(41 days)
Antimicrobial susceptibility test discs are used for semi-quantitative susceptibility testing of bacteria by standardized agar diffusion. Cefotaxime/Clavulanic Acid, BBL™ Sensi-Disc™ and Ceftazidime/Clavulanic Acid BBL™ Sensi-Disc™ are intended for use for confirmatory tests for organisms that secrete Extended-spectrum ß-lactamases (ESBL)s as indicated in the Results section of the package insert and indicated below.
Use of Cefotaxime/Clavulanic Acid, BBL™ Sensi-Disc™ and Ceftazidime/Clavulanic Acid BBL ™ Sensi-Disc™ together with Cefotaxime and Ceftazidime susceptibility discs for in vitro agar diffusion susceptibility testing are indicated when there is a need to perform a confirmatory test for ESBLs in Klebsiella spp. and Escherichia coli.
Cefotaxime/Clavulanic Acid and Ceftazidime/Clavulanic Acid susceptibility test discs are prepared by impreanating high quality absorbent paper with accurately determined amounts of Cefotaxime, supplied by Marion Roussel, Inc., Kansas City, MO, and Ceftazidime, supplied by Glaxo Wellcome Operations, Cumbria, UK, respectively. Both discs are also impregnated with specific amounts of Clavulanic Acid supplied by SmithKline Beecham Pharmaceuticals, Piscataway, NJ.
The disks are clearly marked with the agents: CTX/CLA and CAZ/CLA. Cefotaxime/Clavulanic Acid and Ceftazidime/Clavulanic Acid susceptibility test discs are provided in cartridges of 50 disks each and packaged separately.
Agar diffusion methods employing dried filter paper discs impregnated with specific concentrations of antimicrobial agents were developed in the 1940's. In order to eliminate or minimize variability in the testing, Bauer et al. developed a standardized procedure in which Mueller Hinton Agar was selected as the test medium.
Various regulatory agencies and standards-writing organizations subsequently published standardized reference procedures based on the Bauer-Kirby method. Among the earliest and most widely accepted of these standardized procedures were those published by the U. S. Food and Drug Administration (FDA) and the World Health Organization (WHO). The procedure was adopted as a consensus standard by the National Committee for Clinical Laboratory Standards (NCCLS) and is periodically updated. The latest NCCLS documents are M2-A6' (1/97) and M100-S92 (1/99).
Disks containing an antimicrobial agent are applied to the surface of Mueller Hinton Agar plates inoculated with pure cultures of clinical isolates. Following incubation, the plates are examined and the zones of inhibition surrounding the discs are measured and compared with established zone size ranges for the antimicrobial agents in order to determine which is most suitable for use in therapy. The determination as to whether the organism is susceptible (S), intermediate (I), or resistant (R) to an antimicrobial agent is made by comparing zone sizes to the interpretive criteria defined in the tables of NCCLS document M100-S9.
Here's a breakdown of the acceptance criteria and the studies performed for the Cefotaxime/Clavulanic Acid and Ceftazidime/Clavulanic Acid BBL™ Sensi-Discs, based on the provided text:
Acceptance Criteria and Device Performance
| Acceptance Criteria | Reported Device Performance |
|---|---|
| Reproducibility | |
| (across sites, lots, and individuals) | * Multisite/Multilot Reproducibility: "Expected results were obtained in all cases" for zone sizes and differences between single and combination disks. |
- Inter-individual Reproducibility: "All results met the acceptance criteria" for variability between individual tests by the same person and between participants. |
| Performance with NCCLS M100-S9 Challenge Set (Jacoby) | "Expected results were obtained in all cases." |
| Accuracy (Comparison to Laboratory-Prepared Disks for ESBL Confirmation) - Correlation with laboratory disks
- Expected outcomes for genotypic and non-ESBL strains
- Overall performance accuracy (acceptance criteria for this specific accuracy study is implied to be 95% or higher based on the text "Overall performance accuracy was 95% and meets the acceptance criteria as outlined in the study protocol.") | * Correlation: "All production disks results correlated with laboratory disks with 100% equivalency in performance."
- Genotypic/Non-ESBL Strains: "Expected outcomes were met for all of the genotypic and non-ESBL strains."
- Phenotypic Strains: "The phenotypic strains performed as expected with the exception of four K. oxytoca strains. These four strains were not detected as ESBL by the reference or test disks."
