(260 days)
The KeyPath™ MRSA/MSSA Blood Culture Test - BT is a qualitative in vitro diagnostic test for the timely identification of Staphylococcus aureus (S. aureus) and determination of methicillin susceptibility (MSSA) or methicillin resistance (MRSA) directly from positive blood cultures.
The Test uses bacteriophage amplification to identify the presence of S. aureus and assess the phenotypic response of the target organism to cefoxitin, an indicator of oxacillin (a methicillin analog) resistance.
The assay is performed directly on positive blood culture specimens that are determined as Gram Positive Cocci in singles (GPC) or as Gram Positive Cocci in Clusters (GPCC) by Gram stain.
The KeyPath™ MRSA/MSSA Blood Culture Test - BT is performed directly on positive blood culture specimens from BD BACTEC™ blood culture bottles (Plus Aerobic/F and Plus Anaerobic/F).
The Test is indicated for use in conjunction with other laboratory and clinical data available to the physician as an aid in the detection of MRSA/MSSA from positive blood cultures.
Subculturing of positive blood cultures is necessary for additional susceptibility test determinations, differentiation of mixed growth and for epidemiological typing.
The KeyPath™ MRSA/MSSA Blood Culture Test – BT uses lytic bacteriophage, specific for Staphylococcus aureus, as an amplification technology for detection of S. aureus and determination of methicillin resistance or susceptibility in positive blood cultures. To detect S. aureus (ID Reaction Tube), the bacteriophage infect the S. aureus (if present), replicate within the host (culminating in bacterial lysis) and over the incubation period, produce several cvcles of bacteriophage amplification. In a separate Reaction Tube (RS), the Test uses cefoxitin (an oxacillin and methicillin analog) which inhibits bacteriophage amplification for susceptible organisms (MSSA) and fails to inhibit bacteriophage amplification when the organism is resistant to methicillin (MRSA). The Test then uses a self-performing immunoassay (Detector) to detect the increase in concentration of bacteriophage using antibodies specific to the Test bacteriophage, and calibrated such that at above a threshold concentration, it produces a visible signal.
Here's a breakdown of the acceptance criteria and study details for the MicroPhage KeyPath™ MRSA/MSSA Blood Culture Test - BT, based on the provided document:
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria are not explicitly stated as numerical targets in the document. Instead, the study aims to achieve substantial equivalence to predicate devices and provide robust performance characteristics. The reported device performance is listed below for different analytical measures.
| Acceptance Criteria (Implied) | Reported Device Performance |
|---|---|
| Substantial equivalence to predicate devices (BD GeneOhm StaphSR Assay, Coagulase/Catalase, Remel Staphaurex®, Oxoid PBP2' Latex Agglutination, Cefoxitin Sensi-Disc, Oxacillin Sensi-Disc) | Demonstrated through clinical comparison study outcomes. |
| High Sensitivity for S. aureus detection | 91.8% |
| High Specificity for S. aureus detection | 98.3% |
| High Positive Predictive Value (PPV) for S. aureus detection | 96.3% |
| High Negative Predictive Value (NPV) for S. aureus detection | 96.1% |
| High Category Agreement for methicillin resistance (for S. aureus samples) | 98.9% |
| High Category Agreement for methicillin susceptibility (for S. aureus samples) | 99.4% |
| Low Invalid Rate | 0.3% (all resolved upon retest) |
| Reproducibility | 99.4% reproducible across 3 sites, 2 operators/site, 6 days, 5 strains |
| Inclusivity (detection of diverse S. aureus strains) | Sensitivity 91.8% for S. aureus in a panel of 114 diverse strains |
| Inclusivity (methicillin resistance/susceptibility for diverse S. aureus) | Category agreement 99% for MRSA, 100% for MSSA in inclusivity panel |
| No interference from common substances/conditions | No interference from lipemic, icteric, hemolytic blood; 5 antibiotics, 3 analgesics, antiviral, anticoagulant; RF-positive, HAMA-positive, heterophilic antibody sera; 32 human viruses. |
| Reliable detection in mixed cultures | Reliably detected MRSA in mixed cultures with ~90% (or greater) Gram negative rods/bacilli, non-S. aureus GPC, and Gram positive rods. |
| High Analytical Specificity (non-Staphylococcus aureus isolates) | 98.8% for a panel of 163 isolates (Gram-negative, non-Staphylococci Gram-positive, coagulase-positive Staphylococci, coagulase-negative Staphylococci, yeast) |
| Agreement with mecA-positive/phenotypic MSSA strains | All 28 mecA-positive/phenotypic MSSA strains determined as MSSA by KeyPath™ Test. |
2. Sample Size Used for the Test Set and Data Provenance
- Test Set Sample Size: 1116 paired samples (366 S. aureus).
- Data Provenance: The study was a prospective clinical trial conducted across four clinical sites. The country of origin of the data is not explicitly stated, but given the FDA 510(k) submission, it is typically from the United States or an equivalent regulatory region.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
The document does not specify the number of experts directly, nor their specific qualifications. However, the "standard methods" used to establish ground truth imply the involvement of trained laboratory personnel. These methods include:
- Standard culture identification for S. aureus (Catalase positive, Tube Coagulase positive, Remel Staphaurex® positive).
