REMEL SPECTRA MRSA

K092407 · Remel, Inc. · JSO · Oct 8, 2010 · Microbiology

Device Facts

• Record ID: K092407
• Device Name: REMEL SPECTRA MRSA
• Applicant: Remel, Inc.
• Product Code: JSO · Microbiology
• Decision Date: Oct 8, 2010
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 866.1700
• Device Class: Class 2

Intended Use

Remel Spectra™ MRSA is a selective and differential chromogenic medium recommended for use in the qualitative detection of nasal colonization of methicillin-resistant Staphylococcus aureus (MRSA) to aid in the prevention and control of MRSA in healthcare settings. The test is performed with anterior nares swab specimens from patients and healthcare workers to screen for MRSA colonization. Spectra™ MRSA is not intended to diagnose MRSA infection or to guide or monitor treatment for infections. Spectra™ MRSA is also intended for use in the qualitative detection of MRSA from positive blood cultures demonstrating Gram-positive cocci on Gram stain. Spectra™ MRSA is indicated for use in conjunction with other laboratory tests and clinical data available to the clinician as an aid in the detection of MRSA from patient positive blood cultures. Spectra™ MRSA is not intended to monitor treatment for MRSA infections, or provide results of susceptibility to methicillin. All positive blood bottles should be sub-cultured for further microbiological/susceptibility testing.

Device Story

Selective/differential chromogenic culture medium; detects MRSA via phosphatase activity producing denim-blue colonies. Input: anterior nares swabs or positive blood culture samples (Gram-positive cocci). Operation: manual inoculation/incubation (24 hours); antibacterial compounds inhibit competitor organisms; pathogenicity markers enhance phosphatase expression. Output: visual identification of denim-blue colonies. Used in clinical microbiology laboratories; interpreted by laboratory technicians. Results aid clinicians in MRSA detection from blood cultures; requires sub-culturing for definitive susceptibility testing. Benefits: rapid screening/detection to support infection control and clinical decision-making.

Clinical Evidence

Clinical performance evaluated at four US sites using 547 positive blood cultures (158 MRSA, 389 non-MRSA). Compared to traditional subculture on Blood Agar (48h) and PBP2' testing. Results: 96.2% sensitivity (95% CI: 91.9–98.6%) and 100% specificity (95% CI: 99.2–100%) vs. traditional culture. Compared to PBP2', sensitivity was 97.4% (95% CI: 93.4–99.3%) and specificity was 99.0% (95% CI: 97.4–99.6%).

Technological Characteristics

Selective and differential chromogenic prepared culture medium. Contains chromogenic substrate for phosphatase activity, antibacterial inhibitors, and pathogenicity marker enhancers. Form factor: opaque agar plate. Manual reading. No electronic components or software.

Indications for Use

Indicated for qualitative detection of MRSA from anterior nares swabs (nasal colonization screening) and positive blood cultures (demonstrating Gram-positive cocci) in patients and healthcare workers. Not for diagnosing MRSA infection, monitoring treatment, or providing methicillin susceptibility results.

Regulatory Classification

Identification

A culture medium for antimicrobial susceptibility tests is a device intended for medical purposes that consists of any medium capable of supporting the growth of many of the bacterial pathogens that are subject to antimicrobial susceptibility tests. The medium should be free of components known to be antagonistic to the common agents for which susceptibility tests are performed in the treatment of disease.

Predicate Devices

• Remel Spectra™ MRSA (Nasal) (k073027)

Submission Summary (Full Text)

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# 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY ONLY TEMPLATE

A. 510(k) Number:
k092407

B. Purpose for Submission:
To obtain a substantial equivalence determination for Remel Spectra™ MRSA for use in the qualitative detection of MRSA from positive blood cultures demonstrating Gram positive cocci on Gram stain

C. Measurand:
Methicillin Resistant *Staphylococcus aureus* (MRSA)

D. Type of Test:
A selective and differential chromogenic media for detection of MRSA

E. Applicant:
Thermo Fisher Scientific

F. Proprietary and Established Names:
Remel Spectra™ MRSA

G. Regulatory Information:
1. Regulation section:
21CFR 866.1700 Culture medium for antimicrobial susceptibility tests
2. Classification:
II
3. Product code:
JSO