- Overall Performance Accuracy: "Overall performance accuracy was 95% and meets the acceptance criteria as outlined in the study protocol."
- QC Testing: "QC testing over the course of the study was acceptable. All expected outcomes were achieved during the screening test." |
Study Details
The provided document describes several performance studies, primarily for validation and comparative equivalence to predicate devices, rather than a single comprehensive clinical trial.
2. Sample sizes used for the test set and the data provenance (e.g., country of origin of the data, retrospective or prospective)
- Reproducibility Studies:
- Multisite/Multilot: Tested with NCCLS recommended negative and positive Quality Control organisms. Performed in triplicate at three test sites for ten days using three lots of disks. Specific number of QC organisms not provided.
- Inter-individual: Ten organism strains of various resistance mechanisms. Three individuals tested the ten strains on three different days in triplicate, using one lot of test disks.
- Jacoby Challenge Set: The study used the Jacoby challenge set of organisms. Specific number of organisms not provided.
- Accuracy Testing: Involved "genotypic and phenotypic ESBL strains and non-ESBL strains." Specific number of strains not provided.
- Data Provenance: Not explicitly stated, but given the context of a 510(k) submission to the US FDA and the mention of NCCLS standards, it's highly probable the studies were conducted in the US. The studies appear to be prospective, laboratory-based performance evaluations.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts
Not applicable. The ground truth for these in vitro diagnostic devices is established by standardized laboratory methods (NCCLS M100-S9) and the inherent biological characteristics of the bacterial strains (e.g., genotypic ESBL producers, phenotypic ESBL characteristics). Human experts were involved in performing the tests and reading the results, but they were not adjudicating a "ground truth" in the sense of subjective interpretation of images or clinical outcomes.
4. Adjudication method (e.g., 2+1, 3+1, none) for the test set
Not applicable for establishing ground truth. The "adjudication" for the in vitro test results is based on objective measurements (zone diameters) and comparison to established interpretive criteria (≥5mm increase for ESBL confirmation). Variability between individuals reading zones was assessed in the inter-individual reproducibility study.
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
Not applicable. This device is an in vitro diagnostic susceptibility disc, not an AI-powered diagnostic tool for human readers. The study focuses on the performance of the physical disk, not on comparative effectiveness for human readers using AI.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done
Yes, in essence. The Sensi-Discs themselves (the "device") are used to generate a physical result (zone of inhibition) that is then interpreted according to standardized criteria. The "performance" being evaluated is the ability of the discs to accurately produce these results and differentiate ESBL-producing organisms according to the NCCLS guidelines. The interpretation of the measured zone sizes is a standardized, objective process, not a subjective human interpretation that would require a "human-in-the-loop" assessment in the way AI applications are often evaluated.
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.)
The ground truth was established by:
- Standardized interpretative criteria: NCCLS M100-S9 document, defining a ≥5mm increase in zone diameter as indicative of ESBL production.
- Known characteristics of organism strains: This includes NCCLS recommended Quality Control organisms, the Jacoby challenge set organisms, and specifically characterized "genotypic and phenotypic ESBL strains and non-ESBL strains." This implies that the true ESBL status for these strains was determined through established laboratory methods (e.g., genetic sequencing for genotypic ESBLs, or other phenotypic gold standards).
8. The sample size for the training set
Not applicable. This device is a physical diagnostic disc used in an in vitro laboratory setting, not a machine learning or AI algorithm that requires a "training set" in the computational sense. The studies described are performance evaluations and validation studies.
9. How the ground truth for the training set was established
Not applicable (as above).
§ 866.1620 Antimicrobial susceptibility test disc.
(a)
Identification. An antimicrobial susceptibility test disc is a device that consists of antimicrobic-impregnated paper discs used to measure by a disc-agar diffusion technique or a disc-broth elution technique the in vitro susceptibility of most clinically important bacterial pathogens to antimicrobial agents. In the disc-agar diffusion technique, bacterial susceptibility is ascertained by directly measuring the magnitude of a zone of bacterial inhibition around the disc on an agar surface. The disc-broth elution technique is associated with an automated rapid susceptibility test system and employs a fluid medium in which susceptibility is ascertained by photometrically measuring changes in bacterial growth resulting when antimicrobial material is eluted from the disc into the fluid medium. Test results are used to determine the antimicrobial agent of choice in the treatment of bacterial diseases.(b)
Classification. Class II (performance standards).