K Number
K172412
Manufacturer
Date Cleared
2018-05-01

(264 days)

Product Code
Regulation Number
866.2560
Reference & Predicate Devices
Predicate For
N/A
AI/MLSaMDIVD (In Vitro Diagnostic)TherapeuticDiagnosticis PCCP AuthorizedThirdpartyExpeditedreview
Intended Use

The BacterioScan 216Dx System is a semi-automated, in vitro diagnostic system (consisting of an instrument, software, and disposable Multicuvettes) that analyzes light scattering to measure any bacterial growth directly from urine sample incubated in trypticase soy broth. The BacterioScan 216Dx is for qualitative determination (presumptive positive or presumptive negative) of bacteriuria at a density of ≥5x104 CFU/mL. The BacterioScan 216Dx results are intended for use in conjunction with other clinical and laboratory findings to aid in the diagnosis of Urinary Tract Infections (UTIs).

The 216Dx System is not intended to provide bacteriuria levels, bacterial identification, or differentiation. The system does not distinguish between growth of infecting, colonizing or contaminating bacteria, or if mixed urogenital flora are present. Presumptive positive urine samples must be cultured. Presumptive negative urine samples must be cultured if a low level of bacteriuria is suspected and is clinically relevant. The system also does not detect anaerobic bacteria, fungi/yeasts, fastidious organisms or those associated with sterile pyuria.

Device Description

The BacterioScan 216Dx System is a semi-automated, in vitro diagnostic system (consisting of an instrument, software, and disposable Multicuvettes) that analyzes light scattering to measure any bacterial growth directly from urine sample incubated in trypticase soy broth. The BacterioScan 216Dx is for qualitative determination (presumptive positive or presumptive negative) of bacteriuria at a density of ≥5x104 CFU/mL. The BacterioScan 216Dx results are intended for use in conjunction with other clinical and laboratory findings to aid in the diagnosis of Urinary Tract Infections (UTIs).

The BacterioScan 216Dx System uses laser light scattering to measure turbidity (particle density) of a prepared urine-broth sample during a period of incubation. The system is designed to kinetically capture digital measurements of sample turbidity at very low particle densities. Classification software analyzes these optical signal measurements, and interprets increasing turbidity as bacterial growth. Samples with robust growth during the second half of the test cycle, and/or high turbidity, are reported as "Presumptive Positive" for bacteriuria and/or UTI. Low turbidity samples that do not exhibit growth are classified as "Presumptive Negative".

The user logs into the 216Dx interface and is prompted to associate a patient sample ID with a Multicuvette serial number and well location. The user will then pipette the prepared liquid samples into a Multicuvette. Once the Multicuvette is filled, it is loaded into a 216Dx Instrument. The Multicuvette is then incubated for approximately three (3) hours. During the instrument run, the 216Dx appliance will analyze optical measurements to provide a qualitative determination of the presence or absence of viable bacteria in urine specimens at a cut-off of >5x10 CFU/ml. The Classification algorithm qualitatively assesses a result by analyzing periodic measurements taken throughout this incubation period.

AI/ML Overview

Here's a summary of the acceptance criteria and study details for the BacterioScan 216Dx System, based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria are not explicitly stated as distinct pass/fail thresholds in the document, but rather demonstrated through the reported performance data. The device's performance is presented in terms of sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for detecting bacteriuria at densities ≥5x10⁴ CFU/mL.

Performance MetricAcceptance Criteria (Implied)Reported Device Performance (Primary Analysis: Bacteriuria ≥5x10⁴ CFU/mL)Reported Device Performance (Secondary Analysis: UTI Associated* ≥5x10⁴ CFU/mL)
SensitivityHigh (e.g., above 80-90%)89.1% (95% CI: 86.8%; 91.1%)97.7% (95% CI: 96.2%; 98.6%)
SpecificityModerate to High (e.g., above 70%)74.4% (95% CI: 72.6%; 76.2%)72.0% (95% CI: 70.2%; 73.8%)
PPVModerate (context dependent)55.3% (95% CI: 52.6%; 58.0%)46.8% (95% CI: 44.1%; 49.6%)
NPVHigh (e.g., above 90%)95.1% (95% CI: 93.9%; 96.0%)99.2% (95% CI: 98.7%; 99.5%)
Reproducibility≥95% for High and Moderate Densities91.7-100% across operators/sites/days for High/Moderate densities; 96.5% for negativesN/A
Limit of Detection (LoD)Approximately equivalent to clinical cut-off (10⁴ CFU/mL)LoD for most common and rare UTI pathogens confirmed to be approximately equivalent to 10⁴ CFU/mL. Some pathogens showed higher LoD and were noted in limitations.N/A

*Limited to bacterial pathogens encountered in the clinical studies.

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

  • Sample Size for Test Set (Method Comparison Study):
    • Overall: 3,153 urine samples enrolled, with 3,052 evaluable specimens for primary analysis of bacteriuria (≥5x10⁴ CFU/mL).
    • For secondary analysis (UTI Associated*), 3,010 evaluable specimens for ≥5x10⁴ CFU/mL and 3,020 for ≥1x10⁵ CFU/mL.
  • Data Provenance: The method comparison study was conducted at three geographically diverse sites. It involved urine samples "received in the laboratory for routine urine culture," suggesting these were clinical samples. The study design implies a prospective collection of samples for the purpose of the comparison. The country of origin is not explicitly stated, but the FDA documentation implies a US context.