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4. Panel:
83-Microbiology

H. Intended Use:

1. Intended use(s):

Remel Spectra™ MRSA is a selective and differential chromogenic medium recommended for use in the qualitative detection of nasal colonization of methicillin-resistant Staphylococcus aureus (MRSA) to aid in the prevention and control of MRSA in healthcare settings. The test is performed with anterior nares swab specimens from patients and healthcare workers to screen for MRSA colonization. Spectra™ MRSA is not intended to diagnose MRSA infection or to guide or monitor treatment for infections.

Spectra™ MRSA is also intended for use in the qualitative detection of MRSA from positive blood cultures demonstrating Gram-positive cocci on Gram stain. Spectra™ MRSA is indicated for use in conjunction with other laboratory tests and clinical data available to the clinician as an aid in the detection of MRSA from patient positive blood cultures. Spectra™ MRSA is not intended to monitor treatment for MRSA infections, or provide results of susceptibility to methicillin. All positive blood bottles should be sub-cultured for further microbiological/susceptibility testing.

2. Indication(s) for use:

Remel Spectra™ MRSA is a selective and differential chromogenic medium recommended for use in the qualitative detection of nasal colonization of methicillin-resistant Staphylococcus aureus (MRSA) to aid in the prevention and control of MRSA in healthcare settings. The test is performed with anterior nares swab specimens from patients and healthcare workers to screen for MRSA colonization. Spectra™ MRSA is not intended to diagnose MRSA infection or to guide or monitor treatment for infections.

Spectra™ MRSA is also intended for use in the qualitative detection of MRSA from positive blood cultures demonstrating Gram-positive cocci on Gram stain. Spectra™ MRSA is indicated for use in conjunction with other laboratory tests and clinical data available to the clinician as an aid in the detection of MRSA from patient positive blood cultures. Spectra™ MRSA is not intended to monitor treatment for MRSA infections, or provide results of susceptibility to methicillin. All positive blood bottles should be sub-cultured for further microbiological/susceptibility testing.

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3. Special conditions for use statement(s):

For prescription use only.

4. Special instrument requirements:

Not applicable

I. Device Description:

Remel Spectra™ MRSA is an opaque medium, which uses a novel chromogen that yields a denim-blue color as a result of phosphatase activity. This enzyme is present in Staphylococcus aureus, including MRSA. To allow the medium to differentiate MRSA accurately, it contains a combination of antibacterial compounds designed to inhibit the growth of a wide variety of competitor organisms. Also included are compounds that encourage the production of MRSA pathogenicity marker, ensuring expression of the phosphatase enzyme and so providing enhanced sensitivity and specificity.

J. Substantial Equivalence Information:

1. Predicate device name(s):

Remel Spectra™ MRSA (Nasal)

2. Predicate K number(s):

k073027

3. Comparison with predicate:

| Similarities | | |
| --- | --- | --- |
| Item | Device | Predicate |
| Intended Use | For MRSA detection | For MRSA detection |
| Reporting | MRSA | MRSA |
| Reading | Manual | Manual |
| Test Methodology | selective and differential chromogenic prepared culture medium | selective and differential chromogenic prepared culture medium |
| Incubation | 24 hours | 24 hours |
| Differences | | |
| --- | --- | --- |
| Item | Device | Predicate |
| Inoculum | Positive blood culture | Anterior nares swabs |
| | | |

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K. Standard/Guidance Document Referenced (if applicable):

Not applicable.

L. Test Principle:

Remel Spectra™ MRSA is an opaque medium, which uses a novel chromogen that yields a denim-blue color as a result of phosphatase activity. This enzyme is present in all Staphylococcus aureus, including MRSA. To allow the medium to differentiate MRSA accurately, it contains a combination of antibacterial compounds designed to inhibit the growth of a wide variety of competitor organisms. Also included are compounds that encourage the production of MRSA pathogenicity marker, ensuring expression of the phosphatase enzyme and so providing enhanced sensitivity and specificity.

