(266 days)
hemoFISH Masterpanel is a qualitative nucleic acid hybridization assay performed directly on blood culture samples identified as positive by a continuous monitoring blood culture system that demonstrates the presence of organisms as determined by Gram stain and is intended for the identification of the following species / families:
Gram-positive: Staphylococcus spp., Staphylococcus aureus, Streptococcus spp.
Gram-negative: Enterobacteriaceae, Escherichia coli, Klebsiella pneumoniae
The hemoFISH Masterpanel is indicated as an aid in the diagnosis of bacteremia and results should be used in conjunction with other clinical and laboratory findings. Positive hemoFISH Masterpanel results do not rule out coinfection with organisms not included in the hemoFISH Masterpanel is not intended to monitor treatment for bacteremia.
Subculturing of positive blood cultures is necessary to recover organisms for susceptibility testing and epidemiological typing, to identify organisms in the blood culture that are not identified by the hemoFISH Masterpanel, and for species determination of Staphylococcus spp., Streptococcus spp., and Enterobacteriaceae that are not identified by the hemoFISH Masterpanel.
The hemoFISH Masterpanel identifies bacteria within 30 minutes directly from positive blood cultures.
The methodology is based on classical fluorescence in-situ hybridization (FISH) combined with the usage of fluorescently labeled molecular beacons.
A solution of fluorescently labeled molecular DNA beacons is dispensed on fixed and perforated cells prepared from a blood culture. The hybridization is carried out at 52°C for 10 minutes. Submerging the slide into a bath containing a stop solution ceases the reaction. Adding a drop of Mounting Medium to each field prevents fading of fluorescence. After applying a cover slip, the slide is ready for examination using fluorescence microscopy.
The hemoFISH Masterpanel is a qualitative nucleic acid hybridization assay designed for the rapid identification of specific bacterial species/families directly from positive blood culture samples. It utilizes fluorescence in-situ hybridization (FISH) with molecular DNA probes.
Here's an analysis of the acceptance criteria and the study proving the device meets them:
1. Acceptance Criteria and Reported Device Performance
The provided document doesn't explicitly list "acceptance criteria" in a separate table with specific numerical thresholds for sensitivity and specificity that the device must meet. Instead, it presents the results of its performance studies, implying that these results are considered acceptable for substantial equivalence.
However, based on the "Performance Characteristics" section, we can infer the de-facto acceptance criteria by examining the reported performance and the overall conclusion of substantial equivalence. The key performance metrics are Sensitivity (Positive Agreement) and Specificity (Negative Agreement) against routine laboratory methods.
Here's a table summarizing the reported device performance, which the FDA implicitly accepted as meeting the criteria for substantial equivalence:
Table 1: Reported Device Performance (Monomicrobial Cultures, Prospective and Spiked Samples Combined)
| Target Agent (Routine Identification) | Reported Sensitivity (Positive Agreement) | 95% CI (Sensitivity) | Reported Specificity (Negative Agreement) | 95% CI (Specificity) |
|---|---|---|---|---|
| S. aureus (74 samples) | 100% (74/74) | 95.1-100% | 99.7% (594/596) | 98.8-99.9% |
| CNS (174 samples) | 96.0% (167/174) | 91.9-98.0% | 99.8% (495/496) | 98.9-100% |
| Strep. (76 samples) | 100% (76/76) | 95.2-100% | 99.7% (592/594) | 98.8-99.9% |
| E. coli (96 samples) | 95.8% (92/96) | 89.8-98.4% | 99.8% (573/574) | 99.0-100% |
| K. pneumoniae (38 samples) | 100% (38/38) | 90.8-100% | 100% (632/632) | 99.4-100% |
| Other Enterobacteriaceae (64 samples) | 96.9% (62/64) | 89.3-99.1% | 99.7% (604/606) | 98.8-99.9% |
| Other (148 samples) | 97.3% (144/148) | 93.3-98.9% | 98.1% (512/522) | 96.5-99.0% |
Note: The numbers in parentheses for each target agent represent the number of samples identified as such by the "Routine Identification" (ground truth).