- Antimicrobial susceptibility determination using 30 µg cefoxitin disk diffusion in accordance with CLSI M100-S19.
This suggests that the ground truth was established by experienced clinical laboratory professionals following established microbiological and susceptibility testing guidelines.
4. Adjudication Method for the Test Set
The document does not explicitly describe an adjudication method for discrepancies between the KeyPath™ Test results and the "standard methods." It notes that invalid results from the KeyPath™ Test were "resolved upon retest," implying re-evaluation of those specific samples for the KeyPath™ Test, but not a formal adjudication of ground truth discrepancies.
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
No, an MRMC comparative effectiveness study involving human readers and AI assistance was not mentioned or performed for this device. The KeyPath™ MRSA/MSSA Blood Culture Test - BT is a diagnostic test kit involving a visual interpretation from a lateral flow immunoassay, not an AI-powered image analysis or diagnostic assist tool for human readers.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done
Yes, the study primarily assesses the standalone performance of the KeyPath™ MRSA/MSSA Blood Culture Test - BT device as a diagnostic test. While the interpretation of the lateral flow immunoassay is visual, it's the test kit's performance being evaluated against established gold standards, not a human reader's performance with or without the kit.
7. The Type of Ground Truth Used (Expert Consensus, Pathology, Outcomes Data, etc.)
The ground truth used was a combination of established microbiological culture methods and phenotypic antimicrobial susceptibility testing:
- For S. aureus identification: Catalase test, Tube Coagulase test, and Remel Staphaurex® test.
- For methicillin resistance/susceptibility: 30 µg cefoxitin disk diffusion test, performed according to CLSI M100-S19 guidelines.
This represents a robust and well-accepted gold standard in clinical microbiology.
8. The Sample Size for the Training Set
The document does not explicitly mention a separate "training set" or its size for the KeyPath™ MRSA/MSSA Blood Culture Test - BT. This device is a diagnostic test kit that uses bacteriophage amplification and immunoassay detection, which typically involves wet-lab development and validation rather than machine learning models that require distinct training sets. The "Non-clinical Studies" section describes inclusivity and analytical specificity testing on panels of strains, which could be considered part of the development and refinement process, but not a "training set" in the context of algorithm development.
9. How the Ground Truth for the Training Set Was Established
As no specific "training set" for an algorithm is mentioned, this question is not directly applicable. However, for the panels used in non-clinical studies (e.g., inclusivity, analytical specificity), the ground truth for strain identification and resistance profiles would have been established using comprehensive microbiological techniques and genetic characterization in a laboratory setting. For instance, the "Evaluation of SCCmec Empty Cassette Variants" section mentions "mecA-positive (MRSA) by commercial and laboratory PCR tests but MSSA by phenotypic culture." This indicates that molecular methods (PCR) and traditional culture methods were used to characterize these strains.
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Image /page/0/Picture/0 description: The image shows the handwritten text "K102342" above a logo. The logo is a semi-circular shape with a dark gray section on the left and a lighter gray section on the right. The text appears to be written in black ink on a white background.
MIC ROP H A G E
510(k) Summary
As required by 21 CFR Section 807.92(c).
| Submitted by: | MicroPhage, Inc.2400 Trade Centre AveLongmont, CO 80503 | MAY - 5 2011 |
|---|---|---|
| Phone number: | (303) 652-5049 | |
| Fax number: | (303) 652-5080 | |
| Contact: | Drew Smith, PhD | |
| Date of Preparation: | April 29, 2011 | |
| Device:Trade name: | KeyPathTM MRSA/MSSA Blood Culture Test - BT | |
| Common name: | Bacterial Identification and Antimicrobial Susceptibility Test (ID/AST);KeyPathTM AST; Methicillin-resistant Staphylococcus aureus (MRSA)and Methicillin-sensitive Staphylococcus aureus (MSSA) from positiveblood culture bottles test. | |
| Type of Test: | Bacteriophage amplification, Methicillin-resistantStaphylococcus aureus (MRSA) and Methicillin-sensitive Staphylococcusaureus (MSSA), qualitative | |
| Regulation section: | 866.2050 - Staphylococcal typing bacteriophage | |
| Classification: | I | |
| Product code: | OUS | |
| Panel: | 83 Microbiology |
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MicroPhage KeyPath™ MRSA/MSSA Blood Culture Test - BT: 510(k) Summary
| Predicate Devices: | BD GeneOhm™ StaphSR Assay | |
|---|---|---|
| K851949 | Wellcome (Remel) Staphaurex® ZL30 | |
| K011710 | Oxoid PBP2' Latex Agglutination | |
| (preAmendment) | BBL (BD) cefoxitin 30 µg Sensi-Disc | |
| (preAmendment) | BBL (BD) oxacillin 1 µg Sensi-Disc | |
| (preAmendment) | Coagulase Test (multiple manufacturers) | |
| (preAmendment) | Catalase Test (multiple manufacturers) |
Device Description:
The KeyPath™ MRSA/MSSA Blood Culture Test – BT uses lytic bacteriophage, specific for Staphylococcus aureus, as an amplification technology for detection of S. aureus and determination of methicillin resistance or susceptibility in positive blood cultures. To detect S. aureus (ID Reaction Tube), the bacteriophage infect the S. aureus (if present), replicate within the host (culminating in bacterial lysis) and over the incubation period, produce several cvcles of bacteriophage amplification. In a separate Reaction Tube (RS), the Test uses cefoxitin (an oxacillin and methicillin analog) which inhibits bacteriophage amplification for susceptible organisms (MSSA) and fails to inhibit bacteriophage amplification when the organism is resistant to methicillin (MRSA). The Test then uses a self-performing immunoassay (Detector) to detect the increase in concentration of bacteriophage using antibodies specific to the Test bacteriophage, and calibrated such that at above a threshold concentration, it produces a visible signal.
