacteriaceae: 2.3% (1/44 resistant isolates) |
| Reproducibility | Acceptable results | Acceptable results (reported) |
| Quality Control | Acceptable results | Acceptable results (reported) |
Note: The document refers to "substantially equivalent performance when compared with the CLSI M07-A10 January 2015 broth microdilution reference method, following rules as defined in the FDA Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems; Guidance for Industry and FDA, issued on August 28, 2009 and following specifications as defined in CLSI M100-S28 January 2018." This implies that the acceptance criteria are based on the guidelines and specifications outlined in these documents for establishing substantial equivalence for AST systems. The specific numerical thresholds for EA, CA, and VME set by these guidelines are not explicitly detailed in the provided text but are the underlying acceptance criteria.
2. Sample size used for the test set and the data provenance
- Sample Size for Test Set:
- Enterobacteriaceae:
- Citrobacter freundii: 30 isolates
- Klebsiella aerogenes: 30 isolates
- Enterobacter cloacae: 33 isolates
- Enterobacter cloacae complex: 70 isolates
- Escherichia coli: 165 isolates
- Klebsiella oxytoca: 32 isolates
- Klebsiella pneumoniae: 117 isolates
- Total Enterobacteriaceae: 30 + 30 + 33 + 70 + 165 + 32 + 117 = 477 isolates (Note: one error in the text is 1/44 resistant isolates for VME, but the total number tested for Enterobacteriaceae is 477. It indicates 44 resistant isolates were tested specifically for VME, not for the entire EA/CA.)
- Pseudomonas aeruginosa: The exact number is not explicitly broken down but is part of the overall "Gram negative aerobic bacteria" and the 96.0% EA/CA. The document does not provide a specific number of P. aeruginosa isolates, only the performance result for that category.
- Enterobacteriaceae:
- Data Provenance: "External evaluations were conducted with fresh and stock clinical isolates, as well as a set of challenge strains." This indicates the data is from prospective and retrospective clinical samples that were then tested, likely across multiple sites (implied by "external evaluations"). The country of origin is not specified.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts
The document does not mention the number or qualifications of experts used to establish the ground truth. The ground truth method is the CLSI broth microdilution reference method, which is a standardized laboratory procedure, not typically an expert consensus reading.
4. Adjudication method for the test set
The document does not describe an adjudication method involving experts for the test set. The comparison is made against a standardized laboratory reference method (CLSI broth microdilution).
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 MRMC comparative effectiveness study was done as this device is an in vitro diagnostic (IVD) for antimicrobial susceptibility testing, not an AI-assisted diagnostic for human interpretation. It directly determines MIC values.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done
Yes, this evaluates the standalone performance of the ETEST® system. While a human technician applies the strip and reads the ellipse, the interpretation of the MIC value from the scale is directly determined by the physical outcome (inhibition ellipse) on the strip, comparing it to the CLSI reference method. The "device" in this context refers to the ETEST® strip and its inherent gradient.
7. The type of ground truth used
The ground truth used is the CLSI M07-A10 January 2015 broth microdilution reference method. This is a laboratory reference method that is considered the gold standard for antimicrobial susceptibility testing.
8. The sample size for the training set
The document does not specify a separate "training set" for the ETEST® device. As an IVD, its performance is established against a reference method rather than through a machine learning training paradigm common in AI devices. The "test set" described above is used for performance evaluation, not training.
9. How the ground truth for the training set was established
Not applicable, as no training set (in the machine learning sense) is described. The device's performance is established by direct comparison to the CLSI broth microdilution 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).