M. Performance Characteristics (if/when applicable):

1. Analytical performance:

a. Precision/Reproducibility:

Reproducibility was demonstrated at six sites using a panel of 20 S. aureus strains including thirteen MRSA, six MSSA, and one borderline oxacillin-resistant S. aureus (BORSA) isolates. Each isolate was tested once on each of three days at each site resulting in 360 data points. All were in agreement with expected values at 24 hours. The BORSA strain included in this evaluation at four sites is considered variable and produced a positive test result for 7/12 data points at 24 hours.

b. Linearity/assay reportable range:

Not applicable

c. Traceability, Stability, Expected values (controls, calibrators, or methods):

The recommended quality control (QC) organisms, S. aureus ATCC 43300 as positive control, and S. aureus ATCC 25923 as negative control were used. The clinical trial was conducted at four independent trial sites from July 31, 2007 through February 16, 2009. Weekly QC testing was conducted each week of testing clinical specimens utilizing CLSI interpretive criteria where applicable. All QC results obtained were acceptable.

d. Detection limit:

Not applicable.

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e. Analytical specificity:

Cross-reactivity

Although cross reactivity studies were conducted as part of the anterior nares culture submission (k073027), additional studies were conducted to test for cross-reactivity with organisms that may be isolated from blood cultures because of the indication for use with blood culture bottles. In total, two hundred ninety-seven isolates were tested as part of this submission and 280 were tested as part of the earlier k073027 submission) microorganisms representing gram-negative rods, yeast, streptococci, enterococci, staphylococci and related organisms were evaluated with Spectra™ MRSA at 10⁵–10⁶ colony-forming units per ml concentration. No cross-reactivity (denim blue colonies) was observed following 24 hours incubation.

Supplemental cross reactivity studies were added as part of this submission. This included oxacillin MIC values against 97 coagulase negative staphylococci (27 isolates were resistant to oxacillin). No cross reactivity (denim blue colonies) was seen with any of these organisms following 24 hours incubation.

Interfering Substances

Interfering substances studies were conducted as part of the anterior nares culture submission (k073027). Nine commonly used medicinal substances, human blood, mucous, and six types of transport media were evaluated for potential interference of the chromogenic reaction on the Spectra™ MRSA medium. No interference was observed except for human blood which grew pinpoint denim blue colonies.

f. Analytical sensitivity

Recovery study

A study was conducted to evaluate the recovery of methicillin-resistant Staphylococcus aureus (MRSA) on Remel Spectra™ MRSA subcultured from positive blood cultures that also contain organisms that could potentially be co-present in the positive blood culture. The following organisms were evaluated: methicillin-susceptible Staphylococcus aureus (MSSA) and methicillin-resistant Staphylococcus epidermidis (MRCoNS).

Blood culture bottles were spiked with blood and various concentrations of MRSA, MSSA and MRCoNS. Post-spiking, each bottle was incubated at 35–37°C for 6 hours.

This study was designed based on the limit of detection (LoD) of 10⁴ CFU/mL

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determined from pilot spiking studies in various blood culture bottle types. The recovery of MRSA (at $10^{4}$ CFU/mL) was challenged with MSSA and MRCoNS at LoD and higher concentrations of $10^{6}$ and $10^{8}$ CFU/mL, in order to determine the impact of interfering organism on the detection of the target.

As shown in Table 1, the results from this study indicated that Spectra™ MRSA is capable of detection of MRSA ATCC 43300 from various blood culture bottles whether MRSA was alone or mixed with a heavy inoculum of MSSA and/or MRCoNS after 6 hours of incubation. Although similar results were seen with MRSA ATCC® 43300, a heteroresistant isolate, recovery of this strain was generally low and especially on the VersaTrek REDOX 2 (anaerobic) blood culture bottle.

Overall results from this recovery study demonstrated the ability of Spectra MRSA to support growth of MRSA within the confines of a six hour incubation limit when the organism was either alone or mixed with competing Staphylococci (MSSA or MRCoNS).

