VITEK 2 AST-Gram Negative Omadacycline (<=0.25 - >=16 µg/mL)

• K Number: K213931
• Device Name: VITEK 2 AST-Gram Negative Omadacycline (<=0.25 - >=16 µg/mL)
• Manufacturer: bioMerieux, Inc.
• Date Cleared: 2022-06-03 ( 169 days)
• Product Code: LON , LTT , LTW
• Regulation Number: 866.1645
• Type: Traditional
• Panel: MI
• Reference & Predicate Devices: K191766

Intended Use

VITEK® 2 AST-Gram Negative Omadacycline is designed for antimicrobial susceptibility testing of Gram negative bacilli and is intended for use with the VITEK® 2 and VITEK® 2 Compact Systems as a laboratory aid in the determination of in vitro susceptibility to antimicrobial agents. VITEK® 2 AST-Gram Negative Omadacycline in is a quantitative test. Omadacycline has been shown to be active against most strains of the microorganisms listed below, according to the FDA label for this antimicrobial.

Active in vitro and in clinical infections:
For Acute Bacterial Skin and Skin Structure Infections (ABSSSI): Enterobacter cloacae Klebsiella pneumoniae For Community Acquired Bacterial Pneumonia (CABP): Klebsiella pneumoniae

The VITEK® 2 Gram-Negative Susceptibility Card is intended for use with the VITEK® 2 Systems in clinical laboratories as an in vitro test to determine the susceptibility of clinically significant aerobic Gram-negative bacilli to antimicrobial agents when used as instructed.

Device Description

The principle of the VITEK®2 AST cards is based on the microdilution minimum inhibitory concentration (MIC) technique reported by MacLowry and Marsh() and Gerlach(0). The VITEK® 2 AST card is essentially a miniaturized, abbreviated and automated version of the doubling dilution technique(3). Each VITEK® 2 AST card contains 64 wells. A control well which only contains microbiological culture media is resident on all cards. The remaining wells contain premeasured portions of a specific antibiotic combined with culture media. The bacterial or yeast isolate to be tested is diluted to a standardized concentration with 0.45 - 0.5% saline before being used to rehydrate the antimicrobial medium within the card. The VITEK® 2 System automatically fills, seals and places the card into the incubator/reader. The VITEK® 2 Compact has a manual filling, sealing and loading operation. The VITEK® 2 Systems monitor the growth of each well in the card over a defined period of time. At the completion of the incubation cycle, a report is generated that contains the MIC value along with the interpretive category result for each antibiotic contained on the card.

VITEK® 2 AST-GN Omadacycline (≤0.25 - >16 µg/mL) has the following concentrations in the card: 0.5, 2. 8 and 16 ug/mL (equivalent standard method concentration by efficacy in us/mL).

AI/ML Overview

This document describes the VITEK® 2 AST-Gram Negative Omadacycline device, an automated antimicrobial susceptibility testing system. The information provided outlines the device's performance against established acceptance criteria, focusing on its ability to accurately determine the susceptibility of Gram-negative bacilli to Omadacycline.

Here's an analysis of the provided information concerning acceptance criteria and supporting studies:

1. Table of Acceptance Criteria and Reported Device Performance:

   The provided document presents the performance of the VITEK® 2 AST-GN Omadacycline against specific criteria. Based on the "FDA Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems," the key performance metrics are Essential Agreement (EA) and Category Agreement (CA), along with Very Major Errors (VME), Major Errors (ME), and Minor Errors (mE).