2. Sample Size and Data Provenance
-
Test Set Sample Size:
- Clinical Studies (Monomicrobial): 609 prospective blood culture bottles + 61 in-house spiked (monomicrobial) blood culture bottles = 670 monomicrobial blood cultures (combined in Table 3).
- Clinical Studies (Polymicrobial): 55 polymicrobial prospective blood culture bottles (analyzed separately in Table 4).
- Analytical Inclusivity: 120 representative reference strains.
- Analytical Specificity: 215 strains representing clinical relevant species and/or species selected based on sequence similarities.
- Limit of Detection (LoD): Not specified for the number of strains, but "≥19/20 replicates (≥95%) were positive at 10^3 CFU/mL" for each tested species.
- Reproducibility: 90 tests per strain (3 slides/strain tested by 2 different operators on 2 x five consecutive days).
-
Data Provenance: The document does not explicitly state the country of origin for the clinical data. It mentions "3 clinical laboratory studies." Given the submitter's location (Düsseldorf, Germany), it's highly probable that the clinical studies were conducted in Germany or Europe, though this is not confirmed. The data appears to be prospective for the main clinical method comparison study, with additional in-house spiked samples (retrospective/controlled laboratory setting).
3. Number of Experts and Qualifications for Ground Truth
The document does not specify the number of experts or their qualifications involved in establishing the ground truth for the clinical test set. The ground truth for the clinical studies was established by "routine laboratory methods" (e.g., culture, biochemical tests, mass spectrometry, or other conventional microbiology methods), which are presumed to be performed by qualified laboratory personnel following established protocols.
4. Adjudication Method for the Test Set
The document does not mention any specific adjudication method (e.g., 2+1, 3+1) for discordant results between the hemoFISH Masterpanel and the routine laboratory methods. The "routine identification" is presented as the reference standard.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
No, a multi-reader multi-case (MRMC) comparative effectiveness study was not conducted. This device is a diagnostic assay, and the performance evaluation focused on its agreement with standard laboratory identification methods, not on how human readers (e.g., clinicians or microbiologists) improve their diagnostic performance with or without AI assistance. The interpretation of the device results is "Visual by fluorescence microscopy" and is a direct output from the assay, not an interpretation by a human of an AI output.
6. Standalone (Algorithm Only) Performance
The study primarily evaluates the standalone performance of the hemoFISH Masterpanel assay. The "visual by fluorescence microscopy" interpretation refers to a direct reading of the assay's output, not an algorithm's output. There isn't an "algorithm only without human-in-the-loop performance" in the typical sense of AI-driven image analysis. The device itself performs the detection (hybridization and fluorescence), and the "visual" part is the human reading the output. This is a traditional IVD, not an AI/ML-driven device in the sense of image interpretation.
7. Type of Ground Truth Used
The primary ground truth used for the clinical studies was "routine identification" based on standard laboratory methods, which typically involve microbial culture and subsequent identification techniques (e.g., Gram stain, biochemical tests, mass spectrometry, gene sequencing).
For analytical studies:
- Analytical Inclusivity/Specificity: Determined using "representative reference strains" with known identities.
- LoD: Spiked blood culture bottles with known reference strains.
8. Sample Size for the Training Set
The document does not specify an explicit "training set" sample size in the context of machine learning. As a traditional IVD (fluorescence in-situ hybridization assay), this device does not typically undergo a "training" phase like an AI/ML model. The design and validation of the probes (the core "method" of the device) are based on molecular biology principles and analytical testing, not iterative learning from a large dataset.
9. How Ground Truth for the Training Set Was Established
Since there is no "training set" in the context of machine learning for this traditional IVD, the concept of establishing ground truth for a training set does not apply. The development of the hemoFISH Masterpanel involved designing specific DNA probes to target ribosomal RNA sequences of the target organisms. The "ground truth" during this development (analogous to a training phase) would have involved:
- Bioinformatics: In silico analysis of ribosomal RNA sequences to design highly specific and inclusive probes.
- Analytical validation: Testing probe performance against a wide range of known bacterial strains (as mentioned in the Analytical Inclusivity and Specificity sections) to confirm their binding specificity and sensitivity. These analytical studies are part of the device development and validation, not a separate "training set" as understood in AI/ML.