Table 1: Average of MRSA recovery on Spectra MRSA plate upon subculture of each blood culture bottle incubated for 6 hours

| Blood Culture Medium | MRSA Strain and Agar Plate | | | |
| --- | --- | --- | --- | --- |
| | ATCC 43300 | | ATCC 33591 | |
| | SPECTRA | Blood Agar | SPECTRA | Blood Agar |
| Bactec Plus Aerobic F | 53.7 | 75 | 64.6 | 58 |
| Bactec Standard/10 Aerobic/F | 28 | 35 | 39.3 | 50 |
| Bactec Ped Plus/F | 18.3 | 20 | 79.7 | 80 |
| Bactec Lytic/10 Anaerobic/F | 19.6 | 45 | 12.3 | 19 |
| bioMerieux BacT/ALERT FA FAN Aerobic | 38 | 60 | 107.7 | 100 |
| bioMerieux BacT/ALERT FN FAN Anaerobic | 25 | 30 | 41.7 | 25 |
| VersaTrek REDOX 1 Aerobic | 14.7 | 18 | 16.7 | 7 |
| VersaTrek REDOX 2 Anaerobic | 3.7 | 10 | 36 | 47 |

NOTE: ATCC® 43300 inoculum control = 3 colony forming units
ATCC® 33591 inoculum control = 12 colony forming units

g. Assay cut-off:

Not applicable

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# 2. Comparison studies:

# a. Method comparison with predicate device:

The performance of Spectra™ MRSA was evaluated at four geographically diverse regions of the United States. Results from the Spectra™ MRSA at 24 hours incubation were compared to results obtained from traditional subculture on Tryptic Soy Agar with $5\%$ Sheep Blood (Blood Agar) after 48 hours incubation. Suspect isolates of S. aureus were identified using a latex agglutination test or a biochemical identification system. Susceptibility testing was performed using an antibiotic gradient method for oxacillin and the Oxoid PBP2' test was used for the detection of the penicillin-binding protein 2a.

A total of six hundred twenty eight (628) positive blood cultures exhibiting gram-positive cocci on initial microscopic examination were tested. Upon evaluation of the data submitted, a total of 81 Spectra™ MRSA results obtained from subculture of the following blood culture bottles were excluded from the primary analysis for the reasons stated:

1. BACTEC Lytic/10 Anaerobic/F and Standard/10 Aerobic/F because of the inability to separate the data for each bottle type
2. BACTEC Ped Plus because none were positive for MRSA

Because of these exclusions, the total blood cultures considered for evaluation of the performance of Spectra™ MRSA at 24 hours was reduced from 628 to 547 (158 MRSA and 389 non-MRSA).

The overall recovery of MRSA on Spectra™ MRSA at 24 hours was $96.2\%$ (152/158) compared to recovery of $100\%$ (158/158) on Blood Agar at 48 hours. The positive and negative predictive values for Spectra™ MRSA compared to the Oxoid PBP2' test were $97.4\%$ and $99.0\%$ respectively as shown in Table 2. Overall Performance vs. Traditional Culture and/or Oxacillin MIC is shown in Table 3 and Overall Performance vs. PBP2 is shown in Table 4. Detailed performance is provided in Tables 5 and 6.

Table 2: Overall Performance Summary

| | MRSA | Non-MRSA |
| --- | --- | --- |
| Spectra™ MRSA vs. traditional culture* | 96.2% (152/158) (95% CI = 91.9–98.6%) | 100% (389/389) (95% CI = 99.2–100%) |
| Spectra™ MRSA vs. PBP2' | 97.4% (148/152) (95% CI = 93.4–99.3%) | 99.0% (391/395) (95% CI = 97.4–99.6%) |
| Spectra™ MRSA vs. Oxacillin MIC* | 96.2% (152/158) (95% CI = 91.9–98.6%) | 100% (389/389) (95% CI = 99.2–100%) |

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*Six strains included as MRSA with oxacillin MICs of $4 - 6\mu \mathrm{g / ml}$ that tested PBP 2a negative. Per the CLSI M100-S19 document, these types of strains should be reported as oxacillin resistant.

