Thermo Scientific Oxoid Aztreonam/Avibactam Disc (30/20 µg) AZA50

K250789 · Thermo Fisher Scientific (Oxoid Ltd.) · JTN · Jun 12, 2025 · Microbiology

Device Facts

• Record ID: K250789
• Device Name: Thermo Scientific Oxoid Aztreonam/Avibactam Disc (30/20 µg) AZA50
• Applicant: Thermo Fisher Scientific (Oxoid Ltd.)
• Product Code: JTN · Microbiology
• Decision Date: Jun 12, 2025
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 866.1620
• Device Class: Class 2
• Attributes: PCCP

Indications for Use

Thermo Scientific Oxoid Antimicrobial Susceptibility Test Discs are used in the semi-quantitative agar diffusion test method for in vitro susceptibility testing. Used in a diagnostic workflow to aid clinicians in determining potential treatment options for patients suspected of having a microbial infection, these discs are intended to determine susceptibility against microorganisms for which specific drugs have been shown to be active both clinically and in vitro. The Thermo Scientific Oxoid Aztreonam/Avibactam Disc (30/20 μg) AZA50 is intended to determine susceptibility of Enterobacterales to Aztreonam/Avibactam, as recognized by the FDA Susceptibility Test Interpretive Criteria (STIC). The Thermo Scientific Oxoid Aztreonam/Avibactam Disc (30/20 μg) AZA50 demonstrated acceptable performance to determine susceptibility to Aztreonam/Avibactam against the following microorganisms: Enterobacterales (Citrobacter freundii complex, Escherichia coli, Enterobacter cloacae complex, Klebsiella pneumoniae, Klebsiella oxytoca, Serratia marcescens, and Proteus mirabilis)

Device Story

Thermo Scientific Oxoid Aztreonam/Avibactam Disc (30/20 μg) AZA50 is an antimicrobial susceptibility test (AST) disc used in semi-quantitative agar diffusion (Kirby-Bauer) methods. The device consists of a paper disc impregnated with a specific concentration of the antimicrobial agent Aztreonam/Avibactam. In a clinical laboratory setting, the disc is placed on an agar plate inoculated with a patient's microbial isolate. As the drug diffuses into the agar, it inhibits bacterial growth, creating a zone of inhibition. Laboratory technicians measure the diameter of this zone to determine the susceptibility of the microorganism to the drug. Results are interpreted using FDA-recognized Susceptibility Test Interpretive Criteria (STIC) to categorize the organism as susceptible, intermediate, or resistant. This information assists clinicians in selecting appropriate antibiotic therapy for patients with suspected infections.

Clinical Evidence

Performance evaluated using 385 total isolates (310 clinical, 75 challenge) of Enterobacterales. Compared against reference broth microdilution (BMD) per CLSI M07. Results showed 99.2% Category Agreement (CA) with 3 minor errors and no major or very major errors. Reproducibility study (270 data points) showed >95% agreement across disk lots and readers. Quality control testing performed using ATCC strains met acceptance criteria.

Technological Characteristics

Antimicrobial susceptibility test disc; 30/20 μg concentration of Aztreonam/Avibactam; semi-quantitative agar diffusion (Kirby-Bauer) principle; in vitro diagnostic use.

Indications for Use

Indicated for in vitro susceptibility testing of Enterobacterales (Citrobacter freundii complex, Escherichia coli, Enterobacter cloacae complex, Klebsiella pneumoniae, Klebsiella oxytoca, Serratia marcescens, and Proteus mirabilis) to Aztreonam/Avibactam. For prescription use only.

Regulatory Classification

Identification

An antimicrobial susceptibility test disc is a device that consists of antimicrobic-impregnated paper discs used to measure by a disc-agar diffusion technique or a disc-broth elution technique the in vitro susceptibility of most clinically important bacterial pathogens to antimicrobial agents. In the disc-agar diffusion technique, bacterial susceptibility is ascertained by directly measuring the magnitude of a zone of bacterial inhibition around the disc on an agar surface. The disc-broth elution technique is associated with an automated rapid susceptibility test system and employs a fluid medium in which susceptibility is ascertained by photometrically measuring changes in bacterial growth resulting when antimicrobial material is eluted from the disc into the fluid medium. Test results are used to determine the antimicrobial agent of choice in the treatment of bacterial diseases.

