(60 days)
The Cepheid® Xpert MRSA Assay performed on the GeneXpert® Dx System (Xpert MRSA) is a qualitative in vitro diagnostic test designed for rapid detection of methicillinresistant Staphylococcus aureus (MRSA) from nasal swabs in patients at risk for nasal colonization. The test utilizes automated real-time polymerase chain reaction (PCR) to detect MRSA DNA. The Xpert MRSA Assay is intended to aid in the prevention and control of MRSA infections in healthcare settings. The Xpert MRSA Assay is not intended to diagnose MRSA nor to guide or monitor treatment for MRSA infections. Concomitant cultures are necessary only to recover organisms for epidemiological typing or for further susceptibility testing.
The Cepheid Xpert methicillin-resistant Staphylococcus aureus (MRSA) Assay is a rapid, automated DNA test for detecting MRSA directly from nasal swab specimens of patients in a healthcare setting. The Xpert MRSA performs real-time, multiplex polymerase chain reaction (PCR) for detection of DNA after an initial manual sample elution step. In this platform, additional sample preparation, amplification, and real-time detection are all fully automated and completely integrated. The system includes a GeneXpert® System, which consists of an instrument, personal computer, and disposable fluidic cartridges that are designed to complete sample preparation and real-time PCR for detection of MRSA in about 75 minutes. Each instrument contains 2-4 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 Assay includes reagents for the detection of the target MRSA. The primers and probes in the Xpert MRSA Assay detect the presence of the staphylococcal cassette chromosome (SCC) inserted into 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 Assay, based on the provided 510(k) summary:
Acceptance Criteria and Reported Device Performance
The acceptance criteria are implied by the comparison to the reference culture method and the predicate device. The primary performance metrics are Sensitivity and Specificity.
| Acceptance Criterion (Implicit) | Reported Device Performance (Xpert MRSA Assay vs. Reference Culture) |
|---|---|
| Sensitivity comparable to or better than predicate (IDI-MRSA™) | 86.3% (95% CI: 80.9-90.6%) |
| Specificity comparable to or better than predicate (IDI-MRSA™) | 94.9% (95% CI: 93.2-96.3%) |
Note: The predicate device (IDI-MRSA™ Assay) had a reported sensitivity of 83.3% and specificity of 94.4% in the same Cepheid Clinical study using the same reference method. Its package insert (using a different enriched culture method) reported 92.5% sensitivity and 96.4% specificity. The Xpert MRSA Assay met the implicit criterion of performing as well as or better than the predicate in the comparative study.
Study Details
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Sample sizes used for the test set and the data provenance:
- Test Set Sample Size: 1077 eligible subjects (patients).
- Data Provenance: A multi-center prospective investigation study at seven institutions. The document does not explicitly state the country of origin, but given the submission is to the FDA, it is highly likely the study was conducted within the United States.
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Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- The ground truth was established by a centralized laboratory culture testing, which is a laboratory method, not directly dependent on expert interpretation in the same way as, for example, a medical imaging study. The document does not specify the number of laboratory personnel or their specific qualifications, but it implies standard microbiological laboratory practices were followed.
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Adjudication method (e.g., 2+1, 3+1, none) for the test set:
- None in the context of human reader adjudication. The ground truth was established by laboratory culture methods (enriched culture method, and for secondary comparison, direct culture method). Presumptive positive colonies from culture methods were confirmed with a tube coagulase test and Gram stain, which are standard laboratory confirmation procedures.
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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, this was not an MRMC comparative effectiveness study involving human readers with and without AI assistance. This study evaluated an automated diagnostic assay (Xpert MRSA) against a reference culture method and a predicate device (IDI-MRSA™). It assesses the performance of the device itself, not an AI assisting human readers.
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If a standalone (i.e., algorithm only without human-in-the-loop performance) was done:
- Yes, this was essentially a standalone performance study. The Xpert MRSA Assay is an "automated DNA test" where "additional sample preparation, amplification, and real-time detection are all fully automated and completely integrated." The reported performance characteristics (Sensitivity, Specificity, PPV, NPV) are for the assay's output directly compared to the reference standard. While laboratory personnel operate the system, the diagnostic result itself is generated by the instrument/algorithm without human interpretative input beyond loading the sample and reading the final result.
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The type of ground truth used (expert consensus, pathology, outcomes data, etc.):
- The primary ground truth used was the enriched culture method performed at a centralized laboratory, which is considered the "most sensitive culture method" for detecting MRSA from nasal swabs. A secondary comparison was made against a "direct culture method." This is a laboratory-based gold standard.
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The sample size for the training set:
- The document describes a clinical study for validation, not explicitly a separate training set. For analytical sensitivity (Limit of Detection), a study was performed with MRSA cells at seven concentrations (0, 5, 10, 20, 40, 60, and 80 CFU/swab) to determine the LoD. This is an analytical experiment, not a clinical training set in the sense of machine learning algorithms. The commercial assay itself is not described as involving a machine learning model that requires a distinct "training set" of clinical data for its development in the way an AI diagnostic often does.
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How the ground truth for the training set was established:
- This question is less applicable as the device is a nucleic acid amplification test (NAAT) and not a machine learning-based AI device that typically requires a large "training set" of labeled clinical data. The analytical sensitivity (LoD) was established using controlled dilutions of MRSA type II cells to define the assay's detection limit, not a clinical ground truth for a training set.
§ 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).