Note : CI = Confidence Interval

Table 3: Overall Performance vs. Traditional Culture and/or Oxacillin MIC

| n=547 | Traditional Culture / Oxacillin MIC | | |
| --- | --- | --- | --- |
| | | + | - |
| Spectra™ | + | 152 | 0 |
| MRSA | - | 6 | 389 |
| TOTAL | | 158 | 389 |

MRSA Agreement 96.2% (152/158) (95% CI = 91.9–98.6%)

Non-MRSA Agreement 100% (389/389) (95% CI = 99.2-100%)

Overall Agreement 98.9% (541/547) (95% CI = 97.6-99.6%)

Positive Predictive Value 100% (152/152) (95% CI = 98.1-100%)

Negative Predictive Value 98.5% (389/395) (95% CI = 96.7-99.4%)

Table 4: Overall Performance vs. PBP2

| n=547 | PBP2 | | |
| --- | --- | --- | --- |
| | | + | - |
| Spectra™ | + | 148 | 4 |
| MRSA | - | 4 | 391 |
| TOTAL | | 152 | 395 |

MRSA Agreement 97.4% (148/152) (95% CI = 93.4-99.3%)

Non-MRSA Agreement 99.0% (391/395) (95% CI = 97.4-99.6%)

Overall Agreement 98.5% (539/547) (95% CI = 97.1-99.3%)

Positive Predictive Value 97.4% (148/152) (95% CI = 93.4-99.3%)

Negative Predictive Value 99.0% (391/395) (95% CI = 97.4-99.6%)

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Table 5: Performance of Spectra™ MRSA vs. PBP2'by blood culture bottle type

| Blood Culture Information | Blood Culture Bottle Type | #Spectra™ Pos MRSA/ #Total MRSA | MRSA Agreement (95% CI) | Non-MRSA Agreement (95% CI) | Positive Predictive Value (95% CI) | Negative Predictive Value (95% CI) |
| --- | --- | --- | --- | --- | --- | --- |
| BacT/ALERT® (vs. PBP2) | FA (FAN® Aerobic) | 38/39 | 97.4% (86.5 –99.9%) | 100% (79/79) (95.4 –100%) | 100% (92.4 –100%) | 98.8% (93.2 –100%) |
| | FN (FAN® Anaerobic) | 12/12 | 100% (73.5 –100%) | 100% (41/41) (91.4 –100%) | 100% (77.9 –100%) | 100% (93.0 –100%) |
| | SYSTEM (Combined) | 50/52 | 96.2% (86.8–99.5%) | 100% (119/119) (96.9–100%) | 100% (94.2–100%) | 98.3% (94.2–99.8) |
| | | | | | | |
| VersaTREK® (vs. PBP2) | REDOX 1® (aerobic) | 42/43 | 97.7% (87.7 –99.9%) | 97.8% (91/93) (92.4 –99.7%) | 95.4% (85.4 –99.4%) | 98.9% (94.1 –100%) |
| | REDOX 2® (anaerobic) | 9/10 | 90.0% (55.5 –98.9%) | 100% (7/7) (59.0 –100%) | 100% (71.7 –100%) | 87.5% (47.4 –99.7%) |
| | SYSTEM (Combined) | 53/56 | 94.6% (85.1–98.9%) | 100% (97/97) (96.3–100%) | 100% (94.5–100%) | 97.0% (91.5–99.4%) |
| | | | | | | |
| BACTEC™ (vs. PBP2) | Plus Aerobic/F | 29/30 | 96.7% (82.8–99.9%) | 99.0% (101/102) (94.7–100%) | 96.7% (82.8–99.9%) | 99.0% (94.7–100%) |
| | Lytic/10 Anaerobic/F | 18/18 | 100% (81.5–100%) | 98.6% (72/73) (92.6–100%) | 94.7% (74.0–99.9%) | 100% (95.9–100%) |
| | Lytic/10 Anaerobic/F or Standard/10 Aerobic/F | 19/19 | 100% (82.4–100%) | 100% (54/54) (93.4–100%) | 100% (85.4–100%) | 100% (94.6–100%) |
| | PEDS PLUS™/F | 0/0 | N/A | 100% (8/8) (63.1–100%) | N/A | 100% (63.1–100%) |
| | SYSTEM (Combined) | 68/69 | 98.6% (92.2–100%) | 100% (235/235) (98.4–100%) | 100% (95.7–100%) | 99.6% (97.7–100) |
| | SYSTEM (with exclusions*) | 47/48 | 97.9% (88.9–100%) | 98.9% (173/175) (95.9–99.9%) | 95.9% (86.0–99.5%) | 99.4% (96.8–100%) |