Device Intended Use:
The KeyPath™ MRSA/MSSA Blood Culture Test – BT is a qualitative in vitro diagnostic test for the timely identification of Staphylococcus aureus (S. aureus) and determination of methicillin susceptibility (MSSA) or methicillin resistance (MRSA) directly from positive blood cultures.
The Test uses bacteriophage amplification to identify the presence of S. aureus and assess the phenotypic response of the target organism to cefoxitin, an indicator of oxacillin (a methicillin analog) resistance.
The assay is performed directly on positive blood culture specimens that are determined as Gram Positive Cocci in singles (GPC) or as Gram Positive Cocci in Clusters (GPCC) by Gram stain.
The KeyPath™ MRSA/MSSA Blood Culture Test – BT is performed directly on positive blood culture specimens from BD BACTEC™ blood culture bottles (Plus Aerobic/F and Plus Anaerobic/F).
The Test is indicated for use in conjunction with other laboratory and clinical data available to the physician as an aid in the detection of MRSA/MSSA from positive blood cultures.
Subculturing of positive blood cultures is necessary for additional susceptibility test determinations, differentiation of mixed growth and for epidemiological typing.
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Substantial Equivalence:
The KeyPath™ MRSA/MSSA Blood Culture Test - BT is substantially equivalent to the BD GeneOhm™ StaphSR Assay (510(k)# K071026). Both assays are indicated for the identification/detection of S. aureus from blood culture positives and both are indicated for determination/detection of MRSA. Though each use different technologies (bacteriophage amplification vs. RT - PCR), and the MicroPhage Test is phenotypic as opposed to genotypic, both perform with high sensitivity and specificity to their intended targets. Table 1 summarizes the major similarities and differences between these two methods.
Table 1 - Similarities and Differences between the KeyPath™ MRSA/MSSA Blood Culture Test - BT and the BD GeneOhm™ StaphSR assay.
| SIMILARITIES | ||
|---|---|---|
| Item | KeyPath™ MRSA/MSSA Blood Culture Test - BT | BD GeneOhm™ StaphSR Assay |
| Intended Use | The KeyPath™ MRSA/MSSA Blood Culture Test - BTis a qualitative in vitro diagnostic test for the timelyidentification of Staphylococcus aureus ( S. aureus ) anddetermination of methicillin susceptibility (MSSA) ormethicillin resistance (MRSA) directly from positiveblood cultures. | The BD GeneOhm™ StaphSRAssay is a qualitative in vitrodiagnostic test for the rapiddetection of Staphylococcusaureus ( SA ) and methicillin-resistant Staphylococcus aureus(MRSA) directly from positiveblood culture. |
| The Test uses bacteriophage amplification to identify thepresence of S. aureus and assess the phenotypic responseof the target organism to cefoxitin, an indicator ofoxacillin (a methicillin analog) resistance. | The assay utilizes polymerase chainreaction (PCR) for the amplificationof specific targets and fluorogenictarget-specific hybridization probesfor the real-time detection of theamplified DNA. | |
| The assay is performed directly on positive bloodculture specimens that are determined as GramPositive Cocci in singles (GPC) or as Gram PositiveCocci in Clusters (GPCC) by Gram stain. | The assay is performed on grampositive cocci, identified by Gramstain, from positive bloodcultures. The BD GeneOhm™StaphSR Assay is not intended tomonitor treatment for MRSA/SAinfections. Subculturing of positiveblood cultures is necessary for | |
| The KeyPath™ MRSA/MSSA Blood Culture Test - BTis performed directly on positive blood culture specimensfrom BD BACTECTM blood culture bottles (PlusAerobic/F and Plus Anaerobic/F). | ||
| The Test is indicated for use in conjunction with otherlaboratory and clinical data available to the physician asan aid in the detection of MRSA/MSSA from positiveblood cultures. | StaphSR Assay is not intended tomonitor treatment for MRSA/SAinfections. Subculturing of positiveblood cultures is necessary for | |
| Subculturing of positive blood cultures is necessary foradditional susceptibility test determinations,differentiation of mixed growth and for epidemiologicaltyping | further susceptibility testing. | |
| Single Use | Yes | Yes |
| Indication forUse | Professional Use | Professional Use |
| Interpretationof results | Visual | Visual |
| Patientpopulation | Clinical patients | Clinical patients |
| Specimen type | Positive blood culture | Positive blood culture |
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| Assay controls | Pos Control 1: MRSA | Pos Control: MRSA |
|---|---|---|
| Pos Control 2: MSSA | Pos Control: SA | |
| Neg Control: NSA | Neg Control: NSA |
| DISSIMILARITIES | ||
|---|---|---|
| Item | KeyPathTM MRSA/MSSA Blood Culture Test - BT | BD GeneOhmTM StaphSR Assay |
| Time to result | 5 hours | 60-75 minutes |
| Mode of action | The test uses bacteriophage amplification with cefoxitin to quickly determine the presence of MRSA and MSSA in positive blood cultures. | The assay utilizes polymerase chain reaction (PCR) for the amplification of specific targets and fluorogenic target-specific hybridization probes for the real-time detection of the amplified DNA. |
| Assay format | Amplification: bacteriophage amplificationDetection: Lateral flow immunoassay with colloidal gold particles with monoclonal antibodies specific to assay bacteriophage. | Amplification: polymerase chain reaction (PCR)Detection: Fluorogenic target-specific hybridization probes of the amplified DNA. |
*Bolded and underlined portions indicates similarities of intended use.