Submission Summary (Full Text)

{0}

FDA U.S. FOOD & DRUG ADMINISTRATION

# 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY

ASSAY ONLY

## I Background Information:

A 510(k) Number
K250789

B Applicant
Thermo Fisher Scientific (Oxoid Ltd.)

C Proprietary and Established Names
Thermo Scientific Oxoid Aztreonam/Avibactam Disc (30/20 μg) AZA50

D Regulatory Information
| Product Code(s) | Classification | Regulation Section | Panel |
| --- | --- | --- | --- |
| JTN | Class II | 21 CFR 866.1620 - Antimicrobial Susceptibility Test Disc | MI - Microbiology |

## II Submission/Device Overview:

### A Purpose for Submission:
In this Traditional 510(k) submission, Oxoid Limited (Part of Thermo Scientific) seeks the following:
1. Obtain a substantial equivalence determination for aztreonam/avibactam antimicrobial susceptibility test disk.
2. Establish a Pre-Determined Change Control Plan (PCCP) to address future revisions to device labeling in response to breakpoint changes that are recognized on the FDA STIC webpage.

### B Measurand:
Aztreonam/Avibactam 30/20 μg

### C Type of Test:
Antimicrobial Susceptibility Test Disks

Food and Drug Administration
10903 New Hampshire Avenue
Silver Spring, MD 20993-0002
www.fda.gov

{1}

III Intended Use/Indications for Use:

A Intended Use(s):
See Indications for Use below.

B Indication(s) for Use:
Thermo Scientific Oxoid Antimicrobial Susceptibility Test Discs are used in the semi-quantitative agar diffusion test method for *in vitro* susceptibility testing. Used in a diagnostic workflow to aid clinicians in determining potential treatment options for patients suspected of having a microbial infection, these discs are intended to determine susceptibility against microorganisms for which specific drugs have been shown to be active both clinically and *in vitro*.

The Thermo Scientific Oxoid Aztreonam/Avibactam Disc (30/20 μg) AZA50 is intended to determine susceptibility of Enterobacterales to Aztreonam/Avibactam, as recognized by the FDA Susceptibility Test Interpretive Criteria (STIC). The Thermo Scientific Oxoid Aztreonam/Avibactam Disc (30/20 μg) AZA50 demonstrated acceptable performance to determine susceptibility to Aztreonam/Avibactam against the following microorganisms:

Enterobacterales (*Citrobacter freundii* complex, *Escherichia coli*, *Enterobacter cloacae* complex, *Klebsiella pneumoniae*, *Klebsiella oxytoca*, *Serratia marcescens*, and *Proteus mirabilis*)

C Special Conditions for Use Statement(s):
Rx - For Prescription Use Only

D Special Instrument Requirements:
Not applicable.

IV Device/System Characteristics:

A Device Description:
Thermo Scientific Oxoid Aztreonam/Avibactam Disc (30/20 μg) which is designated with the code AZA50 is a high quality 6mm diameter white filter paper disk that is impregnated with 30/20 μg aztreonam/avibactam. The disks are clearly marked on both sides with AZA50, designating the agent and the drug content. The disks are supplied in plastic cartridges containing 50 disks each. Thermo Scientific Oxoid Aztreonam/Avibactam Disc (30/20 μg) AZA50 is intended to be used for *in vitro* agar diffusion susceptibility testing.

B Principle of Operation:
A suitable therapeutic agent for *in vitro* use can be determined using filter paper disks impregnated with specified concentrations of antimicrobial agents placed on the surface of a suitable test medium. Pure cultures of clinical isolates are inoculated onto the test medium, and

K250789 - Page 2 of 10

{2}

the AST disk placed on the surface. The antibiotic within the disk diffuses into the agar. After incubation, the zones of inhibition around the disks are measured and compared against recognized zone diameter ranges for the specific antimicrobial agent/organism combination under test.

