(30 days)
The Cepheid® Xpert® MRSA/SA Blood Culture 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 Staphylococus aureus (MRSA) DNA directly from positive blood cultures. The assay utilizes automated real-time polymerase chain reaction (PCR) for the amplification of MRSA/SA specific DNA targets and fluorogenic target-specific hybridization probes for the real-time detection of the amplified DNA. The assay is performed directly on positive blood culture samples from BD BACTEC™ Plus Aerobic/F, BacT/ALERT® SA (Standard Aerobic) or VersaTREK REDOX 1® (aerobic) blood culture bottles that are determined by Gram Stain as Gram Positive Cocci in Clusters (GPCC) or as Gram Positive Cocci in singles (GPC). The Xpert MRSA/SA Blood Culture test is indicated for use in conjunction with other laboratory tests, such as culture, and clinical data available to the clinician as an aid in the detection of MRSA/SA from positive blood culturing of positive blood cultures is necessary to recover organisms for susceptibility testing or for epidemiological typing. The Cepheid Xpert MRSA/SA Blood Culture test is not intended to monitor treatment for MRSA/SA infections.
The Cepheid Xpert® MRSA/SA Blood Culture test is a rapid, automated DNA test for the simultaneous qualitative detection of MRSA and SA DNA directly from blood culture bottle samples that are detected as positive for microbial growth and shown to contain Gram Positive Cocci by Gram stain. The primers and probes in the Xpert MRSA/SA Blood Culture 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 Probe Check Control (PCC) verifies reagent rehydration, PCR tube filling in the cartridge, probe integrity, and dye stability. The sample for testing with the Xpert MRSA/SA Blood Culture test consists of an aliguot taken from a positive blood culture bottle. Using one of the disposable fixed 50 µL volume transfer pipettes provided with the test kit, an aliquot of the positive blood culture is transferred into a single-use tube of Elution Reagent, also provided with the kit. The Elution Reagent is briefly vortexed and the entire content is transferred to the sample chamber of the disposable fluidic cartridge (the Xpert MRSA/SA Blood Culture cartridge), after which the cartridge is ready to place on the instrument. The assay is performed on the Cepheid GeneXpert Systems, which automate and integrate sample purification, nucleic acid amplification and detection of the target sequences in simple or complex samples using real-time PCR. The systems consist of an instrument, personal computer, and preloaded software for running the tests and viewing the results. The GeneXpert Instrument Systems require the use of single-use disposable cartridges that hold the PCR reagents and host the PCR process. Because the cartridges are self-contained, cross-contamination between samples is minimized. In this platform, additional sample preparation, amplification, and real-time detection are all fullyautomated and completely integrated. The Xpert MRSA/SA Blood Culture test performed on the GeneXpert Instrument Systems provides results in approximately 60 minutes. The GeneXpert Instrument Systems, comprised of the GeneXpert Dx Systems and the GeneXpert Infinity Systems, have 1 to 80 randomly accessible modules, depending upon the instrument, that are each capable of performing separate sample preparation and realtime 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 I-CORE® thermocycler for performing real-time PCR and detection.
This document describes the Xpert MRSA/SA Blood Culture test, a qualitative in vitro diagnostic test for detecting Staphylococcus aureus (SA) and methicillin-resistant Staphylococcus aureus (MRSA) DNA directly from positive blood cultures. The submission is a Special 510(k) to modify the assay definition file (ADF).
Here's an analysis of the provided text for acceptance criteria and study details:
1. A table of acceptance criteria and the reported device performance
The provided document is a 510(k) summary for a Special 510(k) submission, indicating a modification to an existing cleared device (predicate device). For such submissions, the primary "acceptance criterion" is demonstrating substantially equivalent performance to the predicate device, especially considering the specific change made. In this case, the change is to the assay definition file (ADF).
The document explicitly states: "The re-analyses showed the devices were substantially equivalent." This implies that the performance after the ADF update met the previous performance standards or comparable benchmarks. However, the document does not present a table of specific numerical acceptance criteria (e.g., sensitivity, specificity thresholds) or a direct comparison of the reported device performance against those criteria in a quantitative manner for the new device. Instead, it relies on the assertion of substantial equivalence based on re-analysis of existing data.