The KeyPath™ MRSA/MSSA Blood Culture Test – BT is substantially equivalent to combined Coagulase and Catalase Test (both pre-amendment). Both Coag/Cat and MicroPhage Tests are indicated for the identification or detection of S. aureus and are phenotypic tests. Table 2 summarizes the major similarities and differences between these two methods.
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Table 2 – Similarities and Differences between the KeyPath™ MRSA/MSSA Blood Culture Test – BT and the Coagulase Tube and Catalase Slide Tests.
| SIMILARITIES | ||
|---|---|---|
| Item | KeyPath™ MRSA/MSSA Blood Culture Test - BT | Coagulase Tube, Catalase Slide Tests (pre-amendment) |
| Intended Use | The KeyPath™ MRSA/MSSA Blood Culture Test - BT is a qualitative in vitro diagnostic test for the timely identification of Staphylococcus aureus (S. aureus) and determination of methicillin susceptibility (MSSA) or methicillin resistance (MRSA) directly from positive blood cultures. The Test uses bacteriophage amplification to identify the presence of S. aureus and assess the phenotypic response of the target organism to cefoxitin, an indicator of oxacillin (a methicillin analog) resistance. The assay is performed directly on positive blood culture specimens that are determined as Gram Positive Cocci in singles (GPC) or as Gram Positive Cocci in Clusters (GPCC) by Gram stain. The KeyPath™ MRSA/MSSA Blood Culture Test - BT is performed directly on positive blood culture specimens from BD BACTECTM blood culture bottles (Plus Aerobic/F and Plus Anaerobic/F). The Test is indicated for use in conjunction with other laboratory and clinical data available to the physician as an aid in the detection of MRSA/MSSA from positive blood cultures. Subculturing of positive blood cultures is necessary for additional susceptibility test determinations, differentiation of mixed growth and for epidemiological typing | The Coagulase Tube and Catalase Slide Tests (multiple manufacturers) are qualitative in vitro diagnostic test for the identification of Staphylococcus aureus (SA) directly from isolated colonies from a positive blood culture. "Positive" results for both catalase and coagulase are indicative of S. aureus. The assays contain rabbit serum with EDTA for Coagulase Test and peroxide (H2O2) for Catalase Test substrates which will react with coagulase and catalase enzymes expressed by S. aureus. A clumping of rabbit serum confirms the presence of coagulase and production of O₂ bubbles confirms the presence of catalase (i.e. both results indicating presence of S. aureus). The assay is performed on gram positive cocci which have been isolated by streaking on culture plates, identified by Gram stain, from positive blood cultures. Further subculturing of positive blood cultures are necessary for susceptibility testing. |
| Single Use | Yes | Yes |
| Indication for Use | Professional Use | Professional Use |
| Interpretation of results | Visual | Visual |
| Patient population | Clinical patients | Clinical patients |
Table 2 – Similarities and Differences between the KeyPath™ MRSA/MSSA Blood Culture Test – BT and Coagulase/Catalase Tests for S. aureus determination.
| DISSIMILARITIES | ||
|---|---|---|
| Item | KeyPathTM MRSA/MSSA Blood CultureTest - BT | Coagulase Tube, CatalaseSlide Tests(pre-amendment) |
| Specimen type | Positive blood culture | Overnight purified plate culture (i.e. isolatedcolonies) originating from a Positive blood |
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| DISSIMILARITIES | ||
|---|---|---|
| Item | KeyPath™ MRSA/MSSA Blood CultureTest - BT | Coagulase Tube, CatalaseSlide Tests(pre-amendment) |
| Time to result | 5 hours | cultureCatalase: 5 minutesCoagulase: 4-24 hours |
| Mode of action | The test uses bacteriophage amplification withcefoxitin to quickly determine the presence ofMRSA and MSSA in positive blood cultures. | The assays contain rabbit serum with EDTAfor the Coagulase Test and peroxide ( $H_2O_2$ )for the Catalase Test, substrates which willreact with coagulase and catalase enzymesexpressed by S. aureus . A clumping of rabbitserum confirms the presence of coagulase andproduction of $O_2$ bubbles confirms thepresence of catalase. Both results indicate thepresence of S. aureus . |
| Assay format | Amplification: bacteriophage amplificationDetection: Lateral flow immunoassay withcolloidal gold particles with monoclonalantibodies specific to assay bacteriophage. | Amplification: noneDetection: Clumping of coagulase substrateand $O_2$ gas production (i.e. bubbles) ofcatalase substrate when metabolized by therespective enzymes. |
*Bolded and underlined portions indicates similarities of intended use.