K250789 - Page 3 of 10

V Substantial Equivalence Information:

A Predicate Device Name(s):

Thermo Scientific Oxoid Sulbactam/Durlobactam Disc (10/10 μg) SUD20

B Predicate 510(k) Number(s):

K232276

C Comparison with Predicate(s):

| Device & Predicate Device(s): | Device: K250789 | Predicate: K232276 |
| --- | --- | --- |
| Device Trade Name | Thermo Scientific Oxoid Aztreonam/Avibactam Disc (30/20 μg) AZA50 | Thermo Scientific Oxoid Sulbactam/Durlobactam Disc (10/10 μg) SUD20 |
| General Device Characteristic Similarities | | |
| Intended Use | Antimicrobial Susceptibility Test Discs used in the semi quantitative agar diffusion test method for in vitro susceptibility testing. | Same |
| Test Method | Antimicrobial susceptibility testing using paper disks impregnated with an antimicrobial agent. | Same |
| Methodology | Disk diffusion susceptibility test protocol requires the user to determine categorical interpretations (S/I/R) using the measured zone diameters. | Same |
| Inoculum | Prepared from pure isolated colonies to match the turbidity equivalent of a 0.5 McFarland. | Same |
| Inoculum Method | Dip a sterile swab into the prepared inoculums and streak an appropriate agar plate’s surface three times. Add the disks impregnated with the | Same |

{3}

| Device & Predicate Device(s): | Device: K250789 | Predicate: K232276 |
| --- | --- | --- |
| | antimicrobial agent to the surface of the plate. The temperature, atmospheric conditions and duration of incubation are dependent on the organism tested. | |
| Reading Method | The user will interpret the zone diameters according to established interpretive criteria for the drug. | Same |
| General Device Characteristic Differences | | |
| Antimicrobial Agent | Aztreonam/Avibactam | Sulbactam/Durlobactam |
| Concentration | 30/20 μg | 10/10 μg |

VI Standards/Guidance Documents Referenced:

- CLSI M02-14th ed. Performance Standards for Antimicrobial Disk Susceptibility Tests (March 2024).
- CLSI M100-35th ed. Performance Standards for Antimicrobial Susceptibility Testing (January 2025).

VII Performance Characteristics (if/when applicable):

A Analytical Performance:

1. Precision/Reproducibility:

Reproducibility was conducted at one internal site using 15 organisms, tested in triplicate with two disk lots on three separate days using one lot of media (Mueller Hinton Agar media). Each test was visually read by three independent readers with results blinded, resulting in 270 data points for evaluation (15 organisms x 2 disk lots x 1 media lot x 3 days x 3 independent readers = 270 data points). Colony counts were performed on all isolates.

The reproducibility study included Enterobacterales consisting of the following species: three isolates each of E. cloacae, E. coli, and K. pneumoniae; two isolates each of C. freundii and K. oxytoca; and one isolate each of P. mirabilis and S. marcescens.

Reproducibility was calculated as the percent of results that were within $\pm 3\mathrm{mm}$ difference in zone diameter when comparing each test result with the modal zone diameter value. The reproducibility across disk lots was $>95\%$ and meets the acceptance criteria. Results are shown in Table 1 below.

K250789 - Page 4 of 10

{4}

Table 1: Reproducibility Summary

| Between Disk Lots | | | Across Readers^{1} | | | |
| --- | --- | --- | --- | --- | --- | --- |
| Lot A | Lot B | All Lots | Reader#1 | Reader#2 | Reader#3 | All Readers |
| 98.5%
(133/135) | 100.0%
(135/135) | 99.3%
(268/270) | 98.9%
(89/90) | 98.9%
(89/90) | 100.0%
(90/90) | 99.3%
(268/270) |

¹Two disk lots were read by each reader.