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

The ground truth for the test set was established using "Reference cultures performed simultaneously with 216Dx testing." This involved using 1- and 10μL loops, performing colony count plates in triplicate, and generating a median result. Organisms isolated were identified by MALDI.

The document does not specify:

  • The number of experts.
  • The qualifications of those experts (e.g., microbiologists, medical technologists).

4. Adjudication Method for the Test Set

The ground truth was established by median colony count from triplicate plating, which acts as a form of internal reconciliation/adjudication. There is no mention of external expert adjudication (e.g., 2+1, 3+1).

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study

  • No, a TRADITIONAL MRMC study involving human readers with and without AI assistance was not conducted.
  • Instead, this study compared the device (BacterioScan 216Dx System) directly against a reference culture method, not against human interpretation of diagnostic images or data, nor did it involve human readers using or not using the AI to interpret data.
  • Therefore, an effect size of how much human readers improve with AI vs without AI assistance is not applicable to this study.

6. Standalone Performance

Yes, the method comparison study directly assesses the standalone performance of the BacterioScan 216Dx System (algorithm only without human-in-the-loop performance) against the reference culture method.

7. Type of Ground Truth Used

The ground truth used was microbiological culture with colony count and identification by MALDI, which is a form of pathology/laboratory ground truth.

8. Sample Size for the Training Set

The document does not specify the sample size used for the training set. It focuses on the validation studies (e.g., LoD, linearity, reproducibility, and method comparison). The "Classification software analyzes these optical signal measurements" suggests an algorithm, but details about its development (and thus training data) are not provided in this excerpt.

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

Since the document does not mention the training set size, it also does not detail how the ground truth for any training set was established.

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Image /page/0/Picture/0 description: The image shows the logo of the U.S. Food and Drug Administration (FDA). On the left is the Department of Health & Human Services logo. To the right of that is the FDA logo, which is a blue square with the letters "FDA" in white. To the right of the blue square is the text "U.S. FOOD & DRUG ADMINISTRATION" in blue.

May 1, 2018

BacterioScan, Inc. % Fran White President MDC Associates, LLC. 180 Cabot Street Beverly, Massachusetts 01915

Re: K172412

Trade/Device Name: BacterioScan 216Dx System Regulation Number: 21 CFR 866.2560 Regulation Name: Microbial growth monitor Regulatory Class: Class I Product Code: OBQ Dated: August 7, 2017 Received: August 10, 2017

Dear Fran White:

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 Part 801 and Part 809); medical device 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

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Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

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.

For comprehensive regulatory information about medical devices and radiation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/) and CDRH Learn (http://www.fda.gov/Training/CDRHLearn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (http://www.fda.gov/DICE) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).

Sincerely,

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) K172412

Device Name BacterioScan™ 216Dx™ System

Indications for Use (Describe)

The BacterioScan 216Dx System is a semi-automated, in vitro diagnostic system (consisting of an instrument, software, and disposable Multicuvettes) that analyzes light scattering to measure any bacterial growth directly from urine sample incubated in trypticase soy broth. The BacterioScan 216Dx is for qualitative determination (presumptive positive or presumptive negative) of bacteriuria at a density of ≥5x104 CFU/mL. The BacterioScan 216Dx results are intended for use in conjunction with other clinical and laboratory findings to aid in the diagnosis of Urinary Tract Infections (UTIs),

The 216Dx System is not intended to provide bacterial identification, or differentiation. The system does not distinguish between growth of infecting, colonizing or contaminating bacteria, or if mixed urogenital flora are present. Presumptive positive urine samples must be cultured. Presumptive negative urine samples must be cultured if a low level of bacteriuria is suspected and is clinically relevant. The system also does not detect anaerobic bacteria, fungi/ yeasts, fastidious organisms or those associated with sterile pyuria.

Type of Use (Select one or both, as applicable)
X Prescription Use (Part 21 CFR 801 Subpart D) Over-The-Counter Use (21 CFR 801 Subpart C)

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510(k) SUMMARY

Date of SummaryApril 24, 2018
Product NameBacterioScan™ 216Dx™ System
SponsorBacterioScan, Inc.4041 Forest Park AvenueSt. Louis, MO 63108
CorrespondentMDC Associates, LLCFran White, President180 Cabot StreetBeverly, MA 01915Phone: (978) 705 5011Fax: (800) 498 9121Email: fran@mdcassoc.com

Device Trade or Proprietary Name

BacterioScan™ 216Dx™ System

Common Name

Microbial Growth Monitor System

Product Classification

866.2560 Microbial growth monitor

Classification

Class 1 Product code: QBQ

Substantial Equivalency

Comparison Of New Device With Predicate Device Table 1.

