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The Xpert® MRSA/SA Skin and Soft Tissue Infection test (Xpert MRSA/SA SSTI test) performed on the GeneXpert® Instrument Systems is a qualitative in vitro diagnostic test intended for the detection of Staphylococcus aureus (SA) and methicillin-resistant Staphylococcus aureus (MRSA) from skin and soft tissue infection swabs. The test utilizes automated real-time polymerase chain reaction (PCR) to detect MRSA/SA DNA. The Xpert MRSA/SA SSTI test is indicated for use in conjunction with other laboratory tests, such as microbiology culture, and clinical data available to the clinician as an aid in the detection of MRSA/SA from skin and soft tissue infections. The Xpert MRSA/SA SSTI test is not intended to monitor treatment for MRSA/SA infections. Concomitant cultures for SA and MRSA are necessary to recover organisms for susceptibility testing or epidemiological typing. In a mixed culture containing MRSA/SA and other organisms (e.g., Gram-negative bacilli, yeast), results can be false negative or variable depending on the concentration of MRSA/SA present, particularly if the concentration of MRSA/SA is close to the limit of detection (LoD) of the test.

The Xpert MRSA/SA SSTI (Xpert MRSA/SA Skin and Soft Tissue Infection) test is an automated in vitro diagnostic DNA test for the qualitative, simultaneous detection of Staphylococcus aureus (SA) and methicillin-resistant Staphylococcus aureus (MRSA) directly from skin and soft tissue specimen swabs. The specimen is collected on a double swab, one of which is placed in a tube containing elution reagent. Following brief vortexing, the eluted material is transferred to a different, uniquely labeled sample chamber of a disposable fluidic cartridge (the Xpert MRSA/SA SSTI cartridge).

The test is performed on the GeneXpert® Instrument Systems (comprised of the GeneXpert® Dx System, GeneXpert® System with Touchscreen, and GeneXpert® Infinity System). In the GeneXpert® Instrument Systems, sample preparation, amplification, and real-time detection are all fully automated and completely integrated. The platform requires the use of singleuse disposable cartridges that hold the PCR reagents and host the PCR process. Because the cartridges are self-contained, cross-contamination between samples is minimized.

The user initiates a test from the system user interface of the GeneXpert® Instrument Systems platform and places the cartridge with sample into a GeneXpert® instrument system which performs hands-off real-time, multiplex polymerase chain reaction (PCR) for detection of SA and MRSA DNA.

Depending upon the specific instrument, a GeneXpert® instrument system may contain 1–80 modules, each which are randomly accessible and capable of performing separate sample preparation and real-time PCR tests. Each module contains a syringe drive for dispensing fluids (i.e., the syringe drive activates the plunger that works in concert with the rotary valve in the cartridge to move fluids between chambers), an ultrasonic horn for lysing cells or spores, and a proprietary ICORE® thermocycler for performing real-time PCR and detection.

The Xpert MRSA/SA SSTI test kit includes reagents for the simultaneous detection of the target organisms, SA and MRSA. The primers and probes in the Xpert MRSA/SA SSTI test detect nucleic acid sequences of the staphylococcal protein A (spa), the gene for methicillin/oxacillin resistance (mecA), and staphylococcal cassette chromosome (SCCmec) inserted in the SA chromosomal attB site.

The test includes a sample processing control (SPC) to control for adequate processing of the target bacteria and to monitor the presence of inhibitor(s) in the PCR assay. The SPC also ensures that the PCR conditions (temperature and time) are appropriate for the amplification reaction and that the PCR reagents are functional. The Probe Check Control (PCC) verifies reagent rehydration, PCR tube filling in the cartridge, probe integrity, and dye stability.

The Xpert MRSA/SA SSTI test performed on the GeneXpert® Instrument Systems provides results in approximately 62 minutes.

The provided text is a 510(k) summary for a medical device called Xpert MRSA/SA SSTI. It describes a diagnostic test for Staphylococcus aureus (SA) and methicillin-resistant Staphylococcus aureus (MRSA) from skin and soft tissue infection swabs, performed on the GeneXpert Instrument Systems.