2. Linearity:
Not applicable.

3. Analytical Specificity/Interference:
Not applicable.

4. Assay Reportable Range:
Not applicable.

5. Traceability, Stability, Expected Values (Controls, Calibrators, or Methods):

**Quality Control (QC) Testing:**
The CLSI-recommended quality control (QC) isolate *Klebsiella pneumoniae* ATCC 700603 and CLSI QC isolates *Escherichia coli* ATCC 25922, *Escherichia coli* ATCC 35218, and *Pseudomonas aeruginosa* ATCC 27853 were tested. Two Oxoid disk lots were used and at least 20 replicates per lot per reader were tested. Each test was visually read by at least three independent readers, resulting in 280 Oxoid disk data points. The Oxoid disk QC performance for disk diffusion method was acceptable at >95%. The performance is shown in Table 2 below.

Table 2: Quality Control Performance of Aztreonam/Avibactam Disk (30/20 μg)

| | Zone Diameter in millimeter (mm) | | |
| --- | --- | --- | --- |
| QC Organism | Range | Oxoid Lot A^{1} | Oxoid Lot B^{1} |
| E. coli ATCC 25922
Expected Range: 32–38 mm | 31 | | |
| | 32 | | |
| | 33 | 5 | 6 |
| | 34 | 20 | 18 |
| | 35 | 21 | 22 |
| | 36 | 16 | 13 |
| | 37 | 6 | 9 |
| | 38 | 2 | 2 |
| | 39 | | |
| E. coli ATCC 35218
Expected Range: 31–38 mm | 30 | | |
| | 31 | | 1 |
| | 32 | 2 | 3 |
| | 33 | 3 | 6 |
| | 34 | 22 | 18 |
| | 35 | 27 | 23 |
| | 36 | 14 | 15 |
| | 37 | 1 | 3 |
| | 38 | 1 | 1 |
| | 39 | | |
| | 23 | | |

K250789 - Page 5 of 10

{5}

| | Zone Diameter in millimeter (mm) | | |
| --- | --- | --- | --- |
| QC Organism | Range | Oxoid Lot A¹ | Oxoid Lot B¹ |
| P. aeruginosaATCC 27853 | 24 | 1 | 1 |
| | 25 | 15 | 26 |
| | 26 | 31 | 24 |
| | 27 | 11 | 10 |
| | 28 | 9 | 6 |
| | 29 | 3 | 3 |
| | 30 | | |
| | 31 | | |
| K. pneumoniaeATCC 700603 | 25 | | |
| | 26 | | |
| | 27 | 4 | 6 |
| | 28 | 26 | 23 |
| | 29 | 22 | 20 |
| | 30 | 12 | 12 |
| | 31 | 5 | 8 |
| | 32 | 1 | 1 |
| | 33 | | |

ATCC=American Type Culture Collection
¹Two Oxoid disk lots were tested (lot A and lot B)

Broth micro dilution (BMD) for QC isolates was performed as per CLSI M07 on every day of clinical study to provide assurance of the data quality obtained from the reference method. The QC performance for the reference BMD method was acceptable at >95%. The performance is shown in Table 3 below.

Table 3: Quality Control Performance of Aztreonam/Avibactam by BMD Method

| QC Organism | MIC (μg/mL) | Results |
| --- | --- | --- |
| E. coli ATCC 25922
Expected MIC Range: 0.03/4-0.12/4 μg/mL | 0.016/4 | |
| | 0.03/4 | |
| | 0.06/4 | 13 |
| | 0.12/4 | 1 |
| | 0.25/4 | |
| E. coli ATCC 35218
Expected MIC Range: 0.016/4-0.06/4 μg/mL | 0.008/4 | |
| | 0.016/4 | 5 |
| | 0.03/4 | 7 |
| | 0.06/4 | 2 |
| | 0.12/4 | |
| P. aeruginosa ATCC 27853
Expected MIC Range: 2/4-8/4 μg/mL | 1/4 | |
| | 2/4 | |
| | 4/4 | 11 |
| | 8/4 | 3 |
| | 16/4 | |
| K. pneumoniae ATCC 700603
Expected MIC Range: 0.06/4-0.5/4 μg/mL | 0.03/4 | |
| | 0.06/4 | |
| | 0.12/4 | 11 |

K250789 - Page 6 of 10

{6}

| QC Organism | MIC (μg/mL) | Results |
| --- | --- | --- |
| | 0.25/4 | 3 |
| | 0.5/4 | |
| | 1/4 | |

ATCC=American Type Culture Collection

## Inoculum Density Check:
Colony counts were conducted for all QC and reproducibility isolates, as well as 10% of clinical isolates. All were within the expected range.