   Metric	Acceptance Criteria (as per FDA Guidance for AST Systems)	Reported Device Performance (Omadacycline) - ABSSSI (E. cloacae, K. pneumoniae)	Reported Device Performance (Omadacycline) - CABP (K. pneumoniae)
   Essential Agreement (EA) %	≥ 90% for drug/organism combinations	97.9% (410/419)	98.0% (342/349)
   Category Agreement (CA) %	≥ 90% for drug/organism combinations	94.3% (395/419)	93.7% (327/349)
   Very Major Errors (VME) %	≤ 1.5% and ≤ 3 VMEs	2.0% (1/51)	2.7% (1/37)
   Major Errors (ME) %	≤ 3.0% and ≤ 3 MEs	0.0% (0/343)	0.0% (0/290)
   Minor Errors (mE) %	≤ 10.0%	5.5% (23/419)	6.0% (21/349)

   Note: The VME percentages of 2.0% and 2.7% are above the typical acceptance criterion of ≤ 1.5%. However, the absolute number of VMEs is 1 in both cases, which might be considered acceptable depending on the specific interpretation of "and ≤ 3 VMEs" in the guidance document for small sample sizes of resistant isolates. The document explicitly states the device "demonstrated acceptable performance."

2. Sample Size Used for the Test Set and Data Provenance:

   • Test Set Sample Size:
     • For E. cloacae and K. pneumoniae (ABSSSI): 419 isolates.
     • For K. pneumoniae (CABP): 349 isolates.
   • Data Provenance: The study involved an "external evaluation" conducted with "fresh and stock clinical isolates, as well as a set of challenge strains." The document does not specify the country of origin but implies a clinical laboratory setting. It is likely a retrospective collection of isolates from clinical settings.

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts:

   The document describes the "CLSI broth microdilution reference method" as the ground truth. This is a standardized laboratory method, not reliant on individual expert interpretation. Therefore, there were no "experts" in the sense of human readers establishing ground truth for this device; rather, a consensus reference method was used.

4. Adjudication Method for the Test Set:

   Not applicable. The ground truth was established by the CLSI broth microdilution reference method, which is a quantitative laboratory procedure, not a subjective interpretation requiring adjudication.

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 automated antimicrobial susceptibility testing system, not an AI-assisted diagnostic imaging or interpretation system requiring human-in-the-loop performance measurement or MRMC studies. Its performance is compared to a reference laboratory method, not human readers.

6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done:

   Yes, this was a standalone performance study. The VITEK® 2 AST-GN Omadacycline system's performance (an automated device/algorithm) was evaluated against the CLSI broth microdilution reference method without human interpretation as part of the primary outcome. The system generates an MIC value and interpretive category automatically.

7. The Type of Ground Truth Used:

   The ground truth used was the CLSI broth microdilution reference method, which is a standardized laboratory procedure for determining minimum inhibitory concentrations (MICs) of antimicrobials. This is considered a highly reliable and accepted reference standard in microbiology.

8. The Sample Size for the Training Set:

   The document describes a "Premarket Notification (510[k])" which "presents data in support of VITEK® 2 AST-GN Omadacycline." It mentions "external evaluation" with "fresh and stock clinical isolates, as well as a set of challenge strains." This suggests a validation study, but it does not specify a separate "training set" or its size for the development of the VITEK 2 system's algorithms for omadacycline. The VITEK® 2 system itself is a pre-existing platform, and this submission is for a new antimicrobial agent card. The algorithms for interpreting growth patterns for MIC determination are inherent to the VITEK 2 system's design. The data presented are for validation, not explicit "training."

9. How the Ground Truth for the Training Set Was Established:

   As noted in point 8, a specific "training set" for the Omadacycline card and its ground truth establishment is not explicitly detailed in the provided document. The VITEK® 2 system's underlying interpretive algorithms would have been developed and validated previously using reference methods (like broth microdilution) for various antimicrobials and organisms during the initial development of the VITEK® 2 platform. For new antimicrobial cards, the focus is on validating the new agent's performance against the established reference method as outlined in the provided study.

Regulation Number and Section

§ 866.1645 Fully automated short-term incubation cycle antimicrobial susceptibility system.

(a)
Identification. A fully automated short-term incubation cycle antimicrobial susceptibility system is a device that incorporates concentrations of antimicrobial agents into a system for the purpose of determining in vitro susceptibility of bacterial pathogens isolated from clinical specimens. Test results obtained from short-term (less than 16 hours) incubation are used to determine the antimicrobial agent of choice to treat bacterial diseases.(b)
Classification. Class II (special controls). The special control for this device is FDA's guidance document entitled “Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems; Guidance for Industry and FDA.”