The document does not contain information about the design of a study to prove acceptance criteria using a test set of data with expert ground truth, human reader performance, or multi-reader multi-case studies.

Instead, it details a Special 510(k) submission to modify an already cleared and legally marketed device (Xpert MRSA/SA SSTI, K080837). The specific modification is to include the GeneXpert® Infinity System instruments as a compatible platform for the test.

Therefore, the performance data presented is focused on demonstrating that the performance of the test on the new instrument platform (GeneXpert Infinity) is equivalent to its performance on previously cleared platforms (GeneXpert Dx System, GeneXpert System with Touchscreen). This is a bridging study rather than a primary clinical validation or an AI performance study as implied by many of the questions.

Given this, I cannot answer all your questions as the relevant information is not in the provided text. However, I will answer what is available and clarify what is missing.

Acceptance Criteria and Reported Device Performance

The acceptance criteria here refer to demonstrating equivalent performance of the Xpert MRSA/SA SSTI test when run on the new GeneXpert Infinity System compared to the previously cleared GeneXpert Dx System.

Study Details (Based on available information)

1. Sample size used for the test set and the data provenance:

   • The document mentions "contrived positive (MRSA cells added to negative matrix) and negative (negative matrix only) samples" for functional testing. It does not provide the specific number of samples (sample size) used in these studies.
   • Data Provenance: The data appears to be prospective as it's generated from specific verification studies ("prepared cartridge hold time study and functional testing") conducted for this 510(k) submission. The country of origin is not specified but implicitly North American given the FDA submission.

2. Number of experts used to establish the ground truth for the test set and the qualifications of those experts:

   • This is a molecular diagnostic test, not an AI image analysis device. The "ground truth" for the functional testing would be the known concentration/presence of MRSA/SA cells in the contrived samples. This is established by the assay design and sample preparation, not by expert interpretation.
   • Therefore, this question does not apply to the type of study described.

3. Adjudication method (e.g. 2+1, 3+1, none) for the test set:

   • Not applicable. This relates to expert consensus in interpreting complex data, which is not the ground truth methodology for this type of molecular test. The measurements (Ct values, presence/absence of signal) are quantitative and objective.

4. 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:

   • No, an MRMC study was not done. This is a diagnostic device for detecting specific DNA sequences, not an AI-powered device assisting human readers.

5. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:

   • The device itself (Xpert MRSA/SA SSTI test on the GeneXpert Instrument Systems) is a standalone automated diagnostic test. Its "performance" is the detection of specific DNA sequences. The studies assess the instrument's ability to run the test and yield equivalent results. The "functional testing" mentioned is effectively the standalone performance of the assay on the new instrument.

6. The type of ground truth used (expert consensus, pathology, outcomes data, etc.):

   • The ground truth for the functional testing was contrived samples with known positive and negative status (e.g., negative matrix, or MRSA cells added to negative matrix where the concentration of MRSA/SA is known). This allows for direct assessment of sensitivity and specificity against a known standard.

7. The sample size for the training set:

   • This device is based on real-time PCR technology, not machine learning that requires a "training set" in the conventional sense. The test's probes and primers are designed based on biological knowledge of the target sequences.
   • Therefore, this question does not apply.

8. How the ground truth for the training set was established:

   • Not applicable, as there is no traditional "training set" for this type of diagnostic device.

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The Cepheid Xpert MRSA/SA Skin and Soft Tissues Infection Assay (Xpert MRSA/SA SSTI Assay) performed in the GeneXpert® Dx System is a qualitative in vitro diagnostic test intended for the detection of Staphylococcus aureus (SA) and methicillin-resistant Staphylococcus aureus (MRSA) from skin and soft tissue infection swabs. The test utilizes automated real-time polymerase chain reaction (PCR) to detect MRSA/SA DNA. The Xpert MRSA/SA SSTI Assay is indicated for use in conjunction with other laboratory tests such as microbiology culture, and clinical data available to the clinician as an aid in the detection of MRSA/SA from skin and soft tissue infections. The Xpert MRSA/SA SSTI Assay is not intended to monitor treatment for MRSA/SA infections. Concomitant cultures for SA and MRSA are necessary to recover organisms for susceptibility testing or epidemiological typing. In a mixed culture containing MRSA/SA and other organisms (e.g. Gram negative bacilli, yeast), results can be false negative or variable depending on the concentration of MRSA/SA present, particularly if the concentration of MRSA/SA is close to the LoD of the assay.