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Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002
October 1, 2015
MIACOM DIAGNOSTICS GMBH EVE BLÖMEKE CLINICAL TRIALS & REGULATORY AFFAIRS MANAGER MEROWINGERPLATZ 1A DÜSSELDORF 40225 GERMANY
Re: K150031
Trade/Device Name: Hemofish Masterpanel Regulation Number: 21 CFR 866.2660 Regulation Name: Microorganism differentiation and identification device Regulatory Class: I Product Code: JSS, MCS, MCS, MDK Dated: August 28, 2015 Received: August 31, 2015
Dear Ms. Blömeke:
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.
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 Parts 801 and 809); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (OS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
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If you desire specific advice for your device on our labeling regulations (21 CFR Parts 801 and 809), please contact the Division of Industry and Consumer Education 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. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR 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/ReportaProblem/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 Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address
http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.
Sincerely yours,
Ribhi Shawar -S
For Uwe Scherf, M.Sc., Ph.D. Director Division of Microbiology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health
Enclosure
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Indications for Use
510(k) Number (if known) K150031
Device Name hemoFISH Masterpanel
Indications for Use (Describe)
hemoFISH Masterpanel is a qualitative nucleic acid hybridization assay performed directly on blood culture samples identified as positive by a continuous monitoring blood culture system that demonstrates the presence of organisms as determined by Gram stain and is intended for the identification of the following species / families:
| Gram-positive | Gram-negative |
|---|---|
| Staphylococcus spp. | Enterobacteriaceae |
| Staphylococcus aureus | Escherichia coli |
| Streptococcus spp. | Klebsiella pneumoniae |
The hemoFISH Masterpanel is indicated as an aid in the diagnosis of bacteremia and results should be used in conjunction with other clinical and laboratory findings. Positive hemoFISH Masterpanel results do not rule out coinfection with organisms not included in the hemoFISH Masterpanel is not intended to monitor treatment for bacteremia.
Subculturing of positive blood cultures is necessary to recover organisms for susceptibility testing and epidemiological typing, to identify organisms in the blood culture that are not identified by the hemoFISH Masterpanel, and for species determination of Staphylococcus spp., Streptococcus spp., and Enterobacteriaceae that are not identified by the hemoFISH Masterpanel.
| Type of Use (Select one or both, as applicable) |
|---|
| Prescription Use (Part 21 CFR 801 Subpart D) |
| Over-The-Counter Use (21 CFR 801 Subpart C) |
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510(k) Summary
(As Required by 21 CFR 807.92)
Image /page/3/Picture/2 description: The image shows the logo for "miacom diagnostics". The logo consists of a green and blue abstract shape on the left, followed by the text "miacom" in blue, with the registered trademark symbol next to it. Below "miacom" is the word "diagnostics" in a smaller font, also in blue.
1. Submitter:
miacom diagnostics GmbH Merowingerplatz 1a 40225 Düsseldorf Germany Phone: +49 211 3015 5795 Fax: +49 211 2989 143
2. Contact Person:
Eve Blömeke
3. Summary Preparation Date:
September 30, 2015
4. Device Name and Classification:
Generic Name: Blood Culture Identification Kit
Trade Name: hemoFISH Masterpanel
Classification: Class I
- Product Code: JSS Kit, Identification, Enterobacteriaceae MCS - DNA-Probe, Staphylococcus aureus MDK - DNA-Probe, Reagents, Streptococcal
Regulation Numbers: 866.2660, 866.3700, 866.3740
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5. Substantial Equivalence Information:
Predicate device name(s) and predicate 510(k) number:
| Predicate Device Name | 510(k) number |
|---|---|
| ----------------------- | --------------- |
Gram-Negative QuickFISH, AdvanDx, Inc.
