ETEST FOR GEMIFLOXACIN

K042390 · Ab Biodisk · JWY · Nov 19, 2004 · Microbiology

Device Facts

• Record ID: K042390
• Device Name: ETEST FOR GEMIFLOXACIN
• Applicant: Ab Biodisk
• Product Code: JWY · Microbiology
• Decision Date: Nov 19, 2004
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 866.1640
• Device Class: Class 2

Indications for Use

Etest® is a quantitative technique for determining the antimicrobial susceptibility testing of both non-fastidious Gram-negative and Gram positive aerobic bacteria such as Enterobacteriaceae, Pseudomonas, Staphylococcus and Enterococcus species and fastidious bacteria, such as anaerobes N. gonorrhoeae, S. pneumoniae, Streptococcus and Haemophilus species. It uses a predefined antibiotic gradient to determine the Minimum Inhibitory Concentration (MIC) in µg/mL of different antimicrobial agents against microorganisms as tested on agar media using overnight incubation.

Device Story

Etest® is a manual antimicrobial susceptibility test (AST) system. It consists of a 5mm x 60mm inert plastic strip containing a predefined exponential gradient of dried, stabilized antibiotic. The strip is applied to an inoculated agar plate; the antibiotic diffuses into the agar, creating a concentration gradient. After overnight incubation, a symmetrical inhibition ellipse forms around the strip. The clinician reads the Minimum Inhibitory Concentration (MIC) at the point where the ellipse edge intersects the strip. The device provides quantitative MIC values, which are used by healthcare providers to determine bacterial susceptibility to gemifloxacin, aiding in the selection of appropriate antimicrobial therapy. It is intended for use in clinical laboratory settings.

Clinical Evidence

No clinical data provided. Substantial equivalence is based on bench testing performance characteristics for the determination of MIC values for Gemifloxacin against specified bacterial isolates.

Technological Characteristics

Quantitative antimicrobial susceptibility test strip; predefined antibiotic gradient; manual application to agar media; overnight incubation; visual MIC determination via growth inhibition ellipse intersection.

Indications for Use

Indicated for testing Enterobacteriaceae, S. pneumoniae, and H. influenzae for susceptibility to gemifloxacin (0.002 – 32 µg/mL). For prescription use.

Regulatory Classification

Identification

An antimicrobial susceptibility test powder is a device that consists of an antimicrobial drug powder packaged in vials in specified amounts and intended for use in clinical laboratories for determining in vitro susceptibility of bacterial pathogens to these therapeutic agents. Test results are used to determine the antimicrobial agent of choice in the treatment of bacterial diseases.

Submission Summary (Full Text)

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510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION
DECISION SUMMARY
DEVICE ONLY TEMPLATE

A. 510(k) Number:
k042390

B. Purpose for Submission:
Addition of gemifloxacin to the Etest® strip

C. Analyte:
Gemifloxacin 0.002 – 32 µg/mL

D. Type of Test:
Quantitative AST growth based detection

E. Applicant:
AB BIODISK

F. Proprietary and Established Names:
Etest® for Antimicrobial Susceptibility Testing

G. Regulatory Information:
1. Regulation section:
866.1640 Antimicrobial Susceptibility Test
2. Classification:
II
3. Product Code:
JWY - Manual Antimicrobial Test Systems
4. Panel:
83 Microbiology

H. Intended Use:
1. Intended use(s):
Etest® is a quantitative technique for determining the antimicrobial susceptibility testing of both non-fastidious Gram-negative and Gram positive aerobic bacteria such as Enterobacteriaceae, Pseudomonas, Staphylococcus and Enterococcus species and fastidious bacteria, such as anaerobes N. gonorrhoeae, S. pneumoniae, Streptococcus and Haemophilus species. It uses a predefined antibiotic gradient to determine the Minimum Inhibitory Concentration (MIC) in µg/mL of different antimicrobial agents against microorganisms as tested on agar media using overnight incubation.
2. Indication(s) for use:
This submission is for the addition of the antibiotic gemifloxacin at concentrations of 0.002 – 32 µg/mL to the Etest® strip for testing Enterobacteriaceae, S. pneumoniae and H. influenzae.
3. Special condition for use statement(s):
For prescription use
4. Special instrument Requirements:
Manual readings only

I. Device Description:

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Etest® consists of a thin, inert and non-porous plastic strip, 5mm wide and 60 mm long. One side of the strip carries a two-letter code designating the identity of the antibiotic and is calibrated with MIC values in terms of ug/mL. A predefined exponential gradient of the dried and stabilized antibiotic covers a continuous concentration range across 15 two-fold dilutions of a conventional MIC method.