CharacteristicBacterioScan™ 216Dx™ Laser MicrobialGrowth Monitor System(New Device)BACTEC™ 9240 SystemK915796(Predicate Device)
Similarities
Intended UseThe BacterioScan 216Dx System is a semi-automated, in vitro diagnostic system(consisting of an instrument, software, anddisposable Multicuvettes) that analyzes lightscattering to measure any bacterial growthdirectly from urine sample incubated intrypticase soy broth. The BacterioScan216Dx is for qualitative determination(presumptive positive or presumptivenegative) of bacteriuria at a density of$≥5x104$ CFU/mL. The BacterioScan 216Dxresults are intended for use in conjunctionwith other clinical and laboratory findings toThe BACTEC 9240 System (Instrument,Aerobic and Anaerobic F Culture Vials) isintended for the detection of aerobic andanaerobic microorganisms (bacteria andfungi) in clinical cultures of blood using afluorescence -based detection system.
CharacteristicBacterioScan™ 216Dx™ Laser MicrobialGrowth Monitor System(New Device)BACTEC™ 9240 SystemK915796(Predicate Device)
aid in the diagnosis of Urinary TractInfections (UTIs).The 216Dx System is not intended toprovide bacteriuria levels, bacterialidentification, or differentiation. Thesystem does not distinguish betweengrowth of infecting, colonizing orcontaminating bacteria, or if mixedurogenital flora are present. Presumptivepositive urine samples must be cultured.Presumptive negative urine samples mustbe cultured if a low level of bacteriuria issuspected and is clinically relevant. Thesystem also does not detect anaerobicbacteria, fungi/yeasts, fastidious organismsor those associated with sterile pyuria.
SampleDirectSame
Growth MediaLiquidSame
IncubationRequiredSame
TechnologyContinuous monitoring of bacterial growthover a period of time in liquid mediumduring incubationSame
QualitativeOutputPresumptive Positive/Presumptive NegativeSame
Differences
Sample TypeUrineBlood
DetectionTechnologyLaser light scattering analysisFluorescence analysis
SampleProcessing360 μL urine and 2.5 mL trypticase soy broth(TSB) contained in one Multicuvette well5 – 7 mL blood and 40 mL enrichedsoybean-casein digest broth with CO2contained in one culture vial
Incubation TimeApproximately 3 hoursUp to 5 – 7 days for negatives; positivering/signal at any time

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Intended Use

The BacterioScan 216Dx System is a semi-automated, in vitro diagnostic system (consisting of an instrument, software, and disposable Multicuvettes) that analyzes light scattering to measure any bacterial growth directly from urine sample incubated in trypticase soy broth. The BacterioScan 216Dx is for qualitative determination (presumptive positive or presumptive negative) of bacteriuria at a density of ≥5x104 CFU/mL. The BacterioScan 216Dx

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results are intended for use in conjunction with other clinical and laboratory findings to aid in the diagnosis of Urinary Tract Infections (UTIs).

The 216Dx System is not intended to provide bacteriuria levels, bacterial identification, or differentiation. The system does not distinguish between growth of infecting, colonizing or contaminating bacteria, or if mixed urogenital flora are present. Presumptive positive urine samples must be cultured. Presumptive negative urine samples must be cultured if a low level of bacteriuria is suspected and is clinically relevant. The system also does not detect anaerobic bacteria, fungi/yeasts, fastidious organisms or those associated with sterile pyuria.

Results Interpretation

A "Presumptive Positive" result indicates that bacteriuria may be present in the sample at a density of ≥5x10 CFU/mL. Samples reported as Presumptive Positive must be cultured for bacteriuria levels, mixed flora evaluation, organism isolation/identification, and antimicrobial susceptibility testing.

A "Presumptive Negative" result may indicate either one of the following:

  • a. No bacteriuria is in the sample,
  • b. Bacteriuria is present at densities below 5x10" CFU/mL, or
  • c. Mixed urogenital flora contaminants (or other organisms not commonly associated with UTI) may be present in the sample, but not detected by the BacterioScan 216Dx.

Samples classified as Presumptive Negative by the 216Dx must be cultured if bacteriuria at densities of <5x10 CFU/mL is suspected and considered clinically relevant. Other laboratory information and clinical symptoms must be considered for final determination of bacteriuria.

Methodology

The BacterioScan 216Dx System uses laser light scattering to measure turbidity (particle density) of a prepared urine-broth sample during a period of incubation. The system is designed to kinetically capture digital measurements of sample turbidity at very low particle densities. Classification software analyzes these optical signal measurements, and interprets increasing turbidity as bacterial growth. Samples with robust growth during the second half of the test cycle, and/or high turbidity, are reported as "Presumptive Positive" for bacteriuria and/or UTI. Low turbidity samples that do not exhibit growth are classified as "Presumptive Negative".

The user logs into the 216Dx interface and is prompted to associate a patient sample ID with a Multicuvette serial number and well location. The user will then pipette the prepared liquid samples into a Multicuvette. Once the Multicuvette is filled, it is loaded into a 216Dx Instrument. The Multicuvette is then incubated for approximately three (3) hours. During the instrument run, the 216Dx appliance will analyze optical measurements to provide a qualitative determination of the presence or absence of viable bacteria in urine specimens at a cut-off of >5x10 CFU/ml. The Classification algorithm qualitatively assesses a result by analyzing periodic measurements taken throughout this incubation period.

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Performance Data

Limit of Detection

A limit of detection (LoD) study was conducted to determine the estimated analytical sensitivity (the lowest organism density detected with an approximate accuracy of ≥95%). For each species of common (10) or rare (7) UTI pathogens, two (2) strains were spiked into fresh, culture-negative human urine. For the initial LoD estimation for each strain, bacteria were spiked into urine, serially diluted to four (4) density levels at approximate clinical cutoff and tested in quadruplicate to determine the approximate LoD. Each strain was then tested in replicates of twenty (20) at the approximated density. LoD was confirmed when density level performance demonstrated >95% or ≥19/20 (Presumptive Positive). Some variation is noted by strain; the final LoD was determined and is reported as the higher of the values. The data demonstrate that the 216Dx has a LoD for most common and rare UTI pathogens that is approximately equivalent to the clinical cut-off of 10° CFU/mL.