Comparison with Predicate:
| Item | miacom Device | Predicate QuickFISH |
|---|---|---|
| Intended UseSpecies | Blood culture identificationStaphylococcus spp.S. aureusStreptococcus spp.EnterobacteriaceaeE. coliK. pneumoniae | SameE. coliK. pneumoniaeP. aeruginosa |
| Technology | Fluorescence in situhybridization (rRNA) | Same |
| Probe type | Self-reporting DNA probeslabeled with green or redfluorophore. | Self-reporting PNA probeslabeled with green or redfluorophore. |
| Sample | Positive Blood culture | Same |
| Interpretation | Visual by fluorescencemicroscopy | Same |
| Controls | Rotating ControlsS. aureus ATCC 9144P. aeruginosa ATCC 10145E. coli ATCC 14948S. agalactiae ATCC 12403K. pneumoniae, ATCC 13883 | Positive ControlE. coliK. pneumoniaeP. aeruginosa |
6. Device Description:
The hemoFISH Masterpanel identifies bacteria within 30 minutes directly from positive blood cultures.
The methodology is based on classical fluorescence in-situ hybridization (FISH) combined with the usage of fluorescently labeled molecular beacons.
A solution of fluorescently labeled molecular DNA beacons is dispensed on fixed and perforated cells prepared from a blood culture. The hybridization is carried out at 52°C for 10 minutes. Submerging the slide into a bath containing a stop solution ceases the reaction. Adding a drop of Mounting Medium to each field prevents fading of fluorescence. After applying a cover slip, the slide is ready for examination using fluorescence microscopy.
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7. Intended use(s):
hemoFISH Masterpanel is a qualitative nucleic acid hybridization assay performed directly on blood culture samples identified as positive by a continuous monitoring blood culture system that demonstrates the presence of organisms as determined by Gram stain and is intended for the identification of the following species / genera / families:
| Gram-positive | Gram-negative |
|---|---|
| Staphylococcus spp. | Enterobacteriaceae |
| Staphylococcus aureus | Escherichia coli |
| Streptococcus spp. | Klebsiella pneumoniae |
The hemoFISH Masterpanel is indicated as an aid in the diagnosis of specific agents of bacteremia and results should be used in conjunction with other clinical and laboratory findings. Positive hemoFISH Masterpanel results do not rule out co-infection with organisms not included in the hemoFISH Masterpanel. The hemoFISH Masterpanel is not intended to monitor treatment for bacteremia.
Subculturing of positive blood cultures is necessary to recover organisms for susceptibility testing and epidemiological typing, to identify organisms in the blood culture that are not identified by the hemoFISH Masterpanel, and for species determination of Staphylococcus spp., Streptococcus spp., and Enterobacteriaceae that are not identified by the hemoFISH Masterpanel.
8. Indication(s) for use:
hemoFISH Masterpanel is indicated as an aid in the diagnosis of bacteremia.
9. Performance Characteristics:
Non-clinical studies
Analytical Inclusivity
The inclusivity of hemoFISH was determined using 120 representative reference strains.
In summary, hemoFISH correctly identified:
- Staphylococci other than S. aureus strains comprising Staphylococcus arlettae, Staphylococcus capitis, Staphylococcus chromogenes, Staphylococcus condiment, Staphylococcus epidermidis, Staphylococcus equorum subsp. equorum. Staphylococcus gallinarum, Staphylococcus haemolyticus, Staphylococcus hominis subsp. hominis, Staphylococcus intermedius, Staphylococcus kloosii,
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Staphylococcus lentus, Staphylococcus luqdunensis, Staphylococcus lutrae, Staphylococcus microti, Staphylococcus pasteuri, Staphylococcus piscifermentans, Staphylococcus pseudointermedius, Staphylococcus pulvereri = vitulinus, Staphylococcus rostri, Staphylococcus saprophyticus, Staphylococcus sciuri, Staphylococcus simiae, Staphylococcus succinus subsp. succinus and Staphylococcus xvlosus:
