(43 days)
Antimicrobial Susceptibility Test Discs are used for semi-quantitative in vitro susceptibility testing by standardized agar diffusion test procedures. Ceftibuten Sensi-Discs® are intended for use in determining the susceptibility of grampositive and gram-negative bacteria, including Streptococcus peuemoniae (penicillin-susceptible strains only), Streptococcus pyrogens, Haemophilus influenzae, (including ß-lactamase-producing strains) and Moraxella catarrhalis (including B-lactamase-producing strains) species to Ceftibuten. Zone sizes used for interpretation of tests, including control organism limits, were determined by the antimicrobic manufacturer, Schering Corporation, and received FDA approval under NDA Nos. 50-685 and 50-686.
Use of BBL® Ceftibuten Sensi-Discs® for in vitro agar diffusion susceptibility testing is indicated when there is a need to defermine the susceptibility of bacteria to Ceftibuten.
Ceftibuten Susceptibility Test Discs are prepared by impregnating high quality paper with accurately determined amounts of Ceftibuten supplied by the manufacturer, Schering Corporation, Kenilworth, New Jersey. Each Ceftibuten disc is clearly marked on both sides with the agent and content. Ceftibuten discs are furnished in cartridges of 50 discs each. Ceftibuten cartridges are packed as either a single cartridge in a single box, or in a package containing ten cartridges.
Agar diffusion methods employing dried filter paper discs impregnated with specific concentrations of antimicrobial agents were developed in the 1940s. 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 requlatory 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-A5 (12/93) and M100-S6 (12/95).
Discs containing a wide variety of antimicrobial agents are applied to the surface of Mueller Hinton Agar plates for Haemophilus Test Medium Agar for H. influenzae or Mueller Hinton Agar with 5% Sheep Blood for S. pneumoniae] 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 individual antimicrobial agents in order to determine the agent(s) most suitable for use in antimicrobial therapy. The determination as to whether the organism in question is susceptible (S), intermediate (I), or resistant (R) to an antimicrobial agent is made by comparing zone sizes to those found in the respective organism tables of National Committee for Clinical Laboratory Standards (NCCLS) Document M2-A5 ("Performance Standards for Antimicrobial Disk Susceptibility tests - Fifth Edition, Approved Standard", 12/93) and of NCCLS Document M100-S6 ("Performance Standards for Antimicrobial Susceptibility Testing", Sixth Informational Supplement, 12/95).
Here's a breakdown of the acceptance criteria and the study information based on the provided text, formatted to address your requests:
1. Table of Acceptance Criteria and Reported Device Performance
The device is an Antimicrobial Susceptibility Test Disc. Its performance is measured by its ability to accurately determine the susceptibility of bacteria to Ceftibuten, compared to established standards.
| Acceptance Criteria (from NCCLS Documents M2-A5 and M100-S6) | Reported Device Performance |
|---|---|
| Zone diameter for Haemophilus influenzae (≥28 mm) | ≥28 mm (Susceptible) |
| For Streptococcus pneumoniae (penicillin-susceptible strains only) | Susceptible |
| Control Organism Limits (MIC range for Haemophilus influenzae ATCC 49274) | 0.25-1.0 µg/mL |
| Interpretation: Susceptible (S), Intermediate (I), or Resistant (R) zones sizes must align with NCCLS organism tables. | The provided text states that the zone sizes for interpretation and control organism limits were determined by the antimicrobic manufacturer, Schering Corporation, and received FDA approval. The document refers to NCCLS standards for interpretation. The performance data section directly references the Schering Corporation product insert for CEDAX® (Ceftibuten) as the source of performance data. The interpretation criteria are based on comparing measured zone sizes to established zone size ranges in NCCLS M2-A5 and M100-S6 documents. |
2. Sample Size Used for the Test Set and Data Provenance
The provided summary for K965159 does not explicitly state the sample size used for the test set specifically for the Sensi-Disc performance evaluation. It refers to the Schering Corporation product insert for CEDAX® (Ceftibuten) for "Performance Data."
- Sample Size for Test Set: Not explicitly stated in the provided document. The Schering product insert, which is referenced, would contain this information.
- Data Provenance: The device's zone sizes and control organism limits were determined by the antimicrobic manufacturer, Schering Corporation. This suggests the data is likely prospective, generated during the development and testing of Ceftibuten itself, and subsequently used to establish the Sensi-Disc's performance. The specific country of origin for the data is not specified beyond "Schering Corporation, Kenilworth, New Jersey," which implies United States origin.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
The document does not specify the number of experts or their qualifications who established the ground truth for the Sensi-Disc test set. It states that "Zone sizes used for interpretation of tests, including control organism limits, were determined by the antimicrobic manufacturer, Schering Corporation, and received FDA approval." This implies that the ground truth was established by microbiological experts employed or consulted by Schering Corporation, and later validated by the FDA during the drug's approval process (NDA Nos. 50-685 and 50-686).
4. Adjudication Method for the Test Set
The document does not describe an adjudication method for the test set. The ground truth appears to be established by the manufacturer and validated by the FDA, rather than through a typical multi-reader adjudication process often seen in imaging studies.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done
No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study is not mentioned or implied in this document. This type of study focuses on comparing human reader performance with and without AI assistance, which is not relevant for an antimicrobial susceptibility test disc.
6. If a Standalone (i.e. algorithm only without human-in-the-loop performance) Was Done
Yes, the testing of the Ceftibuten Sensi-Disc is inherently a standalone performance evaluation. The device itself (the disc) yields a zone of inhibition, which is then measured and interpreted by a human technician. The "performance data" refers to the accuracy of these zone sizes and their interpretation against established standards (NCCLS documents). There is no "human-in-the-loop" AI or algorithm being evaluated here; it's the performance of the physical diagnostic product.
7. The Type of Ground Truth Used
The ground truth used for this study is based on expert consensus and standardized reference methods. Specifically:
- Standardized procedures: The "Bauer-Kirby method," adopted by the National Committee for Clinical Laboratory Standards (NCCLS) and published in their documents (M2-A5 and M100-S6).
- Manufacturer-determined and FDA-approved zone sizes: The antimicrobic manufacturer (Schering Corporation) determined the specific zone sizes and control organism limits for Ceftibuten, which were then approved by the FDA as part of the drug's New Drug Applications.
8. The Sample Size for the Training Set
The document does not explicitly mention a "training set" in the context of the Sensi-Disc's development, as it's a diagnostic product rather than an AI/machine learning model that undergoes a distinct training phase.
If we interpret "training set" as the data used to initially establish the interpretation breakpoints for Ceftibuten, this information would reside within the drug's original NDA submission by Schering Corporation. The provided text refers to the "antimicrobic manufacturer, Schering Corporation," having determined these values, but does not give sample sizes.
9. How the Ground Truth for the Training Set Was Established
As above, the concept of a "training set" in the modern AI sense is not directly applicable. However, the ground truth for establishing the interpretive breakpoints (zone sizes for S, I, R) for Ceftibuten was established by:
- Extensive microbiological testing: By Schering Corporation during the drug's development. This would involve testing a large number of bacterial isolates with known Minimum Inhibitory Concentrations (MICs) against Ceftibuten.
- Correlation with clinical outcomes: These in vitro results (MICs and zone sizes) would have been correlated with clinical efficacy data from human trials to establish clinically relevant breakpoints.
- Adherence to standardized methodologies: The testing would have followed established microbiological and pharmaceutical industry standards, likely including methods approved by regulatory bodies like the FDA, and subsequently incorporated into or referenced by NCCLS guidelines.
§ 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).