*Excludes Lytic/10 Anaerobic/F or Standard/10 Aerobic/F AND PEDS PLUS™/F

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Table 6: Performance of Spectra™ MRSA vs. Traditional Culture, PBP2', or Oxacillin MIC

| Blood Culture System | Blood Culture Bottle Type | #Spectra™ Pos MRSA/ #Total MRSA | MRSA Agreement (95% CI) | Non-MRSA Agreement (95% CI) | Positive Predictive Value (95% CI) | Negative Predictive Value (95% CI) |
| --- | --- | --- | --- | --- | --- | --- |
| All Data | vs. Traditional Culture | 171/177 | 96.6% (92.8–98.7%) | 100% (451/451) (99.2-100%) | 100% (97.9–100%) | 98.7% (97.2–99.5%) |
| | vs. PBP2' | 167/171 | 97.7% (94.1–99.4%) | 99.1% (453/457) (97.8–99.8%) | 97.7% (94.1–99.4%) | 99.1% (97.8–99.8%) |
| | vs. Oxacillin MIC | 171/177 | 96.6% (92.8–98.7%) | 100% (451/451) (99.2-100%) | 100% (97.9–100%) | 98.7% (97.2–99.5%) |
| | | | | | | |
| All (with exclusions*) | vs. Traditional Culture | 152/158 | 96.2% (91.9–98.6%) | 100% (389/389) (99.1–100%) | 100% (97.6–100%) | 98.5% (97.4–99.7%) |
| | vs. PBP2' | 148/152 | 97.4% (93.4–99.3%) | 99.0% (391/395) (97.4–99.7%) | 97.4% (93.4–99.3%) | 99.0% (97.4–99.7%) |
| | vs. Oxacillin MIC | 152/158 | 96.2% (91.9–98.6%) | 100% (389/389) (99.1–100%) | 100% (97.6–100%) | 98.5% (97.4–99.7%) |
| | | | | | | |
| Aerobic Blood Culture Media* | vs. Traditional Culture | 112/117 | 95.7% (90.3–98.6) | 100% (269/269) (98.6–100%) | 100% (96.8–100%) | 98.2% (95.8–99.4%) |
| | vs. PBP2' | 109/112 | 97.3% (92.4–99.4%) | 98.9% (271/274) (96.8–99.8%) | 97.3% (92.4–99.4%) | 98.9% (96.8–99.8%) |
| | vs. Oxacillin MIC | 112/117 | 95.7% (90.3–98.6%) | 100% (269/269) (98.6–100%) | 100% (96.8–100%) | 98.2% (95.8–99.4%) |
| | | | | | | |
| Anaerobic Blood Culture Media* | vs. Traditional Culture | 40/41 | 97.6% (87.1–99.9%) | 100% (120/120) (97.0–100%) | 100% (91.2–100%) | 99.2% (95.5–100%) |
| | vs. PBP2' | 39/40 | 97.5% (86.8–99.9%) | 99.2% (120/121) (95.5–100%) | 97.5% (86.8–99.9%) | 99.2% (95.5–100%) |
| | vs. Oxacillin MIC | 40/41 | 97.6% (87.1–99.9%) | 100% (120/120) (97.0–100%) | 100% (91.2–100%) | 99.2% (95.5–100%) |

*Excludes Lytic/10 Anaerobic/F or Standard/10 Aerobic/F AND PEDS PLUS™/F

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b. Matrix comparison:
Not Applicable

3. Clinical studies:
a. Clinical Sensitivity:
Not Applicable
b. Clinical specificity:
Not Applicable
c. Other clinical supportive data (when a. and b. are not applicable):
Not Applicable

4. Clinical cut-off:
Not Applicable

5. Expected values/Reference range:
Not Applicable

N. Proposed Labeling:
The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10.

O. Conclusion:
The submitted information in this premarket notification is complete and supports a substantial equivalence decision.

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