The LoD in CFU/mL was confirmed by 100% (20/20) positivity for the following UTI pathogens. The common pathogens with LoD in parenthesis were: E. coli (4.40x103), Proteus mirabilis (8.70x103), Enterobacter cloacae (6.67x103), Staphylococcus aureus (1.11x10³), Klebsiella pneumoniae (1.37 x 10ª), Enterococcus faecalis (2.33x104), and Enterococcus faecium (4.37x104). The rare UTI pathogens were: Acinetobacter baumannii (1.60x10"), Citrobacter freundii/koseri (2.80 x 104), Morganella morganii (4.23x10"), Actinobaculum schaalii (2.80x10*), and Corynebacterium striatum (4.03x10*).

There were UTI pathogens noted to have a LoD that was higher than the clinical cut-off (10° CFU/mL) and are noted in the Limitation of product performance. They were: Pseudomonas aeruginosa (4.87x10~), Staphylococcus saprophyticus (2.20x10~), Streptococcus aqalactiae (1.42x105), Aerococcus spp. (1.77x105), and Corynebacterium urealyticum (2.63x105).

Linearity and Dynamic Range

Three (3) Gram-negative and three (3) Gram-positive common UTI pathogens were spiked into negative human urine and serially diluted to approximate clinical cut-off and tested in quadruplicate to assess the linearity and dynamic range of the 216Dx system. Unspiked, culture-negative urine was also assessed. Results confirm that the dynamic range of detection for each Gram-negative and Gram-positive strain tested spans the range of the clinical cut-off. Most of these results demonstrate that the system's reporting algorithm generates the expected result of Presumptive Positive/Presumptive Negative for multiple UTI pathogens. The following organisms were evaluated and the density level in CFU/mL at which 100% (4/4) samples were positive is indicated in parenthesis: E. coli (2.37×10˚), K. pneumoniae (1.70x10³), E. faecalis (7.33x10~), S. aureus (2.1x10~), P. mirabilis (3.6x10*), and E. faecium (4.03x10 ). E. faecium is noted in the Limitation of product performance. Unspiked urine was 100% negative (4/4).

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Reproducibility

This study was designed to demonstrate the reproducibility of the 216Dx detection of density levels of UTI-associated pathogens present in human urine. Representative strains of a Gram-negative (E. coli) and a Gram-positive (E. faecalis) were spiked into fresh, culturenegative human urine to achieve target densities at three (3) levels: "Low" (<10,000 CFU/mL), "Moderate" (~10,000 CFU/mL) and "High" (>10,000 CFU/mL). Unspiked human urine was used as a negative sample. All samples were blinded and randomized prior to testing and fresh specimens were prepared each day for testing. Each reproducibility panel was tested by three (3) individual sites, with two (2) instruments per site and by two (2) operators in quadruplicate for six (6) non-consecutive days.

A summary of results is presented in Tables 2-7. Performance for High and Moderate densities was ≥95% reproducible across sites and between operators. Specifically, performance ranged from 91.7-100% across six (6) operators, from 94.8-100% across sites, and from 91.7-100% across the six (6) days of testing. Negative samples demonstrated performance of 96.5%.

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Table 2: Reproducibility Performance by Operator

IsolateDensity level(CFU/mL range)# of positive samples (% of total)TotalPositive/Total Tested% Positive(95% CI)
Site 1Site 2Site 3
Operator 1Operator 2Operator 1Operator 2Operator 1Operator 2
E. coliHigh(1.37x105-5.03x105)24 (100)24 (100)24 (100)24 (100)24 (100)22 (91.7)142/14498.61%(95.08%, 99.62%)
Moderate(1.20x104-3.70x104)24 (100)24 (100)24 (100)24 (100)23 (95.8)22 (91.7)141/14497.92%(94.05%, 99.29%)
Low(1.87x103-4.00x103)20 (83.3)19 (79.2)24 (100)24 (100)19 (79.2)19 (79.2)125/14486.81%(80.31%, 91.39%)
All levels(1.87x103-5.03x105)68 (94.4)67 (93.1)72 (100)72 (100)66 (91.7)63 (87.5)408/43294.44%(91.87%, 96.24%)
High + Moderate Only(1.20x104-5.03x105)48 (100)48 (100)48 (100)48 (100)47 (97.9)44 (91.7)283/28898.26%(96.00%, 99.26%)
E. faecalisHigh(2.13x105-3.37x105)24 (100)24 (100)24 (100)24 (100)24 (100)22 (91.7)142/14498.61%(95.08%, 99.62%)
Moderate(2.27x104-4.50x104)24 (100)24 (100)24 (100)24 (100)24 (100)22 (91.7)142/14498.61%(95.08%, 99.62%)
Low(2.37x103-4.93x103)5 (20.8)4 (16.7)10 (41.7)12 (50.0)6 (25.0)7 (29.2)44/14430.56%(23.62%, 38.50%)
All levels(2.37x103-3.37x105)53 (73.6)52 (72.2)58 (80.6)60 (83.3)54 (75.0)51 (70.8)328/43275.93%(71.68%, 79.72%)
High + Moderate Only(2.27x104-3.37x105)48 (100)48 (100)48 (100)48 (100)48 (100)44 (91.7)284/28898.61%(96.48%, 99.46%)

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Table 3: Negative Control Reproducibility Performance by Operator

SampleDensity level (CFU/mL range)# of positive samplesTotal Negative/Total Tested% Negative (95% CI)
Site 1Site 2Site 3
Operator 1Operator 2Operator 1Operator 2Operator 1Operator 2
Unspiked urine<5x101002300139/14496.53% (92.13%, 98.51%)