The Cepheid Xpert MRSA/SA Skin and Soft Tissue Infection Assay (Xpert MRSA/SA SSTI Assay) is a rapid, automated DNA test for simultaneously detecting MRSA and SA directly from skin and soft tissue specimen is collected on a double swab, which is placed in a tube containing elution reagent. Following brief vortexing, the eluted matcrial and two single-use reagents (Reagent 1 and Reagent 2) that are provided with the assay are transferred to different, uniquely-labeled chambers of the disposable fluidic cartridge (the Xpert MRSA/SA cartridge). The user initiates a test from the system user interface and places the cartridge into the GeneXpert® Dx System instrument platform, which performs hands-off real-time, multiplex polymerase chain reaction (PCR) for detection of DNA. In this platform, additional sample preparation, amplification, and real-time detection are all fully-automated and completely integrated. The GeneXpert® System consists of a GeneXpert instrument, personal computer, and the multi-chambered fluidic cartridges that are designed to complete sample preparation and real-time PCR for detection of MRSA and SA in approximately 50 minutes. Each system has 1 to 16 randomly accessible modules that are each capable of performing separate sample preparation and real-time PCR tests. Each module contains a syringe drive for dispensing fluids, an ultrasonic horn for lysing cells or spores, and a proprietary I-CORE® thermocycler for performing real-time PCR and detection. The Xpert MRSA/SA Assay includes reagents for the simultaneous detection of the target organisms, SA and MRSA. The primers and probes in the Xpert MRSA/SA Assay detect nucleic acid sequences of the staphylococcal protein A (spa), the gene for MecA-Mediated Oxacillin resistance (mecA), and staphylococcal cassette chromosome (SCCmec) inserted in the SA chromosomal attB site. The test includes a sample processing control (SPC) to control for adequate processing of the target bacteria and to monitor the presence of inhibitor(s) in the PCR assay. The Probe Check Control (PCC) verifies reagent rehydration, PCR tube filling in the cartridge, probe integrity, and dye stability.

Here's a breakdown of the acceptance criteria and study details for the Cepheid Xpert MRSA/SA SSTI Assay, based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

The document doesn't explicitly state "acceptance criteria" numerical targets in a table format. Instead, it presents performance data (Positive Percent Agreement (PPA) and Negative Percent Agreement (NPA)) in comparison to a reference culture method. These performance metrics implicitly serve as the acceptance criteria for regulatory approval.

Implicit Acceptance Criteria (Performance Targets) and Reported Device Performance

Note: The document states "The test results showed the Xpert MRSA/SA SSTI to be substantially equivalent to the current standard of care" and explicitly lists performance data, which are interpreted as meeting implicit acceptance criteria for regulatory clearance.

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

• Clinical Test Set Sample Size: A total of 848 specimens were collected from patients.
  • No Antibiotic Use (within 3 weeks): 441 subjects
  • Unknown Antibiotic Use (within 3 weeks): 200 subjects
  • Known Antibiotic Use (within 3 weeks): 207 subjects
• Data Provenance: The study was a multi-site prospective investigation conducted at four US institutions. This means the data was collected specifically for this study in a forward-looking manner, and from within the United States.

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

The document states that the reference culture method involved "confirmation of presumptive positive colonies was performed with catalase, tube coagulase, and Gram stain. MecA-Mediated Oxacillin resistance was tested by disk diffusion test using a 30 µg cefoxitin disk and cutoff of 21/22 mm." This implies standard microbiology laboratory procedures were followed by trained laboratory personnel.