whereas the following 2 subspecies were identified as S. aureus: Staphylococcus schleiferi subsp. coaqulans Staphylococcus schleiferi subsp. schleiferi
- S. aureus strains ●
- Streptococcus strains comprising Streptococcus agalactiae, . Streptococcus anginosus, Streptococcus australis, Streptococcus bovis, Streptococcus constellatus, Streptococcus dysqalactiae, Streptococcus equi, Streptococcus equinus, Streptococcus gallolyticus, Streptococcus gordonii. Streptococcus infantarius, Streptococcus infantis, Streptococcus mitis, Streptococcus mutans, Streptococcus oralis, Streptococcus parasanguinis, Streptococcus pasteurianus, Streptococcus pneumoniae, Streptococcus porcinus, Streptococcus pseudopneumoniae, Streptococcus pyogenes, Streptococcus sanguinis, Streptococcus suis, Streptococcus urinalis and Streptococcus vestibularis
- Enterobacteriaceae other than E. coli and K. pneumoniae (comprising ● Buttiauxella gaviniae, Cedeceae davisiae, Citrobacter freundii, Citrobacter koseri. Cronobacter muvtiensi. Cronobacter sakazakii. Edwardsiella tarda, Enterobacter aerogenes, Enterobacter asburiae, Enterobacter cancerogenus, Enterobacter cloacae subsp. cloacae, Enterobacter cloacae subsp. dissolvens, Enterobacter gergoviae, Enterobacter hormaechei, Enterobacter/Pluralibacter pyrinus, Escherichia (Shimwella) blattae, Escherichia hermanii, Escherichia vulneris, Ewingella americana, Hafnia alvei, Klebsiella oxytoca, Kluyvera ascorbata, Leclercia adecarboxylata, Morganella morganii, Pantoea (Enterobacter) agglomerans, Plesiomonas shigelloides, Proteus hauseri, Proteus mirabilis, Proteus penneri, Proteus vulgaris, Providencia (Proteus) acalifaciens, Providencia (Proteus) rettgeri, Rahnella aquatilis, Raoultella planticola, Raoultella terrigena, Salmonella abony, Salmonella bongori, Salmonella choleraesuis, Salmonella enterica-heidelberg, Salmonella enterica-paratyphi, Salmonella typhimurium, Salmonella vellore, Serratia fonticola, Serratia liquefaciens, Serratia marcescens, Serratia plymuthica, Serratia proteamaculans and Yokenella regensburgei
{7}------------------------------------------------
whereas the following species were identified as Other: Tatumella ptyseos whereas following species were identified as E. coli: Escherichia albertii Escherichia fergusonii Shigella boydii Shigella flexneri whereas following species were identified as K. pneumoniae: Klebsiella variicola
- Escherichia coli strains .
- Klebsiella pneumoniae strains, incl. subsp. ozaenae and ● rhinoscleromatis
Analytical Specificity
The analytical specificity (exclusivity) of each of the 6 Beacons was determined using 215 strains representing clinical relevant species and/or species selected based on sequence similarities from in silico analysis. False positives results were observed with the following organisms:
Staphylococcus Beacon reacting with Macrococcus caseolyticus.
S. aureus Beacon reacting with Staphylococcus schleiferi subsp. schleiferi, Staphylococcus schleiferi subsp. coagulans and Macrococcus caseolyticus.
E. coli Beacon reacting with Shigella boydii, Shigella flexneri, Escherichia albertii and Escherichia fergusonii.
K. pneumoniae Beacon reacting with K. variicola.
Streptococcus Beacon reacting with Leuconostoc carnosum, Leuconostoc mesenteroides and Lactococcus (Streptococcus) lactis.
Limit of Detection
The limit of detection (LoD) was assessed for each target species by testing blood culture bottles spiked with reference strains of S. epidermidis, S. aureus, S. pneumoniae, S. agalactiae, E. coli, K. pneumoniae, P. mirabilis. For each species, ≥19/20 replicates (≥95%) were positive at 10° CFU/mL.
Reproducibility - Precision & Accuracy
Microscope slides with smears of blood cultures spiked with S. aureus, S. pneumoniae, S. agalactiae, E. faecalis, E. coli, K. pneumoniae, P. aeruginosa, S.
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maltophilia and A. baumanii, respectively, were prepared. The slides (3 slides/strain) were tested by 2 different operators on 2 x five consecutive days in accordance with the hemoFISH procedure for a total of 90 tests per strain.