The KeyPath™ MRSA/MSSA Blood Culture Test – BT is substantially equivalent to Remel Staphaurex® (510(k)# K851949). Both assays are indicated for the identification or detection of S. aureus and are phenotypic tests. Additionally, both use antibody-based detection methods (lateral flow immunoassay vs. latex agglutination). Table 3 summarizes the major similarities and differences between these two methods.
Table 3 - Similarities and Differences between the KeyPath™ MRSA/MSSA Blood Culture Test - BT and Wellcome (Remel) Staphaurex for S. aureus determination.
| SIMILARITIES | ||
|---|---|---|
| Item | KeyPathTM MRSA/MSSA Blood Culture Test – BT | Remel Staphaurex® |
| Intended Use | The KeyPathTM MRSA/MSSA Blood Culture Test - BT is aqualitative in vitro diagnostic test for the timelyidentification of Staphylococcus aureus ( S. aureus ) anddetermination of methicillin susceptibility (MSSA) ormethicillin resistance (MRSA) directly from positive bloodcultures.The Test uses bacteriophage amplification to identify thepresence of S. aureus and assess the phenotypic response ofthe target organism to cefoxitin, an indicator of oxacillin (amethicillin analog) resistance.The assay is performed directly on positive blood culturespecimens that are determined as Gram Positive Cocci insingles (GPC) or as Gram Positive Cocci in Clusters(GPCC) by Gram stain.The KeyPathTM MRSA/MSSA Blood Culture Test - BT isperformed directly on positive blood culture specimensfrom BD BACTECTM blood culture bottles (Plus Aerobic/F | Staphaurex® is a rapid slideagglutination procedure fordifferentiating staphylococciwhich possess clumping factorand/or protein A, particularlyStaphylococcus aureus , fromstaphylococci which possessneither of these factors. |
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| SIMILARITIES | ||
|---|---|---|
| Item | KeyPathTM MRSA/MSSA Blood Culture Test – BTand Plus Anaerobic/F).The Test is indicated for use in conjunction with otherlaboratory and clinical data available to the physician as anaid in the detection of MRSA/MSSA from positive bloodcultures.Subculturing of positive blood cultures is necessary foradditional susceptibility test determinations, differentiationof mixed growth and for epidemiological typing | Remel Staphaurex® |
| Single Use | Yes | Yes |
| Indication forUse | Professional Use | Professional Use |
| Interpretationof results | Visual | Visual |
| Patientpopulations | Clinical patients | Clinical patients |
| Assaycontrols | Pos Control 1: MRSAPos Control 2: MSSANeg Control: NSA | Pos Control: SANeg Control: NSA |
| DISSIMILARITIES | ||
|---|---|---|
| Item | KeyPathTM MRSA/MSSA Blood Culture Test -BT | Remel Staphaurex® |
| Specimen type | Positive blood culture | Overnight Purified Culture(16-24hr) |
| Time to result | 5 hours | 10 - 15 minutes |
| Mode of action | The test uses bacteriophage amplification withcefoxitin to quickly determine the presence ofMRSA and MSSA in positive blood cultures. | The test detects the presence of clumpingfactor and protein A using coated latexparticles which agglutinate in a rapidslide procedure. |
| Assay format | Amplification: bacteriophage amplificationDetection: Lateral flow immunoassay withcolloidal gold particles with monoclonalantibodies specific to assay bacteriophage. | Amplification: noneDetection: Agglutination of latexparticles. |
- Bolded and underlined portions indicates similarities of intended use.
The KeyPath™ MRSA/MSSA Blood Culture Test – BT is substantially equivalent to the Oxoid PBP2' Latex Agglutination test (510(k)# K011710). Both assays are indicated for the determination or identification of MRSA by surrogate markers (bacteriophage amplification vs. penicillin binding protein 2'). Additionally, both use antibody-based detection methods (lateral flow immunoassay vs. latex agglutination) and are phenotypic tests. Table 4 summarizes the major similarities and differences between these two methods.
