(223 days)
Remel Spectra™ ESBL is a selective and differential growth medium for use in primary isolation and presumptive identification of Extended Spectrum β Lactamase (ESBL)-producing Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca and Proteus mirabilis to aid in prevention and control of these bacteria in a healthcare setting. Testing may be performed from either perirectal swabs or fresh stool specimens. Remel Spectra™ ESBL is not intended to diagnose ESBL infection, or to guide or monitor treatment.
Do not report Spectra™ ESBL positive screening results. Subculture of presumptive positive colonies to non-selective medium (e.g. Tryptic Soy Agar with 5% sheep blood) is required for organism identification, confirmatory testing for ESBL, susceptibility testing and epidemiological typing.
A lack of growth or the absence of pink, blue-turquoise-green or tan colonies on Spectra™ ESBL does not preclude the presence of ESBL producing organisms.
Spectra™ ESBL contains a combination of antibacterial agents which aid in inhibiting non-ESBL Enterobacteriaceae and suppress the growth of some AmpC organisms and other non-ESBL flora. Peptones supply amino acids and essential nutrients which promote the growth of enteric gram-negative bacilli. Sodium chloride is a source of essential electrolytes and maintains osmotic equilibrium. Phosphate buffers are added to maintain the pH.
A mixture of chromogens forms a substrate for two enzymes: βgalactosidase and glucuronidase that are differentially expressed in different species of bacteria resulting in blue/turquoise-green or pink colonies. Other ESBL-producing organisms that do not utilize the chromogenic substrates may produce tan colonies through deamination of tryptophan. Non-target organisms generally appear cream colored or are naturally pigmented green or brown.
The provided text describes the performance evaluation of the Remel Spectra™ ESBL device. The following information details the acceptance criteria and study findings:
1. Table of Acceptance Criteria and Reported Device Performance:
| Performance Metric | Acceptance Criteria (Implicit) | Reported Device Performance (18 hours) | Reported Device Performance (24 hours) |
|---|---|---|---|
| Sensitivity | High agreement with reference method for ESBL-producing organisms | 98.5% (95.8-99.5% CI) | 99.0% (96.5-99.7% CI) |
| Specificity | High agreement with reference method for non-ESBL-producing organisms | 89.6% (87.6-91.3% CI) | 88.7% (86.6-90.4% CI) |
| Positive Percent Agreement (PPA) | High agreement of Spectra Colony ID and ESBL Phenotype with reference method | 99.0% (96.5-99.7% CI) | 100.0% (98.2-100% CI) |
| Negative Percent Agreement (NPA) | High agreement of Spectra Colony ID and ESBL Phenotype with reference method | 89.8% (87.8-91.5% CI) | 88.9% (86.9-90.7% CI) |
| Reproducibility (Positive Agreement) | 100% agreement with expected colony color for ESBL-producing organisms | 100% (210/210) | N/A (Reproducibility done for overall ESBL detection) |
| Reproducibility (Negative Agreement) | No false positive results with non-ESBL-producing strains | 100% (60/60) | N/A (Reproducibility done for overall ESBL detection) |
| Reactivity | Expected growth and colony color for confirmed ESBL-producing strains | 100% (all 48 tested strains grew with expected colony color) | N/A |
| Cross-reactivity | Most non-target organisms (common fecal flora) should not grow; those that do should be differentiable or have high cephalosporin MICs | 19 non-ESBL Enterobacteriaceae and 3 non-Enterobacteriaceae grew. All but 3 of these had high cephalosporin MICs. | N/A |
Note: The document implicitly defines "high agreement" as the acceptance criterion for sensitivity, specificity, PPA, and NPA, demonstrated by the reported percentages and confidence intervals. Reproducibility, reactivity, and cross-reactivity have explicit criteria.
2. Sample Size Used for the Test Set and Data Provenance:
- Sample Size: A total of 1176 prospective rectal swab (439) and fecal (737) surveillance specimens.
- Data Provenance: Clinical data collected prospectively from three different clinical hospitals in the United States.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications:
The document does not explicitly state the number of experts or their qualifications for establishing the ground truth. It mentions that the ground truth was "obtained from growth on MacConkey agar with a 10μg cefpodoxime disk […], followed by biochemical identification and disk diffusion phenotypic confirmatory antimicrobial susceptibility testing for ESBLs as outlined in the Clinical and Laboratory Standards Institute document M100-S23." This implies adherence to a standardized protocol rather than individual expert consensus for each case.
4. Adjudication Method for the Test Set:
The document does not describe an adjudication method involving multiple human readers for the test set. The reference method (ground truth) appears to be based on a standardized laboratory protocol.
5. If a Multi Reader Multi Case (MRMC) Comparative Effectiveness Study Was Done:
No, a multi-reader multi-case (MRMC) comparative effectiveness study was not explicitly mentioned or performed. The study evaluates the performance of the Remel Spectra™ ESBL device against a laboratory-based reference method, not against human readers with or without AI assistance.
6. If a Standalone (Algorithm Only Without Human-in-the-Loop Performance) Was Done:
This study directly assesses the standalone performance of the Remel Spectra™ ESBL agar medium as a diagnostic tool. The interpretation of results ("Manual, visual") is performed by laboratory personnel, but the "device" itself (the culture medium) provides the observable outcome (colony color and growth) which is then interpreted. So, in essence, it's a standalone diagnostic performance assessment of the medium.
7. The Type of Ground Truth Used:
The ground truth was established by a laboratory-based reference method, which included:
- Growth on MacConkey agar with a 10µg cefpodoxime disk.
- Selection of colonies from within the zone of inhibition.
- Biochemical identification.
- Disk diffusion phenotypic confirmatory antimicrobial susceptibility testing for ESBLs as outlined in the Clinical and Laboratory Standards Institute document M100-S23.
8. The Sample Size for the Training Set:
The document does not mention a specific "training set" in the context of machine learning or AI models. This device is a culture medium, and its development (which would be analogous to a training phase) involves formulation and empirical testing, rather than a data-driven training set in the AI sense. The "Reactivity" and "Reproducibility" studies involve a limited number of isolates (48 confirmed ESBL-producing strains for reactivity; 9 blinded ESBL and Non-ESBL isolates for reproducibility) that could be considered part of the development/validation process.
9. How the Ground Truth for the Training Set Was Established:
As there is no "training set" in the AI sense, this question is not directly applicable. For the isolates used in "Reactivity" and "Reproducibility" studies, their ESBL status was "confirmed" (for reactivity) and "expected" (for reproducibility), implying that a definitive laboratory method was used to classify them prior to testing with the Spectra™ ESBL. This would likely follow similar gold standard methods as the clinical study's ground truth.
§ 866.1700 Culture medium for antimicrobial susceptibility tests.
(a)
Identification. A culture medium for antimicrobial susceptibility tests is a device intended for medical purposes that consists of any medium capable of supporting the growth of many of the bacterial pathogens that are subject to antimicrobial susceptibility tests. The medium should be free of components known to be antagonistic to the common agents for which susceptibility tests are performed in the treatment of disease.(b)
Classification. Class II (performance standards).