The Reproducibility Study results are summarized in Table 1 below:
| Organisms/Probe | Failure Rate | Reproducibility |
|---|---|---|
| Staphylococcus | 0% (0/90) | 100% (90/90) |
| 95.9-100% | ||
| S. aureus | 0% (0/90) | 100% (90/90) |
| 95.9-100%99.4% (179/180) | ||
| Streptococcus | 0.6% (1/180) | 96.9-99.9% |
| Enterobacteriaceae0.6% (1/180) | 99.4% (178/179) | |
| 96.6-99.9% | ||
| E. coli | 1.3% (1/90) | 100% (89/89) |
| 95.9-100% | ||
| K. pneumoniae | 0% (0/90) | 98.9% (89/90) |
| 94.0-99.8% | ||
| Other | 0.3% (1/360) | 100% (359/359) |
| 98.9-100% |
Table 1. Reproducibility
In summary. 99.8% (808/810) tests vielded valid test results of which 99.8% (806/808) were correct. The two invalid results with S. maltophilia and E. coli, respectively, were due to positive reaction with the Negative Control. The two incorrect results were: S. agalactiae identified as 'Other' and K. pneumoniae identified as Other Enterobacteriaceae.
Co-infection
Positive blood cultures were prepared with two target organisms that are identified in the same microscope field (S. aureus and E. coli or S. pneumoniae and K. pneumoniae). One organism was inoculated at a level close to the LoD and the other at 10-10° CFU/ml or vice versa. The blood culture vials were incubated until they turned positive and then tested according the hemoFISH procedure.
All assay results were as expected, indicating that the hemoFISH Masterpanel is capable of correctly identifying mixed cultures of E. coli and S. aureus or S. pneumoniae and K. pneumoniae that are detected in the same field when the target levels are above the LoD of the assay.
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Clinical studies
Method comparison of hemoFISH Masterpanel to routine methods
The performance of hemoFISH Masterpanel versus routine laboratory methods was assessed in 3 clinical laboratory studies using a total of 609 monomicrobial and 55 polymicrobial prospective blood culture bottles as well as 61 in-house spiked (monomicrobial) blood culture bottles. The total number of monomicrobial blood cultures that were analyzed was 670. The results from testing the prospective blood cultures are shown in Table 2 and for the prospective and spiked samples combined in Table 3. The polymicrobial cultures were analyzed separately as shown in Table 4. The studies included BACTEC Plus Aerobic/F and Anaerobic/F, and VersaTREK REDOX 1 and 2 blood culture bottles.
| Table 2. Agreement with routine identification for 609 monomicrobial blood | ||||
|---|---|---|---|---|
| cultures (in-house spiked blood cultures excluded) |
| Routine Identification | ||||||||
|---|---|---|---|---|---|---|---|---|
| S. aureus(69) | CNS1(167) | Strep.2(67) | E. coli(94) | K. pneu(36) | Other entero3(41) | Other4(135) | ||
| HemoFISH | S. aureus | 69 | 2 | |||||
| Other Staph | 160 | 1 | ||||||
| Streptococci | 67 | 1 | 1 | |||||
| E. coli | 90 | 1 | ||||||
| K. pneu | 36 | |||||||
| Other entero | 1 | 41 | 1 | |||||
| Other | 5 | 3 | 1315 | |||||
| Sensitivity | 100% | 95.8% | 100% | 95.7% | 100% | 100% | 97.0% | |
| 69/69 | 160/167 | 67/67 | 90/94 | 36/36 | 41/41 | 131/135 | ||
| 95% CI | 94.7- | 91.6- | 94.6- | 89.6- | 90.4- | 91.4- | 92.6- | |
| 100% | 98.0% | 100% | 98.3% | 100% | 100% | 98.8% | ||
| Specificity | 99.6% | 99.8% | 99.6% | 99.8% | 100% | 99.6% | 98.3% | |
| 538/540 | 441/442 | 540/542 | 514/515 | 573/573 | 566/568 | 466/474 | ||
| 95% CI | 98.7- | 98.7- | 98.7- | 98.9- | 99.3- | 98.7- | 96.7- | |
| 99.9% | 100% | 99.9% | 100% | 100% | 99.9% | 99.1% |
"CNS comprises the following members of the coagulase negative staphylococi that were identified to the species level by standard laboratory methods: S. auricularis, S. caprae, S. carnosus, S. epidermidis, S. haemolyticus, S. hominis subsp. novobiosepticus, S. lugdunensis, S. pettenkoferi, S. saccharolyticus, S. simulans, S. warneri