Table 4 - Similarities and Differences between the KeyPath™ MRSA/MSSA Blood Culture Test - BT and Oxoid PBP2' Latex Agglutination for MRSA determination.
| SIMILARITIES | ||
|---|---|---|
| Item | KeyPathTM MRSA/MSSA Blood Culture Test – BT | Oxoid PBP2' LatexAgglutination Test |
| Intended Use | The KeyPathTM MRSA/MSSA Blood Culture Test – BT is | This test is a rapid latex |
{7}------------------------------------------------
| SIMILARITIES | ||
|---|---|---|
| Item | KeyPathTM MRSA/MSSA Blood Culture Test – BT | Oxoid PBP2' Latex Agglutination Test |
| a qualitative in vitro diagnostic test for the timelyidentification of Staphylococcus aureus ( S. aureus ) anddetermination of methicillin susceptibility (MSSA) ormethicillin resistance (MRSA) directly from positiveblood cultures.The Test uses bacteriophage amplification to identify thepresence of S. aureus and assess the phenotypic responseof the target organism to cefoxitin, an indicator of oxacillin(a methicillin analog) resistance.The assay is performed directly on positive blood culturespecimens that are determined as Gram Positive Cocci insingles (GPC) or as Gram Positive Cocci in Clusters(GPCC) by Gram stain.The KeyPathTM MRSA/MSSA Blood Culture Test – BT isperformed directly on positive blood culture specimensfrom BD BACTECTM blood culture bottles (PlusAerobic/F and Plus Anaerobic/F).The Test is indicated for use in conjunction with otherlaboratory and clinical data available to the physician as anaid in the detection of MRSA/MSSA from positive bloodcultures.Subculturing of positive blood cultures is necessary foradditional susceptibility test determinations, differentiation agglutination assay, detectingPBP2' (also called PBP2a), inisolates of Staphylococcus , as anaid in identifying methicillin-resistant Staphylococcus aureus(MRSA) and methicillin-resistantcoagulase-negative staphylococci. | ||
| Single Use | Yes | Yes |
| Indication forUse | Professional Use | Professional Use |
| Interpretationof results | Visual | Visual |
| Patientpopulations | Clinical patients | Clinical patients |
| Assay controls | Pos Control 1: MRSAPos Control 2: MSSANeg Control: NSA | Pos Control: MRSANeg Control: NSA |
| DISSIMILARITIES | ||
|---|---|---|
| Item | KeyPath™ MRSA/MSSA Blood Culture Test -BT | Oxoid PBP2' Latex AgglutinationTest |
| Specimen | Positive blood culture | Overnight Purified Culture (16 - 24hrs) |
| Time to result | 5 hours | 45 minutes |
| Mode of action | The test uses bacteriophage amplification withcefoxitin to determine the presence of MRSA andMSSA in positive blood cultures. | Latex particles sensitized with amonoclonal antibody against PBP2'specifically react with methicillin-resistant staphylococci to causeagglutination visible to the unaidedeye. |
| Assay format | Amplification: bacteriophage amplificationDetection: lateral flow immunoassay with | Amplification: none |
.
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| DISSIMILARITIES | |||
|---|---|---|---|
| ltem | KevPath "31 MRSA/MSSA Blood Culture Test - | Oxoid PBP2' Latex Agglutination | |
| BT | Test | ||
| colloidal gold particles with monoclonal | Detection: | ||
| antibodies specific to assay bacteriophage. | Agglutination of latex particles | ||
| Controller Company Controller Company Company Company Company Company Company Company Company Company Company Company Company Company Company Company Company Company Company | Company of the country of the country of the county of the county of the county of the county of the county of the county of the county of the county of the county of the couCarlos Carados Cara Cara Cara Cara Cara Cara Cara Cara Cara Cara Cara Cara Cara Cara Cara Cara Cara Cara Cara Cara Cara Cara Cara Cara Cara Cara Cara Cara Cara Cara Cara Cara |
- Bolded and underlined portions indicates similarities of intended use.
The KeyPath™ MRSA/MSSA Blood Culture Test - BT is substantially equivalent to the BD BBL 30 µg cefoxitin Sensi-Disc and BD BBL 1 µg oxacillin Sensi-Disc (both pre-Amendment devices). All three assays are indicated for the phenotypic determination of MRSA. Additionally, all use a viable culture of bacteria (e.g., S. aureus) to guide interpretation of results. though the MicroPhage Test does not require a subculture of the isolate. All methods produce highly sensitive and specific results for their indicated determinations with low rates of major and very major discrepancies. Table 5 summarizes the major similarities and differences between these two methods.
Table 5 - Similarities and Differences between the KeyPath™ MRSA/MSSA Blood Culture Test - BT, the BD BBL 30 ug cefoxitin Sensi-Disc, and the BD BBL 1 ug oxacillin Sensi-Disc for MRSA/MSSA breakpoint determinations.