• Number of Experts: Not explicitly stated as a specific number of individual "experts."
• Qualifications of Experts: Implied to be trained microbiologists or clinical laboratory technologists experienced in performing and interpreting standard microbiology culture, identification (catalase, coagulase, Gram stain), and susceptibility testing (cefoxitin disk diffusion). The reference culture was performed at a "centralized laboratory," suggesting specialized expertise.

4. Adjudication Method for the Test Set

The document does not describe a formal adjudication method (like 2+1 or 3+1 consensus) for the ground truth of the clinical test set. The "reference culture" is treated as the definitive ground truth, performed at a centralized laboratory following established protocols. Implicitly, any discrepancies would be resolved by the standard operating procedures of that centralized laboratory, but a multi-reader adjudication process is not detailed.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was Done

No, an MRMC comparative effectiveness study involving human readers with and without AI assistance was not done. This device is an automated in vitro diagnostic test (Nucleic Acid Amplification Test) performed on a GeneXpert Dx System, designed to provide results directly without requiring human interpretation of complex images or data that AI might otherwise augment for human readers. Its comparison is against a reference culture method.

6. If a standalone (i.e. algorithm only without human-in-the loop performance) was done

Yes, a standalone performance study was done. The Xpert MRSA/SA SSTI Assay is an automated system (algorithm only without human interpretation in the loop beyond sample preparation and loading). The "Performance Characteristics" and "Clinical Performance" sections detail the direct comparison of the Xpert MRSA/SA SSTI Assay's results against the reference culture method, making it a standalone evaluation.

7. The Type of Ground Truth Used

The primary ground truth used for the clinical performance study was reference microbiology culture and susceptibility testing. This involved:

• Enrichment in trypticase soy broth.
• Streaking onto plates with and without cefoxitin.
• Sub-culturing presumptive colonies onto blood agar.
• Confirmation of positive colonies with catalase, tube coagulase, and Gram stain for Staphylococcus aureus (SA) identification.
• MecA-Mediated Oxacillin resistance tested by disk diffusion using a 30 µg cefoxitin disk and a cutoff of 21/22 mm for MRSA identification.

8. The Sample Size for the Training Set

The document does not explicitly state a sample size for a "training set" in the context of machine learning (AI). This device is a real-time PCR assay, which is a molecular diagnostic method based on known biological reactions, not typically developed using machine learning algorithms that require distinct training sets.

However, if "training set" is interpreted more broadly as data used for analytical development and optimization, the document mentions extensive analytical studies:

• Analytical Inclusivity Study on CDC Staphylococcus aureus Specimens: 21 MRSA strains and 3 MSSA strains (total 24 strains).
• Analytical Inclusivity Study on Expanded Panel of Staphylococcus aureus Specimens: 121 additional Staphylococcus aureus strains (78 MRSA, 43 SA).
• Evaluation of Empty Cassette Variants: 22 isolates.
• Limit of Detection Studies: Multiple individual isolates (6 MRSA, 3 SA) each tested with 20 replicates at various concentrations.
• Linearity Studies: SA and MRSA isolates tested across ten-fold serial dilutions.
• Cross-reactivity Study: 105 strains (various bacteria and yeast).
• Evaluation of BORSA Strains: 7 BORSA strains.

These analytical tests provide the data and parameters for the assay's design and demonstrate its performance characteristics, which is analogous to the role of a training set for algorithm development, even though it's a traditional molecular test.

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

For the analytical studies (which can be considered analogous to a training/development phase for a molecular assay), the ground truth was established through:

• Confirmed Identification: Using CDC-reported strains, phylogenetically characterized strains, ATCC cultures, and NARSA strains.
• Phenotypic Testing: Catalase, tube coagulase, Gram stain, and cefoxitin disk diffusion (for oxacillin resistance) were used to characterize discrepant results and confirm the identity and resistance profile of isolates.
• Genetic Characterization: PFGE for USA types and SCCmec typing for MRSA strains provided detailed genetic ground truth.
• Known Concentrations: For LoD and linearity studies, bacterial concentrations were carefully quantified (CFU/sample) to establish precise analytical ground truth.

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