2 Strep. comprises the following members of Streptocoi that were identified to the species level by standard laboratory methods: S. agalactiae, S. alactolyticus, S. anginosus, S. dysgalactiae subsp. equisimilis, S. gallolyticus subsp. pasteurianus, S. gordonii, Streptococcus group G, S. interiensis, S. mitis, S. oralis, S. parasanguinis, S. pneumoniae, S. pyogenes, S. salivarius, S. sanguinis, S. thermophilus, S. vestibularis
3 Other entero comprises the following members of Enterobacteriaceae that were identified to the species level by standard laboratory methods: Enterobacter cloacae Klebsiella oxytoca Proteus Salmonella enterica subso Salmonella enterica subsp. I (enterica) oranienca subsp. I (enterica typhimurium, Salmonella Group B, Seratia marcescens
"Other comprises the following organisms that were identified to the species/genus level by standard laboraphia defectiva, Acinetobacter spp. including A. baumannii, Actinomyces meyeri subsp. naeslundi, Aerooocus, Bacillus sp. including B. cereus, B. circulans, B. megaterium, B. lincheniformis, B. subtilis var. pumilis, B. thuringiensis, Bacteroides caccae, Bacteroides distacilis group), Bacteroides fragilis, Bacteroides thetaiotaomicron, Bacteroides vulgatus. Candida albicans, Clostridium bifermentas, Corynebacterium spp. including C. amvolatum. C. maruchoti. C. xerosis. Enteroccus faecium. Enterooccus galinarum. Enterooccus raffinosus, Elizabethkinqia meninqoseptica. Fusobacterium nucleatum nucleatum. Granulicatella adiacens, Kocura kristinae. Kocuria varians. Kroppenstedia eburnesenteroides. Micrococus Juteus. Moraxella catarrhalis. Pasteurella multocida, Pediococus pentosaceus, Peptostreptococus asaccharolyticus, Propionibaterium sp.
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Pseudomonas aeruginosa, Rothia detocariosa, Stenotrophomonas acidaminiphila, including Propionibacterium acnes. Stenotrophomonas maltophilia.
5 Includes 1 sample that was positive by the reference method for C. albicans. Based on in silico analysis, the expected hemoFISH result with blood cultures that are positive for C. albicans when no bacterial species is "Fail" due to the absence of hybridization of the Eubacterial probe (refer to Interpretation of results).
Table 3. Comparison of hemoFISH results with routine identification for 670 monomicrobial blood cultures (prospective and spiked samples combined) Routine Identification
| S. aureus(74) | CNS¹(174) | Strep.²(76) | E. coli(96) | K. pneu(38) | Otherentero³(64) | Other⁴(148) | ||
|---|---|---|---|---|---|---|---|---|
| HemoFISH | S. aureus | 74 | 2 | |||||
| Other Staph | 167 | 1 | ||||||
| Streptococci | 76 | 1 | 1 | |||||
| E. coli | 92 | 1 | ||||||
| K. pneu | 38 | |||||||
| Other entero | 1 | 62 | 1 | |||||
| Other | 5 | 3 | 2 | 144⁵ | ||||
| Positiveagreement | 100%74/74 | 96.0%167/174 | 100%76/76 | 95.8%92/96 | 100%38/38 | 96.9%62/64 | 97.3%144/148 | |
| 95% CI | 95.1-100% | 91.9-98.0% | 95.2-100% | 89.8-98.4% | 90.8-100% | 89.3-99.1% | 93.3-98.9% | |
| Negativeagreement | 99.7%594/596 | 99.8%495/496 | 99.7%592/594 | 99.8%573/574 | 100%632/632 | 99.7%604/606 | 98.1%512/522 | |
| 95% CI | 98.8-99.9% | 98.9-100% | 98.8-99.9% | 99.0-100% | 99.4-100% | 98.8-99.9% | 96.5-99.0% |
CNS comprises the following members of the coagulase negative staphylococi that were identified to the species level by standard laboratory methods: S. auricularis, S. carrae, S. carnosus, S. epidermidis, S. galinarum, S. hominis, S. hominis subsp. novobiosepticus, S. lugdunensis, S. pettenkoferi, S. simulans, S. warneri, S. xylosus
"Strep. comprises the following members of Streptococi that were identified to the species level by standard laboratory methods: S. acalactiae, S. alactolutious, S. anginosus, S. bovis II, S. duscalactiae subsp, equisimilis, S. galoluticus subsp. pasteurianus, S. gordonii, Streptococcus group G. S. internedius S. mitis. S. mitis. S. mutans. S. oralis. S. prasanguinis. S. preumoniae. S. progenes. S. salivarius. S. sanguinis. S. thermophilus. S. vestibularis