Table 4: Reproducibility Performance by Site

IsolateDensity level(CFU/mL range)# of positive samples (% of total)TotalPositive/Total Tested% Positive(95% CI)
E. coliHigh(1.37x105-5.03x105)Site 148 (100)Site 248 (100)Site 346 (95.8)142/14498.61%(95.08%, 99.62%)
Moderate(1.20x104-3.70x104)48 (100)48 (100)45 (93.8)141/14497.92%(94.05%, 99.29%)
Low(1.87x103-4.00x103)39 (81.3)48 (100)38 (79.2)125/14486.81%(80.31%, 91.39%)
All levels(1.87x103-5.03x105)135 (93.8)144 (100)129 (89.6)408/43294.44%(91.87%, 96.24%)
High + Moderate Only(1.20x104-5.03x105)96 (100)96 (100)91 (94.8)283/28898.26%(96.00%, 99.26%)
E. faecalisHigh(2.13x105-3.37x105)48 (100)48 (100)46 (95.8)142/14498.61%(95.08%, 99.62%)
Moderate(2.27x104-4.50x104)48 (100)48 (100)46 (95.8)142/14498.61%(95.08%, 99.62%)
Low(2.37x103-4.93x103)9 (18.8)22 (45.8)13 (27.1)44/14430.56%(23.62%, 38.50%)
All levels(2.37x103-3.37x105)105 (72.9)118 (81.9)105 (72.9)328/43275.93%(71.68%, 79.72%)
High + Moderate Only(2.27x104-3.37x105)96 (100)96 (100)92 (95.8)284/28898.61%(96.48%, 99.46%)

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Table 5: Negative Control Reproducibility Performance by Site

SampleDensity level(CFU/mL range)# of positive samplesTotal Negative/Total Tested% Negative(95% CI)
Unspikedurine<5x101050139/14496.53%(92.13%, 98.51%)

Table 6: Reproducibility Performance by Day

IsolateDensity level(CFU/mL range)# of positive samples (% of total)TotalPositive/Total Tested% Positive(95% CI)
Day 1Day 2Day 3Day 4Day 5Day 6
E. coliHigh(1.37x105-5.03x105)22 (91.7)24 (100)24 (100)24 (100)24 (100)24 (100)142/14498.61%(95.08%, 99.62%)
Moderate(1.20x104-3.70x104)22 (91.7)24 (100)24 (100)24 (100)23 (95.8)24 (100)141/14497.92%(94.05%, 99.29%)
Low(1.87x103-4.00x103)21 (87.5)23 (95.8)23 (95.8)21 (87.5)18 (75.0)19 (79.2)125/14486.81%(80.31%, 91.39%)
All levels(1.87x103-5.03x105)65 (90.3)71 (98.6)71 (98.6)69 (95.8)65 (90.3)67 (93.1)408/43294.44%(91.87%, 96.24%)
High + Moderate Only(1.20x104-5.03x105)44 (91.7)48 (100)48 (100)48 (100)47 (97.9)48 (100)283/28898.26%(96.00%, 99.26%)
E. faecalisHigh(2.13x105-3.37x105)22 (91.7)24 (100)24 (100)24 (100)24 (100)24 (100)142/14498.61%(95.08%, 99.62%)
Moderate(2.27x104-4.50x104)22 (91.7)24 (100)24 (100)24 (100)24 (100)24 (100)142/14498.61%(95.08%, 99.62%)
Low(2.37x103-4.93x103)4 (16.7)5 (20.8)12 (50.0)7 (29.2)13 (54.2)3 (12.5)44/14430.56%(23.62%, 38.50%)
All levels(2.37x103-3.37x105)48 (66.7)53 (73.6)60 (91.7)55 (76.4)61 (84.7)51 (70.8)328/43275.93%(71.68%, 79.72%)
High + Moderate Only(2.27x104-3.37x105)44 (91.7)48 (100)48 (100)48 (100)48 (100)48 (100)284/28898.61%(96.48%, 99.46%)

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Table 7: Negative Control Reproducibility Performance by Day

SampleDensity level(CFU/mL range)# of positive samplesTotal Negative/Total Tested% Negative(95% CI)
Unspikedurine<5x10¹020102139/14496.53%(92.13%, 98.51%)

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Analytical Inclusivity

To demonstrate analytical inclusivity, multiple strains of each common and rare UTI pathogen were tested on the 216Dx. All strains were spiked into fresh, culture-negative human urine, serially diluted to a bacteriuria/density of approximately 2-3X LoD for each individual organism to be tested. All samples were evaluated in quadruplicate. There were ten (10) common and seven (7) rare uropathogens comprising of eighty five (85) and eighteen (18) strains respectively tested in the inclusivity study. The common uropathogens tested were Escherichia coli (10), Klebsiella pneumoniae (9), Enterobacter spp. (8), Pseudomonas aeruginosa (9), Proteus mirabilis (9), Enterococcus faecalis (8), Enterococcus faecium (5), Staphylococcus aureus (9), Staphylococcus saprophyticus (9), and Streptococcus agalactiae(9); the positivity rate was 98.8% (336/340). The rare uropathogens tested were Acinetobacter baumannii (3), Actinobaculum schaalii(1), Aerococcus spp. (3), Citrobacter spp. (5), Corynebacterium striatum (1), Corynebacterium urealyticum (1), and Morganella morqanii (4); the positivity rate was 100% (72/72). The unspiked urine was 100% negative (8/8).