2. Sample size used for the test set and the data provenance (e.g., country of origin of the data, retrospective or prospective)
The document states: "The updated Assay Definition File with rules-based algorithms and release of new GeneXpert software to support this update have been validated by the re-analyses of the original clinical performance data and a subset of the original analytical performance data, including LoD, inclusivity, exclusivity, potential interfering substances, reproducibility, and precision."
- Sample Size: The document does not specify the sample size used for the re-analysis of the clinical performance data or the subset of analytical performance data. It only refers to "original clinical performance data" and "a subset of the original analytical performance data."
- Data Provenance: The document does not provide information on the country of origin of the data or whether the original data was retrospective or prospective. It only mentions "original clinical performance data," implying data collected during the initial clearance of the predicate device (K130894).
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts (e.g., radiologist with 10 years of experience)
The document does not provide information on the number or qualifications of experts used to establish the ground truth for the testing. Since this is an in vitro diagnostic test for bacterial detection, the ground truth would typically be established by standard microbiological culture and identification methods, which are considered objective laboratory results rather than expert interpretation in the same way a medical image would be.
4. Adjudication method (e.g., 2+1, 3+1, none) for the test set
The document does not specify any adjudication method. This is not typically relevant for in vitro diagnostic tests where ground truth is established through objective laboratory methods (like culture) rather than subjective expert consensus on complex cases.
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 designed for evaluating situations where human readers (e.g., radiologists, pathologists) interpret cases, and the technology aims to assist or replace their interpretation.
This section is not applicable to the Xpert MRSA/SA Blood Culture test. This device is an automated in vitro diagnostic test that directly detects bacterial DNA from blood cultures. It does not involve human "readers" interpreting results in the same way an imaging AI might.
6. If a standalone (i.e. algorithm only without human-in-the loop performance) was done
Yes, the device performs as a standalone algorithm (test kit and instrument system) without human-in-the-loop performance for its primary function of detecting MRSA/SA DNA. The device "utilizes automated real-time polymerase chain reaction (PCR) for the amplification of MRSA/SA specific DNA targets and fluorogenic target-specific hybridization probes for the real-time detection of the amplified DNA." The changes described are to the "Assay Definition File" which contains "rules-based algorithms." This indicates a standalone performance where the algorithm generates the result. While a trained technician initiates the test and reviews the output, the diagnostic decision of positive/negative for MRSA/SA is made by the device's automated analysis.
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.)
The ground truth for such a molecular diagnostic test for bacterial identification is typically established through standard microbiological culture and identification methods, including phenotypic and potentially genotypic characterization of the isolates. This is considered an objective laboratory ground truth, not based on expert consensus, pathology, or outcomes data in the usual sense. The "Indications for Use" mention that "Subculturing of positive blood cultures is necessary to recover organisms for susceptibility testing or for epidemiological typing," which points to culture as the gold standard for definitive identification and further characterization.
8. The sample size for the training set
The document is for a modification (Special 510(k)) to an already cleared device ("predicate device," K130894). The modification is to the "assay definition file (ADF) with rules-based algorithms." It explicitly states that this update was validated by "re-analyses of the original clinical performance data" and "a subset of the original analytical performance data."
This implies that the current submission does not involve a new "training set" for developing a new algorithm from scratch. Instead, it seems the "rules-based algorithms" were modified, and their impact was assessed using existing (original) validation data. Therefore, information about a "training set" for the modified algorithm is not provided as it's likely not applicable in the context of this specific type of submission.
9. How the ground truth for the training set was established
As inferred above (point 8), a new "training set" for the modified algorithm is not explicitly mentioned. If the "rules-based algorithms" were developed using any data, that process is not described. However, given the nature of the device (molecular detection of bacteria), any "training" or optimization data would have relied on a ground truth established by standard microbiological culture and identification methods, similar to the validation data.
§ 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).