## Stability:
A real-time stability study was conducted with the device stored in the storage conditions recommended in the package insert. Three lots of disks were tested throughout the 36-month claimed shelf life, and microbiological and chemical performance results were within the expected range which is acceptable. Stability and storage information is provided in the package insert. The real time stability test is on-going.

6. Detection Limit:
Not applicable.

7. Assay Cut-Off:
Not applicable.

## B Comparison Studies:

1. Method Comparison with Predicate Device:
The qualitative Thermo Scientific Oxoid Aztreonam/Avibactam Disc (30/20 μg) AZA50 disk diffusion results were compared to the qualitative categorical interpretation (S/I/R) based on the minimum inhibitory concentration (MIC) values obtained from reference broth microdilution (BMD) to assess the categorical agreement (CA) and error rates. The study was conducted at two internal testing sites. Seven independent operators participated in reading of test results to mimic multiple testing sites. Testing was performed utilizing Mueller-Hinton agar (MHA) per CLSI M02 guidelines. The reference BMD method was performed per CLSI M07 guidelines.

## Clinical:
Clinical testing was performed using a total of 310 Enterobacterales clinical isolates [C. freundii (30 isolates), E. cloacae (51 isolates), E. coli (70 isolates), K. oxytoca (48 isolates), K. pneumoniae (60 isolates), P. mirabilis (31 isolates), and S. marcescens (20 isolates)].

## Challenge:
Challenge testing was performed at one U.S site and one OUS site using a total of 75 Enterobacterales challenge isolates [C. freundii (11 isolates), E. cloacae (13 isolates), E. coli (13 isolates), K. oxytoca (11 isolates), K. pneumoniae (12 isolates), P. mirabilis (5 isolates), and S. marcescens (10 isolates)].

Performance results for the total 385 clinical and challenge isolates are shown in Table 4.

K250789 - Page 7 of 10

{7}

Table 4: Performance of Thermo Scientific Oxoid Aztreonam/Avibactam Disk vs. Reference BMD Based on Categorical Result Interpretation

| | Total | CA# | %CA | #S | #I | #R | MIN | MAJ | VJM |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Enterobacterales
[Disk Breakpoints (mm): ≥21 (S), 18-20 (I), ≤17 (R)] | | | | | | | | | |
| Clinical | 310 | 308 | 99.4% | 308 | 1 | 1 | 2 | 0 | 0 |
| Challenge | 75 | 74 | 98.7% | 73 | 2 | 0 | 1 | 0 | 0 |
| Combined | 385 | 382 | 99.2% | 381 | 3 | 1 | 3 | 0 | 0 |

CA – Category Agreement
MIN – minor errors
S – Susceptible isolates
MAJ – major errors
I – Intermediate isolates
VMJ – very major errors
R – Resistant isolates

Category Agreement (CA) is when the Thermo Scientific Oxoid disk result interpretation agrees exactly with the MIC result interpretation.

The performance of the Thermo Scientific Oxoid Aztreonam/Avibactam Disc (30/20 μg) AZA50 disk as compared to the MIC for Enterobacterales (Table 4) is acceptable with 99.2% CA. There were three minor errors and no major or very major discrepancies.

## Testing/Reporting Non-Indicated Species:

As required under 511A(b)(2)(C)(ii)(I) of the Federal Food, Drug and Cosmetic Act, the following statement is included as a footnote to the performance table in the device labeling to address testing of non-indicated species:

"Per the FDA-Recognized Susceptibility Test Interpretive Criteria website, the safety and efficacy of antimicrobial drugs, for which antimicrobial susceptibility is tested by this AST device, may or may not have been established in adequate and well-controlled clinical trials for treating clinical infections due to microorganisms outside of those found in the indications and usage in the drug label. The clinical significance of susceptibility information in those instances is unknown. The approved labeling for specific antimicrobial drugs provides the uses for which the antimicrobial drug is approved".