| SIMILARITIES | |||
|---|---|---|---|
| Item | KeyPathTM MRSA/MSSA Blood CultureTest - BT | BD BBL cefoxitin30 μg Sensi-disc | BD BBL oxacillin1 μg Sensi-disc |
| Intended Use | The KeyPathTM MRSA/MSSA BloodCulture Test - BT is a qualitative in vitrodiagnostic test for the timely identificationof Staphylococcus aureus (S. aureus) anddetermination of methicillinsusceptibility (MSSA) or methicillinresistance (MRSA) directly from positiveblood cultures.The Test uses bacteriophage amplificationto identify the presence of S. aureus andassess the phenotypic response of the targetorganism to cefoxitin, an indicator ofoxacillin (a methicillin analog) resistance.The assay is performed directly on positiveblood culture specimens that aredetermined as Gram Positive Cocci insingles (GPC) or as Gram Positive Cocci inClusters (GPCC) by Gram stain.The KeyPathTM MRSA/MSSA BloodCulture Test - BT is performed directly onpositive blood culture specimens from BDBACTECTM blood culture bottles (PlusAerobic/F and Plus Anaerobic/F).The Test is indicated for use in conjunctionwith other laboratory and clinical dataavailable to the physician as an aid in thedetection of MRSA/MSSA from positiveblood cultures. | These discs are used forsemi-quantitative invitro susceptibilitytesting by the agar discdiffusion test procedureof common, rapidlygrowing and certainfastidious bacterialpathogens. | These discs are used forsemi-quantitative invitro susceptibilitytesting by the agar discdiffusion test procedureof common, rapidlygrowing and certainfastidious bacterialpathogens. |
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| SIMILARITIES | |||
|---|---|---|---|
| Item | KeyPath™ MRSA/MSSA Blood CultureTest - BT | BD BBL cefoxitin30 μg Sensi-disc | BD BBL oxacillin1 μg Sensi-disc |
| Subculturing of positive blood cultures isnecessary for additional susceptibility testdeterminations, differentiation of mixedgrowth and for epidemiological typing | |||
| Single Use | Yes | Yes | Yes |
| Indicationfor Use | Professional Use | Professional Use | Professional Use |
| Interpretation of results | Visual | Visual | Visual |
| Patientpopulations | Clinical patients | Clinical patients | Clinical patients |
| Assaycontrols | Pos Control 1: MRSAPos Control 2: MSSANeg Control: NSA | Pos Control: MRSANeg Control: MSSA | Pos Control: MRSANeg Control: MSSA |
| DISSIMILARITIES | |||
|---|---|---|---|
| Item | KeyPath™ MRSA/MSSA BloodCulture Test - BT | BD BBL cefoxitin 30 µgSensi-disc | BD BBL oxacillin1 µg Sensi-disc |
| Specimen | Positive blood culture | Overnight Culture | Overnight Culture |
| Time to result | 5 hours | 18-24 hours | 18-24 hours |
| Mode of action | The test uses bacteriophageamplification with cefoxitin toquickly determine the presence ofMRSA and MSSA in positive bloodcultures. | Diffusion of antibioticinto lawn of S. aureus. | Diffusion of antibioticinto lawn of S. aureus. |
| Assay format | Amplification: bacteriophageamplificationDetection: lateral flow immunoassaywith colloidal gold particles withmonoclonal antibodies specific toassay bacteriophage. | Amplification: noneDetection:Visual interpretation ofzone of inhibition. | Amplification: noneDetection:Visual interpretation ofzone of inhibition. |
- Bolded and underlined portions indicates similarities of intended use.
Clinical Comparison Study
MicroPhage conducted a prospective clinical trial on the KeyPath™ MRSA/MSSA Blood Culture test - BT to assess the performance characteristics across four clinical sites against culture and predicate methods.
Subjects included individuals with positive blood cultures on a BACTEC™ blood culture system (9000 series or F/X). Samples were included if they were from subjects 18 years of age or older and the sample was tested on the KeyPath™ MRSA/MSSA Blood Culture Test – BT within 24 hours of positive determination on BACTECTM System (i.e. alarm). Aliquots of the blood culture were used to perform a standard culture identification for S. aureus (Catalase positive, Tube Coagulase positive, Remel Staphaurex® positive) and antimicrobial susceptibility determination (30 µg cefoxitin disk diffusion) in accordance with CLSI M100-S19.
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MicroPhage KeyPath™ MRSA/MSSA Blood Culture Test - BT: 510(k) Summary
There were a total of 1116 (366 S. aureus) paired samples tested for MRSA/MSSA by the KevPath™ MRSA/MSSA Blood Culture Test - BT and the standard methods across all study sites.
Sensitivity and specificity of the MRSA/MSSA Blood Culture Test - BT vs. the standard method for detection of S. aureus were 91.8% and 98.3%, respectively. The positive predictive value was 96.3%, and the negative predictive value was 96.1%.
For samples determined to be S. aureus, category agreement with the cefoxitin disk diffusion test was 98.9% for determination of methicillin resistance, and 99.4% for determination of methicillin susceptibility.
The initial invalid rate was 0.3%, and all invalids were resolved upon retest.
No significant differences in performance were observed across sites, or between blood culture bottle types.
No significant effect was observed in the performance of the KeyPath™ Test in the presence or absence of antibiotic or antiviral treatments.
Non-clinical Studies
Reproducibility - The KeyPath™ Test was found to be 99.4% reproducible in 648 runs at three sites (2 operators per site) over 6 days, when tested against 2 MRSA, 2 MSSA and 1 S. epidermidis strains.
Inclusivity - A panel of 114 S. aureus strains representing the phylogenetic diversity of S. aureus was tested in duplicate with the KeyPath™ Test. The panel included representatives of 17 clonal complexes and 46 multilocus sequence types. The sensitivity for detection of S. aureus was 91.8%. Category agreement was 99% for determination of methicillin-resistance and 100% for determination of methicillin-susceptibility.
Interfering substances – The KeyPath™ Test showed no interference when tested against lipemic, icteric and hemolytic blood samples. A panel of 5 antibiotics, 3 analgesics, an antiviral and an anticoagulant was tested and showed no interference. The immunoassay component (the Detector) was tested against a panel of 20 RF-positive, HAMA-positive and heterophilic antibody sera and showed no cross-reaction to any. The Detector was also tested against a panel of 32 human viruses and showed no cross-reaction.
