(128 days)
The MicroScan Dried Gram-Negative MIC/Combo Panel is used to determine quantitative and/or qualitative antimicrobial agent susceptibility of colonies grown on solid media of rapidly and facultative anaerobic gram-negative bacilli. After inoculation, panels are incubated for 16 - 20 hours at 35°C +/ - 1°C in a non-CO2 incubator, and read either visually or with MicroScan instrumentation, according to the Package Insert. This particular submission is for the antimicrobial ceftolozane/tazobactam at concentrations of 0.25/4 to 16/4 ug/mL to the test panel.
Ceftolozane/azobactam has been shown to be active both clinically and in vitro against the following organisms: Enterobacter cloacae, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, and Pseudomonas aeruginosa
In vitro data is available for the following organisms, but their clinical significance is unknown: Citrobacter koseri, Morganii, Proteus vulgaris, Providencia retteeri, Providencia stuartii, Serratia liquefaciens, and Serratia marcescens
MicroScan Dried Gram-Neqative MIC/Combo Panels are designed for use in determining quantitative and/or qualitative antimicrobial agent susceptibility of colonies grown on solid media of rapidly growing aerobic and facultative anaerobic gram-negative bacilli.
The antimicrobial susceptibility tests are miniaturizations of the broth dilution susceptibility test that have been diluted in broth and dehydrated. Various antimicrobial agents are diluted in broth to concentrations bridging the range of clinical interest. Panels are rehydrated with water after inoculation with a standardized suspension of the organism. After incubation in a non-CO2 incubator for 16-20 hours, the minimum inhibitory concentration (MIC) for the test organism is read by determining the lowest antimicrobial concentration showing inhibition of growth.
This document describes the premarket notification (510(k)) for the MicroScan Dried Gram-Negative MIC/Combo Panels with Ceftolozane/Tazobactam. Here's a breakdown of the requested information:
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria for the MicroScan Dried Gram-Negative MIC/Combo Panel with Ceftolozane/Tazobactam are based on "Essential Agreement" (EA) with a CLSI frozen Reference Panel. While a specific numerical threshold for "acceptable performance" from the guidance document is not explicitly stated in this summary, it's implied that the achieved 92.8% EA is considered acceptable.
| Acceptance Criteria (from "Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems; Guidance for Industry and FDA") | Reported Device Performance (MicroScan Dried Gram-Negative MIC/Combo Panel with Ceftolozane/Tazobactam) |
|---|---|
| Aspirational Goal: Overall Essential Agreement (EA) of ≥ 90% (based on standard AST guidance for new antimicrobial agents) with a CLSI frozen Reference Panel. | 92.8% Essential Agreement (EA) |
| Acceptable reproducibility and precision for inoculum and instrument testing. | Demonstrated acceptable reproducibility and precision. |
| Acceptable Quality Control results. | Demonstrated acceptable Quality Control results. |
2. Sample Size Used for the Test Set and Data Provenance
The exact sample size (number of isolates) for the test set is not explicitly stated in the provided summary. However, it mentions:
- Data Provenance: The external evaluations were conducted with:
- "fresh, recent and stock Efficacy isolates"
- "stock Challenge strains"
- This suggests a mix of clinical (retrospective or prospective depending on "recent") and curated laboratory strains.
- The country of origin is not specified, but typically, these studies are conducted in the country where the device is being submitted for approval (e.g., USA for FDA submission).
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
This information is not provided in the document. For antimicrobial susceptibility testing, the "ground truth" is typically established by the CLSI frozen Reference Panel, which is itself a standardized and highly quality-controlled method. The "experts" in this context are the trained laboratory personnel performing the reference method, rather than "experts" in specific specialties like radiologists.
4. Adjudication Method for the Test Set
This information is not provided in the document. For AST, adjudication as described (e.g., 2+1) is typically not applicable as the reference method (CLSI frozen panel) is considered the gold standard, and the device's results are compared directly to it. Discrepant results would likely be retested rather than adjudicated by multiple expert readers.
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
A Multi-Reader Multi-Case (MRMC) comparative effectiveness study is not applicable and was not done for this device. This device is an automated in vitro diagnostic for determining antimicrobial susceptibility, not an AI-assisted diagnostic imaging or interpretation tool that assists human readers.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done
Yes, a standalone performance evaluation was completed. The device, MicroScan Dried Gram-Negative MIC/Combo Panels with Ceftolozane/Tazobactam, is an automated system (though it can also be read visually) that performs the susceptibility test independent of human interpretation for the primary results. The performance is assessed by comparing its output (MIC values) directly to the CLSI frozen Reference Panel.
7. The Type of Ground Truth Used
The type of ground truth used is a CLSI frozen Reference Panel. This is a recognized gold standard method for antimicrobial susceptibility testing, providing quantitative Minimum Inhibitory Concentration (MIC) values.
8. The Sample Size for the Training Set
The document does not explicitly mention a "training set" as this is not a machine learning or AI-based diagnostic device in the contemporary sense. The "training" of such a device generally refers to the initial development and optimization of the reagent formulations and reading algorithms (if applicable) against known strains, but the specific sample sizes for such internal development are not typically reported in regulatory summaries like this. The data presented here ("external evaluations") would be considered the validation or test set.
9. How the Ground Truth for the Training Set Was Established
As no explicit "training set" is mentioned in the context of machine learning, this question is not directly applicable. However, the foundational methods for establishing ground truth in AST (whether for development or validation) rely on established microbiological techniques, primarily the broth microdilution method as standardized by the Clinical and Laboratory Standards Institute (CLSI). This involves precise preparation of antimicrobial dilutions and bacterial inoculums, followed by incubation and visual determination of the lowest concentration inhibiting visible growth.
§ 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).