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Interfering Substances/Microbial Interference

This study was conducted to evaluate 216Dx performance in the presence of (a) potentially interfering endogenous or exogenous substances that may be found in urine, or (b) various organisms present in urine that are not expected to grow under the standard conditions used for urine culture and/or in the BacterioScan system. Representative strains of four (4) Gram-negative and three (3) Gram-positive UTI pathogens at 2-3 X LoD density level were spiked into fresh, culture-negative human urine that had first been spiked with an interfering substance/microorganism. A corresponding unspiked urine control was included for each interfering substance/organism. There were a total of nineteen (19) interfering substances (albumin, glucose, phenazopyridine, seminal fluid, acidic urine, alkaline urine, talcum powder, blood, bilirubin, acetaminophen, mucin, human Chorionic Gonadotrophin (hCG), testosterone, cortisol, progesterone, leukocytes, fluconazole, and flucytosine) and three (3) interfering organisms (H. influenzae, H. parainfluenzae, and N. gonorrhoeae) evaluated in the study. To confirm that the 216Dx could detect each organism at the densities tested, corresponding urine samples lacking each interfering substance/microorganism were processed in parallel and evaluated in the 216Dx concurrently. All samples were evaluated in replicates of four (4).

The results indicate that the majority of potential substances that may be found in human urine do not interfere with the 216Dx's performance. The following substances were noted to interfere with performance when present in high concentrations: Phenazopyridine (>200 μg/mL), blood (>0.0156%), bilirubin (>20 µg/mL), mucin (>0.039%, v/v), and leukocytes (>10 cells/mL); talcum powder (0.4% w/v) and H. parainfluenzae (1.1x10 CFU/mL) demonstrated interference (i.e. false positivity), and acidic urine (pH 6.0) may interfere with the positivity of Enterobacter cloacae at density levels of ≤5x10* CFU/mL. Further, the study showed that there were instances in which S. aureus did not give positive results at density level of 10 CFU/mL. These interfering substances are noted in the limitation section of the labeling defining potential interference. Potential sources of interference have been specified in the Limitations section (see BacterioScan 216Dx Package Insert).

Method Comparison

A comparison study was conducted at three (3) geographically diverse sites, each testing approximately 1,000 urine samples received in the laboratory for routine urine culture. Samples were tested in accordance to BacterioScan instructions for use. Each urine was diluted to a 1:8 into TSB (360μL of urine with 2.5mL TSB). Controls were run each day of testing on each instrument used.

Reference cultures were performed simultaneously with 216Dx testing. Reference testing was performed using 1- and 10μL loops. Using each loop, colony count plates were performed in triplicate, and a median result was generated for each loop size. Median colony count was determined to be the reference result and were compared to the 216Dx result. Any colony counts at or above 5x10 ° CFU/mL are considered a positive result for primary analysis and a secondary analysis specific to UTI pathogens (UTI-Associated) was also performed. Organisms isolated from reference colony counts of ≥5x10* CFU/mL were identified by MALDI.

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The detection algorithm used by the BacterioScan 216Dx was designed to classify urine specimens containing UTI associated bacteria at a density of >5x10 ° CFU/mL. Samples measured and containing bacteriuria/total density of >5x10 € CFU/mL organisms is reported by the BacterioScan 216Dx to be "Presumptive Positive." Data were analyzed based on reference colony counts of ≥5x10 or ≥1x10 °CFU/mL and identification of isolated organisms by MALDI. In the secondary analysis, the common UTI pathogens (UTI Associated) encountered were: Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Proteus mirabilis, Enterobacter cloacae, Pseudomonas aeruginosa, Enterococcus faecalis, Enterococcus faecium, Aerococcus urinae, Streptocccus agalactiae, and Staphylococcus aureus; the rare uropathogens encountered were Enterobacter aerogenes, Citrobacter freundii, Citrobacter koseri, Acinetobacter baumannii, Morqanella morqanii, Aerococcus sanquinicola, Corynebacterium striatum, and Staphylococcus saprophyticus.

The results of this comparative study demonstrate the performance of the 216Dx in detecting bacteria in urine with an emphasis on UTI-associated pathogens at densities ≥5x10* CFU/mL. Performance was also evaluated at bacterial densities >1x10* CFU/mL as a subpopulation. Of the 3,153 urine samples enrolled, there were a total of 3,052 evaluable specimens for primary analysis of bacteriuria. For the secondary analysis, the evaluable specimens were 3,010 for ≥5x10* CFU/mL but 3,020 for ≥1x10 ° CFU/mL because the identity of some organisms was not obtained in the reference culture at the defined cut-off of ≥5x10* CFU/mL. Performance at these levels demonstrates a substantial equivalence to the reference method in detecting bacteria in urine with an emphasis on UTI associated organisms at a clinically significant density of ≥5x10 € CFU/mL. Further analyses of the study data demonstrate that the BacterioScan 216Dx performance is substantially equivalent regarding patient gender. Analysis by study site can be found in Tables 10-12, patient gender (Tables 13, 14), and the urine specimens collected with (preserved) or without (unpreserved) preservatives prior to analysis (Tables 15-18).

All BacterioScan 216Dx results are presumptive.