Mixed culture – MRSA could be reliably detected by the KeyPath™ Test in mixed cultures comprised of ~90% (or greater) Gram negative rods and bacilli, Gram positive cocci in clusters (not S. aureus) and Gram positive rods.
Analytical specificity - A panel of 163 isolates comprised of 33 Gram-negative isolates (29 species), 58 Gram-positive not Staphylococci (49 species), 5 coagulase-positive Staphylococci (5 species), 60 coagulase-negative Staphylococci (9 species) and 7 yeast (7 species) was tested and showed 98.8% specificity.
Evaluation of SCCmec Empty Cassette Variants - A panel of 28 strains determined to be mecApositive (MRSA) by commercial and laboratory PCR tests but MSSA by phenotypic culture methods was tested. All 28 strains were determined to be MSSA by the KeyPath™ Test.
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We conclude that the performance of the KeyPath™ MRSA/MSSA Blood Culture Test – BT is substantially equivalent to:
- Coagulase/catalase and Staphaurex® Test for detection of S.aureus from positive 1) BACTECTM blood cultures,
- BD BBL Cefoxitin 30ug and BD BBL Oxacillin 1ug Sensi-disc Tests for determination of 2) MRSA and MSSA from S. aureus positive Bactec™ blood cultures,
- Oxoid PBP2' Latex Agglutination Test for determination of MRSA from S. aureus positive 3) BactecTM blood cultures, and
- BD GeneOhm™ StaphSR Assay for determination of S. aureus and MRSA from positive 4) blood cultures.
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Image /page/12/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a circular seal with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" arranged around the perimeter. Inside the circle is a stylized graphic of a human figure, represented by three curved lines, suggesting a person in motion or flight.
Food and Drug Administration 10903 New Hampshire Avenue Silver Spring, MD 20993
MicroPhage, Inc. c/o Drew Smith, Ph. D. Chief Science Officer 2400 Trade Centre Avenue Longmont, Colorado 80503
- 5 2011 MAY
Re: K102342
Trade/Device Name: MicroPhage MRSA/MSSA Blood Culture Test-BT Regulation Number: 21 CFR 866.2050 Regulation Name: Staphylococcal typing bacteriophage Regulatory Class: Class I Product Code: OUS Dated: May 3, 2011 Received: May 3, 2011
Dear Dr. Smith:
We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may; therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.
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Page 2 - Dr. Drew Smith
Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
If you desire specific advice for your device on our labeling regulation (21 CFR Part 801). please go to
http://www.fda.gov/AboutFDA/CentersOffices/CDRH/CDRHOffices/ucm115809.htm for the Center for Devices and Radiological Health's (CDRH's) Office of Compliance. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to
http://www.fda.gov/MedicalDevices/Safety/ReportalProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.
You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address http://www.fda.gov/MedicalDevices/Resourcesfor You/Industry/default.htm.
Sincerely yours.
Uwe Schilf fw
Sally A. Hojvat, M.Sc., Ph.D. Director Division of Microbiology Devices Office of In vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health
Enclosure
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MicroPhage, Inc. 2400 Trade Centre Ave. Longmont, CO 80503
510(k) Number: Device Name:
K102342 KeyPath™ MRSA/MSSA Blood Culture Test - BT
Indications for Use Statement
The KeyPath 100 MRSA Blood Culture Test - BT is a qualitative in vitro diagnostic test for the timely identification of Staphylococcus aureus (S. aureus) and determination of methicillin susceptibility (MSSA) or methicillin resistance (MRSA) directly from positive blood cultures.
The Test uses bacteriophage amplification to identify the presence of S. aureus and assess the phenotypic response of the target organism to cefoxitin, an indicator of oxacillin (a methicillin analog) resistance.
The assay is performed directly on positive blood culture specimens that are determined as Gram Positive Cocci in singles (GPC) or as Gram Positive Cocci in Clusters (GPCC) by Gram stain.
The KeyPath™ MRSA/MSSA Blood Culture Test - BT is performed directly on positive blood culture specimens from BD BACTEC™ blood culture bottles (Plus Aerobic/F and Plus Anaerobic/F).
The Test is indicated for use in conjunction with other laboratory and clinical data available to the physician as an aid in the detection of MRSA/MSSA from positive blood cultures.
Subculturing of positive blood cultures is necessary for additional susceptibility test determinations, differentiation of mixed growth and for epidemiological typing.
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Concurrence of CDRH, office of Device Evaluation (ODE)
Prescription Use
Over-The-Counter-Use
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Office of In Vitro Diagnostic Device Evaluation and Safety
510(k) K id 2342
§ 866.2050 Staphylococcal typing bacteriophage.
(a)
Identification. A staphylococcal typing bacteriophage is a device consisting of a bacterial virus intended for medical purposes to identify pathogenic staphylococcal bacteria through use of the bacteria's susceptibility to destruction by the virus. Test results are used principally for the collection of epidemiological information.(b)
Classification. Class I (general controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 866.9.