(63 days)
INTENDED USE: Mueller Hinton II Broth (Cation-Adjusted) with Lysed Horse Blood (MHLHB) is intended for use in broth dilution antimicrobial susceptibility testing of Streptococcus pneumoniae with 11 antimicrobial agents; i.e., cefaclor, cefotaxime, ceftriaxone, cefuroxime, chloramphenicol, ervthromvcin, imipenem, penicillin, tetracycline, trimethoprim/ sulfamethoxazole, and vancomycin, according to the protocol described in the Approved Standard M7-A3, "Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically - Third Edition", dated 12/93, published by the National Committee for Clinical Laboratory Standards (NCCLS).
INDICATIONS FOR USE; Use of BBL® Mueller Hinton II Broth (Cation-Adjusted) with Lysed Horse Blood is indicated when Streptococcus pneumoniae has been isolated in pure culture in the clinical laboratory, and a determination is desired as to whether the organism is susceptible, intermediate, or resistant to selected antimicrobial agents. In cases such as these, broth dilution antimicrobial susceptibility testing may be performed on BBL® Mueller Hinton II Broth (Cation-Adjusted) with Lysed Horse Blood, using cefaclor, cefotaxime, ceftrixone, cefuroxime, chloramphenicol, erythromycin, imipenem, penicillin, tetracycline, trimethoprim/sulfamethoxazole, and vancomycin.
Mueller Hinton II Broth (Cation-Adjusted) with Lysed Horse Blood (MHLHB) is an Antimicrobial Susceptibility Culture Medium used for broth dilution antimicrobial susceptibility testing. It is a liquid medium used in tubes (macrodilution) or microtiter trays. The test involves inoculating serial dilutions of the drug in the medium and examining for the presence of growth after incubation to determine the minimal inhibitory concentration (MIC).
The application describes the acceptance criteria and study proving the device meets said criteria for the "Mueller Hinton II Broth (Cation-Adjusted) with Lysed Horse Blood" (MHLHB) for antimicrobial susceptibility testing of Streptococcus pneumoniae.
1. Table of Acceptance Criteria and Reported Device Performance:
| Acceptance Criteria Category | Specific Acceptance Criteria | Reported Device Performance (MHLHB) |
|---|---|---|
| Quality Control Strain Testing | 100% of MICs fall within expected MIC ranges (NCCLS M100-S6, Table 3C) | 100% (220/220) of MICs fell within expected MIC ranges for all 11 antimicrobics. |
| Quality Control Strain Testing | Standard deviation for all antimicrobics less than 1 µg/ml | Standard deviation for all antimicrobics was less than 1 µg/ml. |
| Reproducibility (Essential Agreement) | 100% Essential Agreement with NCCLS reference method for Cefaclor, Cefotaxime, Ceftriaxone, Cefuroxime, Chloramphenicol, Erythromycin, Imipenem, Penicillin, Vancomycin. | 100% Essential Agreement for the listed antimicrobials. |
| Reproducibility (Essential Agreement) | 98% Essential Agreement with NCCLS reference method for Tetracycline | 99% Essential Agreement for Tetracycline. |
| Reproducibility (Essential Agreement) | 98% Essential Agreement with NCCLS reference method for Trimethoprim/Sulfamethoxazole | 98% Essential Agreement for Trimethoprim/Sulfamethoxazole. |
2. Sample Sizes and Data Provenance:
- Test Set Sample Size:
- Quality Control Testing: 20 tests with Streptococcus pneumoniae ATCC 49619 using microtiter panels containing 11 antimicrobics, performed over 10 test days. This represents 220 individual MIC determinations (20 tests * 11 antimicrobics).
- Reproducibility Studies: Streptococcus pneumoniae ATCC 49619 and 9 additional well-characterized S. pneumoniae strains. Performed 3 times per day for 3 days at two field sites for each of the 11 antimicrobics. The exact total number of MIC determinations for the reproducibility studies is not explicitly stated but can be calculated as: (1 quality control strain + 9 additional strains) * 11 antimicrobics * 3 tests/day * 3 days * 2 sites = 10 * 11 * 9 * 2 = 1980 individual MIC determinations.
- Data Provenance: "In-house" testing was performed for the quality control strain. Reproducibility studies were conducted at "two field sites." The data appears to be prospective, generated specifically for this validation study. The country of origin is not explicitly stated but can be inferred to be the US given the submission to the FDA and reliance on NCCLS standards.
3. Number of Experts and Qualifications:
- Not Applicable. This device is a culture medium for antimicrobial susceptibility testing, which generates quantitative Minimal Inhibitory Concentration (MIC) values. The ground truth (reference method) is based on a standardized laboratory procedure (NCCLS M7-A3) rather than expert interpretation of images or clinical data. Therefore, experts for establishing ground truth in the traditional sense (e.g., radiologists) are not used.
4. Adjudication Method:
- Not Applicable. Adjudication methods like 2+1 or 3+1 are typically used when there's subjective interpretation by multiple human experts. In this study, the "ground truth" and "reference method" are objective laboratory procedures (NCCLS M7-A3) for determining MICs. Discrepancies would be resolved through re-testing or troubleshooting the laboratory procedure, not through expert consensus.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study:
- No. An MRMC study is not applicable as this is a laboratory diagnostic product (culture medium) and not an AI-assisted diagnostic tool that aids human readers in interpreting clinical data. The study focuses on the accuracy and reproducibility of the medium itself compared to a reference standard.
6. Standalone Performance Study (Algorithm Only):
- Yes, effectively. While not an algorithm in the software sense, the "device" (MHLHB medium) is tested in a standalone fashion. Its performance (MIC determination) is evaluated directly against the NCCLS reference method without human interpretive intervention beyond performing the standardized laboratory procedure. The study determines the inherent accuracy and reproducibility of the MHLHB medium in yielding MIC values.
7. Type of Ground Truth Used:
- Reference Method (Standardized Laboratory Procedure). The ground truth for both quality control and reproducibility studies is established by the "NCCLS reference method" as described in NCCLS Document M7-A3, "Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically - Third Edition," and interpretive criteria from NCCLS Supplement M100-S6. This involves performing broth dilution antimicrobial susceptibility testing according to the stipulated protocol, which yields the Minimal Inhibitory Concentration (MIC).
8. Sample Size for the Training Set:
- Not Applicable / Not explicitly stated. This document describes a validation study for a medical device (culture medium), not a machine learning model. Therefore, there isn't a "training set" in the context of AI/ML. The device's formulation and manufacturing process would have been optimized through internal development, but this document focuses on its performance validation against established standards.
9. How the Ground Truth for the Training Set was Established:
- Not Applicable. As there is no "training set" in the AI/ML sense, this question is not relevant to the described device validation.
§ 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).