Yother entero comprises the following members of Enterebacteriaceae that were identified to the species by level standard laboratory methods: Citrobacter amalonatious, Citrobacter farmer, Citrobacter freundii, Citrobacter gillenii, Citrobacter koseri, Citrobacter murliniae, Citrobacter rodentium, Citrobacter muytjensi, Enterobacter cloacae, Klebsiella oxytoca, Morqanella morganii, Proteus mirabilis, Providencia stuartii, Salmonella abony, Salmonella enterica subsp. I Enteridis, Salmonella enterica subsp. I (enterica) oranierica subsp. I (enterica) typhimurium, Salmonella Group B, Salmonella vellore. Serratia marcescens. Yersinia enterocolitica
"Other comprises the following organisms that were identified to the species/genus level by standard laboratory methods: Abiotrophia defectiva, Acinetobacter spp. including A. baemolyticus, A. iwoffii, A. junii, Actinomyces meyeri, Actinomyces meyeri subsp. naeslundi, Aerococus, Bacillus spp. including B. coagulans, B. coagulans, B. megaterium, B. Iincheniformis, B. subtilis var. pumilis, B. thuringiensis, Bacteroides caccae, Bacteroides distasonis (fragilis, Bacteroides ovatus, Bacteroides thetaiotaomicron, Bacteroides vulgatus , Candida albicans, Clostridium bifermentas, Coynebacerium spp. including C. amycolatum, C. matruchoti, C. xerosis, Enterococus faecium, Enterococus gallinarum, Enterococcus raffinosus, Elizabethkingia meningoseptica, Fusobacterium nucleatum, Granulicatella adiacens, Kocuria kristinae, Kocuria varians, Kroppenstedtia eburnea, Leuconostoc pseudomesenteroides, Micrococus Iuteus, Moraxella catarrhalis, Pasteurella multocida, Pediococus pentosaceus, Peptostreptococcus asaccharolyticus, Propionibacterium spp. including Propionibacterium acres, Pseudomonas Rothia detocariosa, Stenotrophomonas acidaminiphila, Stenotrophomonas maltophilia.
5 Includes 1 sample that was positive by the reference method for C. albicans. Based on in silico analysis, the expected hemoFISH result with blood cultures that are positive for C. albicans when no bacterial species is "Fail" due to the absence of hybridization of the Eubacterial probe (refer to Interpretation of results).
{11}------------------------------------------------
Table 4. Comparison of hemoFISH results with routine identification for 55 polymicrobial blood cultures
| Routine Identification | ||||||||
|---|---|---|---|---|---|---|---|---|
| S. aureus | CNS | Strep. | E. coli | K. pneu | Otherentero | Other | ||
| S. aureus | 2 | |||||||
| Other Staph | 14 | |||||||
| HSE. Coli K. pneu Other en | Streptococci | 7 | ||||||
| 13 | 2* | |||||||
| 11 | ||||||||
| Other entero | ব | |||||||
| Other | 8 | |||||||
| Negative | 1 | 7* | 1 | 2 | 1 | 10 | 20 |
- 1 blood culture contained a mixture of S. epidermidis and scored false negative for S. epidermidis and misidentified E. faecalis as E. coli.
10. Conclusion:
The hemoFISH Masterpanel has similar intended use and indications and as the predicate QuickFISH kit.
The performance of the hemoFISH Masterpanel is substantially equivalent to that of routine laboratory methods.
§ 866.2660 Microorganism differentiation and identification device.
(a)
Identification. A microorganism differentiation and identification device is a device intended for medical purposes that consists of one or more components, such as differential culture media, biochemical reagents, and paper discs or paper strips impregnated with test reagents, that are usually contained in individual compartments and used to differentiate and identify selected microorganisms. The device aids in the diagnosis of disease.(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 § 866.9.