## J. Substantial Equivalence Information:

1. Predicate device name(s):
Etest®
2. Predicate K number(s):
K971694
3. Comparison with predicate:
| Similarities | | |
| --- | --- | --- |
| Item | Device | Predicate |
| Intended Use | Quantitative susceptibility to antimicrobial agents | Same |
| Incubation | 35° | Same |
| Inoculation | Isolated colonies from culture used | Same |
| Result | MIC | MIC |
| Differences | | |
| Item | Device | Predicate |
| Antibiotic | Gemifloxacin | Ceftazidime |

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

"Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems; Guidance for Industry and FDA"; NCCLS M7 (M100-S14)

"Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically; Approved Standard."

## L. Test Principle:

The Etest® gradient technology is based on a combination of the concepts of dilution and diffusion test methods for susceptibility testing. Etest® directly quantifies antimicrobial susceptibility in terms of discrete MIC values. When the Etest® strip is applied to an inoculated agar plate, the antibiotic is immediately released from the plastic surface into the agar. A predefined, continuous gradient of antibiotic concentrations is created and maintained directly underneath the strip. After incubation whereby bacterial growth becomes visible, a symmetrical inhibition ellipse centered along the strip will be seen. The MIC value in ug/mL is read where the ellipse edge intersects the strip. Since Etest® generates MIC values which fall between two-fold dilutions for interpretation, the MIC value read must be recorded to the next two-fold dilution.

## M. Performance Characteristics (if/when applicable):

1. Analytical performance:

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a. Precision/Reproducibility:
Twenty-five gram-negative on-scale organisms were tested one time at three sites with >95% reproducibility. Ten isolates of S. pneumoniae and 10 isolates of H. influenzae were also evaluated at three sites three times to determine site to site reproducibility demonstrating >95% reproducibility.

b. Linearity/assay reportable range:
Not applicable

c. Traceability (controls, calibrators, or method):
The recommended Quality Control (QC) isolates were tested on every test occasion with the reference method and the Etest®. The reference method QC results were in range for every day tested. The Etest® was tested a sufficient number of times to demonstrate that the system can produce QC results in the recommended range.

Quality Control Data for Enterobacteriaceae

| ORGANISM | conc. | Reference | | Etest® | | |
| --- | --- | --- | --- | --- | --- | --- |
| | | | | | | |
| E. coli
ATCC 25922
Expected Result:
0.004 – 0.016 μg/mL | 0.004 | | 10 | | 8 | |
| | 0.008 | | 46 | | 51 | |
| | 0.016 | | 6 | | 3 | |
| | | | | | | |
| | | | | | | |
| E. faecalis
ATCC 29212
Expected Result:
0.016 – 0.125 μg/mL | 0.016 | | | | | |
| | 0.032 | | 3 | | 8 | |
| | 0.064 | | 45 | | 40 | |
| | 0.125 | | 13 | | 13 | |
| | | | | | | |

Quality Control Data for S. pneumoniae

| ORGANISM | conc. | Reference | | | Etest® | | |
| --- | --- | --- | --- | --- | --- | --- | --- |
| | | | | | | | |
| S. pneumoniae
ATCC 49619
Expected Result:
0.008 – 0.032 μg/mL | 0.008 | | 10 | | | 12 | |
| | 0.016 | | 35 | | | 21 | |
| | 0.032 | | 15 | | | 27 | |
| | | | | | | | |
| | | | | | | | |

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Quality Control Data for *H. influenzae*

| ORGANISM | conc. | Reference | | | Etest® | | |
| --- | --- | --- | --- | --- | --- | --- | --- |
| | | | | | | | |
| H. influenzae | 0.002 | | | | | | |
| ATCC 49247 | 0.004 | | | | | 41 | |
| Expected Result: | 0.008 | | 61 | | | 21 | |
| 0.002 – 0.008 μg/mL | | | | | | | |
| | | | | | | | |

A 0.5 McFarland is used to determine the correct inoculum. Colony counts were performed periodically at each site to demonstrate that the inoculum procedure results were in the expected CFU/ml. For *Enterobacteriaceae*, the expected range of QC colony count is from 0.6 – 1.1 x 10⁸ CFU/ml, precision colony count is 1.0 x 10⁸ CFU/ml, and clinical/stock colony count is 0.5 x 10⁸ CFU/ml. For *S. pneumoniae*, the expected range of QC colony count is 0.3 x 10⁸ CFU/ml and clinical/stock colony count is 1.0 x 10⁸ CFU/ml. The expected range of *H. influenzae* colony count is as follows: QC is 0.3 x 10⁸ and clinical/stock is 2.0 x 10⁸ CFU/ml.

The no growth rate is <10% for all organisms tested.

d. Detection limit:
Not Applicable

e. Analytical specificity:
Not applicable

f. Assay cut-off:
Not applicable

2. Comparison studies:

a. Method comparison with predicate device:
Clinical testing was performed at three sites and compared to a recommended NCCLS method which would be the agar dilution for the *Enterobacteriaceae* group and broth dilution for the comparison of *S. pneumoniae* and the *H. influenzae*. Etest® was set up on Mueller Hinton (MH) for *Enterobacteriaceae*; Haemophilus Test Medium (HTM) agar for *H. influenzae*; and 5% sheep blood for *S. pneumoniae*. For the *Streptococcus pneumoniae* isolates, broth reference panels supplemented with 2-5% lysed horse blood were prepared according to the recommendations of the NCCLS. *H. influenzae* reference panels were set up in a HTM media. The *S. pneumoniae* and *H. influenzae* Etests® were incubated in CO² and compared to the reference broth dilution method which was not incubated in CO² as recommended by NCCLS. The clinical testing included both fresh clinical isolates and stock isolates along with a challenge set with known results. A comparison was provided to the reference method with the following agreement.

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GN Accuracy MIC summary for Enterobacteriaceae

| | EA Tot | EA N | EA % | Eval EA Tot | Eval EA N | Eval EA % | CA N | CA % | #R | min | maj | vmj |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Clinical | 294 | 291 | 99 | 278 | 275 | 98.9 | 289 | 98.3 | 29 | 5 | 0 | 0 |
| Challenge | 75 | 75 | 100 | 63 | 63 | 100 | 72 | 96.2 | 32 | 3 | 0 | 0 |
| Combined | 369 | 366 | 99.2 | 341 | 338 | 99.1 | 361 | 97.8 | 61 | 8 | 0 | 0 |

GP Accuracy MIC Summary for S. pneumoniae

| | EA Tot | EA N | EA % | Eval EA Tot | Eval EA N | Eval EA % | CA N | CA % | #R | min | maj | vmj |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Clinical | 353 | 349 | 98.9 | 353 | 349 | 98.9 | 353 | 100 | 0 | 0 | 0 | 0 |
| Challenge | 58 | 58 | 100 | 58 | 58 | 100 | 54 | 93.1 | 2 | 4 | 0 | 0 |
| Combined | 411 | 407 | 99 | 411 | 407 | 99.0 | 407 | 99.0 | 2 | 4 | 0 | 0 |

GN Accuracy MIC Summary for H. influenzae

| | EA Tot | EA N | EA % | Eval EA Tot | Eval EA N | Eval EA % | CA N | CA % | NS | min | maj | vmj |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Clinical | 225 | 222 | 98.7 | 191 | 188 | 98.4 | 225 | 100 | 0 | N/A | N/A | N/A |
| Challenge | 52 | 51 | 98.1 | 44 | 43 | 97.7 | 52 | 100 | 1 | N/A | N/A | N/A |
| Combined | 277 | 273 | 98.6 | 235 | 231 | 98.3 | 277 | 100 | 1 | N/A | N/A | N/A |

EA-Essential Agreement
CA-Category Agreement
R-resistant isolates
NS - Not susceptible isolates

maj-major discrepancies
vmj-very major discrepancies
min- minor discrepancies

Essential agreement (EA) is when the Etest® agrees with the reference test panel results exactly or within one doubling dilution of the reference method. Category agreement (CA) is when the Etest® panel result interpretation agrees exactly with the reference panel result interpretation. All Etest® results were rounded up to the nearest two-fold dilution.

There were no vmj or maj errors for the Enterobacteriaceae group. There were 8 min errors with an acceptable min error rate of $2.2\%$ . All min errors were in essential agreement.

For S. pneumoniae, there were 4 min errors with a min error rate of $1.0\%$ and no vmj or maj errors. The min error rate was acceptable. A limitation statement has been added to the S. pneumoniae group to address the insufficient number of resistant organisms tested.

Only susceptible category exists for $H.$ influenzae. NCCLS standard's recommendation is to repeat "not susceptible" results.

There appears to be a slight trend with the Enterobacteriaceae where the reference method is more resistant than the Etest® but still in essential agreement. This was not observed in the quality control results. There is no trending observed with the accuracy studies for S. pneumoniae however, the QC results showed a slight trending with the reference method more susceptible than the test method. Slight trending was

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also observed in *H. influenzae* where the reference was more resistant than the test method. This was also reflected in the quality control results.

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:
Enterobacteriaceae ≤0.25(S), 0.5(I), ≥1(R)
S. pneumoniae ≤0.12(S), 0.25(I), ≥0.5(R)
H. influenzae ≤0.12(S)
The expected value range, interpretative criteria and QC are the same as recommended by NCCLS and FDA. All values will be included in the package insert.

For *S. pneumoniae* isolates, the ability of the Etest® system to detect resistance to gemifloxacin in *S. pneumoniae* organisms is unknown because resistant organisms were not available at the time of comparative testing.

For *H. influenzae* isolates, the current absence of data on resistant strains precludes defining any results other than “Susceptible”. Strains yielding MIC results suggestive of a “non-susceptible” category should be submitted to a reference laboratory for further testing.

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