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Overall Performance for Bacterial Density of ≥5x104 CFU/mL
Primary Analysis:BacteriuriaSecondary Analysis:UTI Associated*
ReferenceReference
PositiveNegativeTotalPositiveNegativeTotal
BacterioScan216DxPositive71457612905926721264
Negative87167517621417321746
Total8012251305260624043010
Sensitivity89.1% (714/801)95% CI: 86.8%; 91.1%97.7% (592/606)95% CI: 96.2%; 98.6%
Specificity74.4% (1675/2251)95% CI: 72.6%; 76.2%72.0 (1732/2404)95% CI: 70.2%; 73.8%
PPV55.3% (714/1290)95% CI: 52.6%; 58.0%46.8% (592/1264)95% CI: 44.1%; 49.6%
NPV95.1% (1675/1762)95% CI: 93.9%; 96.0%99.2% (1732/1746)95% CI: 98.7%; 99.5%

Limited to bacterial pathogens encountered in the clinical studies

Table 9

Performance for Subpopulation of ≥1x105 CFU/mL
Primary Analysis:BacteriuriaSecondary Analysis:UTI Associated*
PositiveNegativeTotalPositiveNegativeTotal
BacterioScan216Dx58170912905017671268
Negative4017221762717451752
Total6212431305250825123020
Sensitivity93.6% (581/621)95% CI: 91.3%; 95.2%98.6% (501/508)95% CI: 97.2%; 99.3%
Specificity70.8% (1722/2431)95% CI: 69.0%; 72.6%69.5% (1745/2512)95% CI: 67.6%; 71.2%
PPV45.0% (581/1290)95% CI: 42.3%; 47.8%39.5% (501/1268)95% CI: 36.9%; 42.2%
NPV97.7% (1722/1762)95% CI: 96.9%; 98.3%99.6% (1745/1752)95% CI: 99.2%; 99.8%

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Site 1 Performance for Bacterial Density of ≥5x104 CFU/mL
Primary Analysis:BacteriuriaSecondary Analysis:UTI Associated*
ReferenceReference
PositiveNegativeTotalPositiveNegativeTotal
BacterioScan216DxPositive258212470226238464
Negative145245382531533
Total2727361008228769997
Sensitivity94.9% (258/272)99.1% (226/228)
95% CI: 91.5%; 96.9%95% CI: 96.9%; 99.8%
Specificity71.2% (524/736)69.1% (531/769)
95% CI: 67.8%; 74.4%95% CI: 65.7%; 72.2%
PPV54.9% (258/470)48.7% (226/464)
95% CI: 50.4%; 59.3%95% CI: 44.2%; 53.2%
NPV97.4% (524/538)99.6% (531/533)
95% CI: 95.7%; 98.4%95% CI: 98.6%; 99.9%
  • Limited to bacterial pathogens encountered in the clinical studies

Table 11

Site 2 Performance for Bacterial Density of ≥5x10⁴ CFU/mL
Primary Analysis:BacteriuriaSecondary Analysis:UTI Associated *
ReferenceReference
PositiveNegativeTotalPositiveNegativeTotal
BacterioScan216DxPositive180162342139191330
Negative366556914681685
Total21681710331438721015
Sensitivity83.3% (180/216)97.2% (139/143)
95% CI: 77.8%; 87.7%95% CI: 93.0%; 98.9%
Specificity80.2% (655/817)78.1% (681/872)
95% CI: 77.3%; 82.8%95% CI: 75.2%; 80.7%
PPV52.6% (180/342)42.1% (139/330)
95% CI: 47.3%; 57.9%95% CI: 36.9%; 47.5%
NPV94.8% (655/691)99.4% (681/685)
95% CI: 92.9%; 96.2%95% CI: 98.5%; 99.8%

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Site 3 Performance for Bacterial Density of ≥5x104 CFU/mL
Primary Analysis:BacteriuriaSecondary Analysis:UTI Associated*
ReferenceReference
PositiveNegativeTotalPositiveNegativeTotal
BacterioScan216DxPositive276202478227243470
Negative374965338520528
Total3136981011235763998
Sensitivity88.2% (276/313)95% CI: 84.1%; 91.3%96.6% (227/235)95% CI: 93.4%; 98.3%
Specificity71.1% (496/698)95% CI: 67.6%; 74.3%68.2% (520/763)95% CI: 64.8%; 71.4%
PPV57.7% (276/478)95% CI: 53.3%; 62.1%48.3% (227/470)95% CI: 43.8%; 52.8%
NPV93.1% (496/533)95% CI: 90.6%; 94.9%98.5% (520/528)95% CI: 97.0%; 99.2%
  • Limited to bacterial pathogens encountered in the clinical studies

Table 13

Performance for Bacterial Density of ≥5x104 CFU/mL (Male)
Primary Analysis:BacteriuriaSecondary Analysis:UTI Associated *
ReferenceReference
PositiveNegativeTotalPositiveNegativeTotal
BacterioScan216DxPositive127154281101172273
Negative65775833580583
Total133731864104752856
Sensitivity95.6% (127/133)95% CI: 90.5%; 97.9%97.1% (101/104)95% CI: 91.9%; 99.0%
Specificity78.9% (577/731)95% CI: 75.8%; 81.7%77.1% (580/752)95% CI: 74.0%; 80.0%
PPV45.2% (127/281)95% CI: 39.5%; 51.0%37.0% (101/273)95% CI: 31.5%; 42.9%
NPV99.0% (577/583)95% CI: 97.8%; 99.5%99.5% (580/583)95% CI: 98.5%; 99.8%