## Resistance Isolates:

A total of 385 clinical and challenge isolates were tested when the Thermo Scientific Oxoid Aztreonam/Avibactam Disc (30/20 μg) AZA50 was compared to the interpretive category based on MIC values for Enterobacterales. However, an insufficient number of resistant isolates were available for testing. To address the lack of resistant strains encountered during the clinical evaluation, the following limitation was added in the device labeling:

"The ability of the Thermo Scientific Oxoid Aztreonam/Avibactam Disc (30/20 μg) AZA50 to detect resistance with the following combination(s) is unknown because an insufficient number of resistant strains were encountered at the time of comparative testing: Aztreonam/Avibactam (30/20 μg) and Enterobacterales group. If such a strain is encountered, it should be submitted to a reference laboratory for further testing".

K250789 - Page 8 of 10

{8}

K250789 - Page 9 of 10

# Resistance Mechanisms in Challenge Isolates:

Challenge isolates of Enterobacteriales harboring various molecular mechanisms of resistance were evaluated with Thermo Scientific Oxoid Aztreonam/Avibactam Disc (30/20 μg) AZA50. The following mechanisms were evaluated: aac(3), aac(6'), AcrF, ACT, ANT, APH(3'), APH(6), ARR, cAmpC, cat, CMY, CRE, CTX, dfrA, DHA, EmrD, ere(A), erm(B), IMP, KdeA, KPC, mcr, mph(A), NDM, OmpK36m OqxA, OXA, qacEdelta1, QepA4, QnrS1, rmtF1, SHV, SME, sul1, sul2, TEM, tet(B), and VIM alleles.

2. Matrix Comparison:
Not applicable.

# C Clinical Studies:

1. Clinical Sensitivity:
Not applicable.

2. Clinical Specificity:
Not applicable.

3. Other Clinical Supportive Data (When 1. and 2. Are Not Applicable):
Not applicable.

# D Clinical Cut-Off:

Not applicable.

# E Expected Values/Reference Range:

The FDA recognized susceptibility interpretive criteria for aztreonam/avibactam are listed in Table 5.

Table 5. FDA Identified Interpretive Criteria for Aztreonam/Avibactam

| | Minimum Inhibitory Concentration (μg/mL)a | | | Zone Diameter (mm)a | | |
| --- | --- | --- | --- | --- | --- | --- |
| Organism | S | I | R | S | I | R |
| Enterobacteriales | ≤4/4 | 8/4 | ≥16/4 | ≥21 | 18-20 | ≤17 |

a FDA STIC Webpage

# VIII Proposed Labeling:

The labeling supports the finding of substantial equivalence for this device.

# IX Conclusion:

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

{9}

To support the implementation of changes to FDA-recognized susceptibility test interpretive criteria (i.e., breakpoints), this submission included a breakpoint change protocol that was reviewed and accepted by FDA. This protocol addresses future revisions to device labeling in response to breakpoint changes that are recognized on the FDA STIC webpage (https://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/ucm410971.htm). The protocol outlined the specific procedures and acceptance criteria that Thermo Scientific Oxoid intends to use to evaluate the Thermo Scientific Oxoid Aztreonam/Avibactam Disc (30/20 μg) AZA50 when revised breakpoints for aztreonam/avibactam are published on the FDA STIC webpage. The breakpoint change protocol included with the submission indicated that if specific criteria are met, Thermo Scientific Oxoid will update the Thermo Scientific Oxoid Aztreonam/Avibactam Disc (30/20 μg) AZA50 device label to include (1) the new breakpoints, (2) an updated performance section after re-evaluation of data in this premarket notification with the new breakpoints, and (3) any new limitations as determined by their evaluation.

K250789 - Page 10 of 10