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Performance for Bacterial Density of ≥5x10⁴ CFU/mL (Female)
Primary Analysis:BacteriuriaSecondary Analysis:UTI Associated *
ReferenceReference
PositiveNegativeTotalPositiveNegativeTotal
BacterioScan216DxPositive5874221009491500991
Negative81109411791111521163
Total6681520218850216522154
Sensitivity87.9% (587/668)95% CI: 85.2%; 90.1%97.8% (491/502)95% CI: 96.1%; 98.8%
Specificity72.2% (1094/1520)95% CI: 69.9%; 74.4%69.7% (1152/1652)95% CI: 67.5%; 71.9%
PPV58.2% (587/1009)95% CI: 55.1%; 61.2%49.5% (491/991)95% CI: 46.4%; 52.7%
NPV93.1% (1094/1179)95% CI: 91.5%; 94.4%99.1% (1152/1163)95% CI: 98.3%; 99.5%
  • Limited to bacterial pathogens encountered in the clinical studies

Table 15

Overall Performance for Bacterial Density of ≥5x104 CFU/mL (Unpreserved Samples)
Primary Analysis:BacteriuriaSecondary Analysis:UTI Associated*
PositiveNegativeTotalPositiveNegativeTotal
BacterioScan216DxPositive13112025197143240
Negative294464754465469
Total160566726101608709
Sensitivity81.9% (131/160)95% CI: 75.2%; 87.1%96.0% (97/101)95% CI: 90.3%; 98.4%
Specificity78.8% (446/566)95% CI: 75.2%; 82.0%76.5% (465/608)95% CI: 72.9%; 79.7%
PPV52.2% (131/251)95% CI: 46.0%; 58.3%40.4% (97/240)95% CI: 34.4%; 46.7%
NPV93.9% (446/475)95% CI: 91.4%; 95.7%99.15% (465/469)95% CI: 97.8%; 99.7%

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Performance for Subpopulation of ≥1x105 CFU/mL (Unpreserved Samples)
Primary Analysis:BacteriuriaSecondary Analysis:UTI Associated *
ReferenceReference
PositiveNegativeTotalPositiveNegativeTotal
BacterioScan216DxPositive10614525178162240
Negative144614752469471
Total12060672680631711
Sensitivity88.3% (106/120)97.5% (78/80)
95% CI: 81.4%; 92.9%95% CI: 91.3%; 99.3%
Specificity76.1% (461/606)74.3% (469/631)
95% CI: 72.5%; 79.3%95% CI: 70.8%; 77.6%
PPV42.2% (106/251)32.5% (78/240)
95% CI: 36.3%; 48.4%95% CI: 26.9%; 38.7%
NPV97.1% (461/475)99.6% (469/471)
95% CI: 95.1%; 98.2%95% CI: 98.5%; 99.9%
  • Limited to bacterial pathogens encountered in the clinical studies

Table 17

Overall Performance for Bacterial Density of ≥5x104 CFU/mL (Preserved Samples)
Primary Analysis:BacteriuriaSecondary Analysis:UTI Associated*
ReferenceReference
PositiveNegativeTotalPositiveNegativeTotal
BacterioScan216DxPositive58345610394955291024
Negative58122912871012671277
Total6411685232650517962301
Sensitivity91.0% (583/641)95% CI: 88.5%; 92.9%98.0% (495/505)95% CI: 96.4%; 98.9%
Specificity72.9% (1229/1685)95% CI: 70.8%; 75.0%70.5% (1267/1796)95% CI: 68.4%; 72.6%
PPV56.1% (583/1039)95% CI: 53.1%; 59.1%48.3% (495/1024)95% CI: 45.3%; 51.4%
NPV95.5% (1229/1287)95% CI: 94.2%; 96.5%99.2% (1267/1277)95% CI: 98.6%; 99.6%

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Table18
-------------
Performance for Subpopulation of ≥1x10⁵ CFU/mL (Preserved Samples)
Primary Analysis:Secondary Analysis:
BacteriuriaUTI Associated
ReferenceReference
PositiveNegativeTotalPositiveNegativeTotal
BacterioScanPositive47556410394236051028
216DxNegative2612611287512761281
Total5011825232642818812309
Sensitivity94.8% (475/501)98.8% (423/428)
95% CI: 92.5%; 96.4%95% CI: 97.3%; 99.5%
Specificity69.1% (1261/1825)67.8% (1276/1881)
95% CI: 66.9%; 71.2%95% CI: 65.7%; 69.9%
PPV45.7% (475/1039)41.1% (423/1028)
95% CI: 42.7%; 48.8%95% CI: 38.2%; 44.2%
NPV98.0% (1261/1287)99.6% (1276/1281)
95% CI: 97.1%; 98.6%95% CI: 99.1%; 99.8%

Limited to bacterial pathogens encountered in the clinical studies

The BacterioScan 216Dx detects bacteria in urine, with improved performance specific to organisms associated with UTI, and reduces turn-around-time from 24 hours to approximately three (3) hours, delivering a faster time to result for the majority of UTI specimens.

Statement of Safety and Effectiveness

The data presented demonstrates the safety and efficacy of the BacterioScan 216Dx System as compared to the reference method when the product Instructions for Use are followed.

§ 866.2560 Microbial growth monitor.

(a)
Identification. A microbial growth monitor is a device intended for medical purposes that measures the concentration of bacteria suspended in a liquid medium by measuring changes in light scattering properties, optical density, electrical impedance, or by making direct bacterial counts. The device aids in the diagnosis of disease caused by pathogenic microorganisms.(b)
Classification. Class I. With the exception of automated blood culturing system devices that are used in testing for bacteria, fungi, and other microorganisms in blood and other normally sterile body fluids, this device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter.