The case for Fetroja

How Fetroja may help patients

Fetroja demonstrated efficacy in clinical trials involving adult patients with cUTI and HABP/VABP who have infections caused by Gram-negative bacteria, including those at risk for multidrug-resistant (MDR) infections. The safety of Fetroja is consistent with other cephalosporins.1-4

Learn more about Fetroja for patients with cUTI.

Learn more about Fetroja for patients with HABP/VABP.

Fetroja is highly active against MDR, extensively drug-resistant (XDR) and carbapenem-resistant (CR) isolates of Gram-negative pathogens1,5

With an attached catechol side-chain (siderophore), Fetroja uses iron like a “Trojan horse” to actively enter bacterial cells, in addition to passive entry via porin channels.1,4,6

Fetroja has activity in the presence of a variety of CR mechanisms:

  • Fetroja is stable against all classes of β-lactamases (A, B, C, and D), including serine carbapenemases and metallo-β-lactamases1
    • For example, Fetroja is stable against β-lactamases expressed by Acinetobacter baumannii (eg, OXA-23 and OXA-24) and Enterobacterales
  • Fetroja maintains activity in the presence of porin channel deletions1
    • For example, Fetroja is active against pathogens that commonly express porin channel deletions, such as those found in Klebsiella pneumoniae (OmpK35/36) and Pseudomonas aeruginosa (OprD)
  • Fetroja is active against P aeruginosa isolates that are resistant due to efflux pump up-regulation (MexAB-OprM, MexCD-OprJ, MexEF-OprN, and MexXY)1

Learn more about the mechanism of cell entry for Fetroja.

  • Fetroja overcomes the 3 main mechanisms of Gram-negative resistance1,7-11

Fetroja susceptibility testing and verification/validation information for microbiologists*

Order testing supplies

Swipe table for more
Product/link FDA-cleared RUO Catalog/reference number
HardyDisk™ cartridges
Z9431 (1 cartridge)
Z9435 (5 cartridges)
Thermo Scientific™ Oxoid™ Discs
CT1964B
Thermo Scientific™ Sensititre™ MIC Plates†
MDRGN2F
Thermo Scientific™ Sensititre™ MIC Plates with colistin
MDRGNX2F
BD BBL™ Sensi-Disc™ cefiderocol discs
232255
Liofilchem® ComASP® cefiderocol microbroth dilution panel test kits

View ComASP Reading Guide
75009U
Liofilchem® Discs
9266/1 (1 cartridge)
9266 (5 cartridges)
9266/2 (250 discs/canister)

Note: Shionogi is committed to working with manufacturers to make new testing supplies available.

*
Shionogi is not affiliated with the listed entities. No fees or other remuneration have been or will be exchanged for inclusion in this resource, nor does inclusion imply endorsement by or of Shionogi or an entity. This material is for informational purposes only and not intended to provide medical advice; healthcare providers should use their own judgment regarding cefiderocol testing.
†
Please note that this item is temporarily unavailable as of October 1, 2022. Please contact your local Thermo Fisher Scientific™ Microbiology representative for availability.

RUO=Research Use Only.

Learn how to perform verification for Fetroja susceptibility testing in your laboratory

Shionogi has collaborated with institutions to develop a panel of clinical isolates for laboratories to perform verification.

  • Verification: process to determine that an unmodified FDA-cleared/-approved test performs according to manufacturer specifications12
  • Validation: process to confirm that a laboratory-developed or modified FDA-cleared/-approved test method delivers reliable results12

Verify laboratory

Fetroja requires a one-time verification process before clinical samples can be tested. Download the Verification and Validation Resources guide for comprehensive information about laboratory testing of Fetroja.

DOWNLOAD THE GUIDE

Laboratory Specialists, Inc. (LSI)

This panel for cefiderocol is available at no cost to the laboratory through a collaboration with Shionogi. Visit www.labspec.org, email your local representative at , or call (440) 835-4458 to order. A list of pathogens, results, and a reading guide are provided.

OR

CDC Antibiotic Resistance (AR) Isolate Bank

This bank offers a detailed listing of isolates and a panel for cefiderocol the laboratory can order. The CDC provides isolates at no cost to approved institutions. Customers are charged for shipping costs.

ORDER THE CDC AR
ISOLATE PANEL

CLSI verification guideline (M52)

This resource is available for purchase and includes recommendations for commercial microbial identification and antimicrobial susceptibility testing systems to fulfill regulatory or quality assurance requirements.

ACCESS THE CLSI
GUIDELINE (M52)

Resources for testing and reading your results

Disk reading guide for cefiderocol verification using LSI isolates

This guide includes a range of cefiderocol MIC and zone results for both susceptible and non-susceptible Gram-negative isolates. Isolates with a variety of known resistance mechanisms are included.

DOWNLOAD THE
READING GUIDE

Disk summary for cefiderocol verification using LSI isolates

This summary includes results for 40 Gram-negative isolates in the method verification isolate set. Results are based on the CLSI disk diffusion method performed for 5 replicates over multiple days.

DOWNLOAD THE
DISK SUMMARY

MIC summary for cefiderocol verification using LSI isolates

This summary includes results for 40 Gram-negative isolates in the method verification isolate set. Results are based on CLSI broth microdilution performed over multiple days.

DOWNLOAD THE
MIC SUMMARY

Antimicrobial susceptibility testing (AST) can be conducted by either testing in your own laboratory or sending isolates to a reference laboratory

Reference laboratories

A number of institutions have antimicrobial susceptibility testing capabilities for Fetroja and are available to provide testing services on disk and panel-type devices. Contact the reference laboratories listed below for costs and specific information associated with testing.

Swipe table for more
Find a reference laboratory that has antimicrobial capabilities for Fetroja.
State Institution and address Contact information Device offered by laboratory
Alabama The University of Alabama at Birmingham
Fungal Reference Laboratory
W287B | 619 E 19th Street South
Birmingham, AL 35249-7331 		Derek B. Moates, MS, CT(ASCP)CM

Researcher IV, Lab Manager 		Disks
Florida AdventHealth Orlando Jose Alexander, MD, D(ABMM),
FCCM, SM, MB(ASCP)

Medical and Public Health
Microbiologist
Director—Clinical Microbiologist
Microbiology/Virology/Immunology 		BMD/Disks
Georgia Emory University School of Medicine Grady Memorial Hospital Yun “Wayne” Wang, MD, PhD

Professor of Pathology and
Laboratory Medicine, School of
Medicine 		Disks
Maryland Johns Hopkins Medicine Patricia (Trish) J. Simner, PhD,
D(ABMM)

Associate Professor of Pathology
Director of Bacteriology and
Infectious Disease Sequencing
Laboratories
Department of Pathology 		Disks
Minnesota Mayo Clinic Laboratories
3050 Superior Dr NW
Rochester, MN 55901 		Mayo Clinic
Phone: (800) 533-1710
 Disks
Nevada University Medical Center of Southern Nevada
1800 W. Charleston Blvd
Las Vegas, NV 89102 		Clarinda C. Tagapan, MT (AMT)
Clinical Laboratory Supervisor
(Microbiology) Laboratory Services

Phone: (702) 207-8392 		Disks
New Jersey Atlantic Health
Atlantic Consolidated Laboratory
100 The American Rd Ste 118
Morris Plains, NJ 07950 		Mary Fitzgerald, MPH, MLS(ASCP)CM

Microbiology Supervisor 		Disks
Ohio Laboratory Specialists, Inc.
26214 Center Ridge Rd
Westlake, OH 44145 		Phone: (440) 835-4458
 Broth microdilution with ID-CAMHB
Tennessee Vanderbilt University Medical Center
1301 Medical Center Dr, TVC 4526
Nashville, TN 37232 		Pamela Foster

Phone: (615) 875-3210 		Disks
Sensititre™ Panels
Utah University of Utah School of Medicine Mark Fisher, PhD, D(ABMM)

Associate Professor of Pathology
Medical Director, Bacteriology and
Special Microbiology 		Broth microdilution
Wisconsin Froedtert and the Medical College of Wisconsin Nate Ledeboer, PhD

Professor, Pathology & Laboratory Medicine
Medical Director, Clinical Microbiology
Medical Director, Molecular Diagnostics 		Disks
Sensititre™ Panels

Note: Thermo Fisher™ Scientific is able to perform susceptibility testing on isolates. However, it should be noted that Thermo Fisher™ Scientific is not a CLIA-certified laboratory and there is a fee for testing. For more information, please email or contact technical support at .

Additional Fetroja antimicrobial resources

Fetroja microbiologist laboratory brochure

This brochure outlines the distinct profile for Fetroja: its mechanism of cell entry, how it overcomes 3 major mechanisms of carbapenem resistance, and its in vitro activity against challenging pathogens.

DOWNLOAD THE
MICROBIOLOGIST
LABORATORY BROCHURE

Surveillance of clinical isolates for Fetroja

Get an overview of in vitro susceptibility rates of clinical strains of Gram-negative bacteria, including Enterobacterales, P aeruginosa, A baumannii complex, and Stenotrophomonas maltophilia, to Fetroja, compared with commonly used β-lactams/β-lactamase inhibitors and colistin.

DOWNLOAD THE
5-YEAR GLOBAL
SURVEILLANCE STUDY

Karlowsky 2022 AAC: SIDERO-WT surveillance studies (2014 to 2019)

The Karlowsky paper reports on the in vitro susceptibility results of more than 40,000 clinical isolates of multiple pathogens to Fetroja vs comparators over a 5-year period.

READ THE FULL PAPER

The full Fetroja story

Get an overview of Fetroja, including information about its structure, mechanism of action, antimicrobial activity, and more.

DOWNLOAD THE
FETROJA OVERVIEW

CLSI resources

Verification guideline (M52):
This resource is available for purchase and includes recommendations for commercial microbial identification and antimicrobial susceptibility testing systems to fulfill regulatory or quality assurance requirements.

ACCESS THE CLSI
GUIDELINE (M52)

Antimicrobial susceptibility testing guide (M100):
Portions of this resource may require registration or purchase. It outlines laboratory performance standards, including Fetroja broth preparation. It also assists with reading and interpreting broth microdilution endpoints, including if trailing occurs.

ACCESS THE CLSI
GUIDELINE (M100)

Pathogen-specific resources for Fetroja

Interested in the activity of Fetroja against specific pathogens? The P aeruginosa brochure outlines the activity of Fetroja in vitro and in clinical infections.

DOWNLOAD THE
P AERUGINOSA
BROCHURE

The A baumannii complex brochure details the in vitro activity of Fetroja as well as the clinical activity in patients with HABP/VABP in the APEKS-NP Phase 3 study.

DOWNLOAD THE
A BAUMANNII
COMPLEX BROCHURE

In vitro activity does not necessarily correlate with clinical efficacy.

FDA and CLSI breakpoints for Fetroja

Below are the FDA and CLSI breakpoints for Fetroja. Breakpoints may differ between various organizations and health authorities for many reasons, including use of different databases, differences in data interpretation, and public health policies.13

How to interpret results

Swipe table for more
Find FDA breakpoints for Fetroja.
FDA13,14 Minimum inhibitory concentration (µg/mL) Zone diameter (mm)a
Pathogen Susceptible Intermediate Resistant Susceptible Intermediate Resistant
Enterobacteralesb,c ≤4 8 ≥16 ≥16 9-15 ≤8
Pseudomonas aeruginosa ≤1 2 ≥4 ≥22 13-21 ≤12
Acinetobacter baumannii complex ≤1 2 ≥4 ≥19 12-18 ≤11
a
For disk diffusion, paper disks impregnated with 30 µg cefiderocol.14
b
Clinical efficacy was shown for Escherichia coli, K pneumoniae, Proteus mirabilis, and Enterobacter cloacae complex in patients with cUTI.14
c
Clinical efficacy was shown for E coli, K pneumoniae, P mirabilis, E cloacae complex, and Serratia marcescens in patients with HABP/VABP.14
Swipe table for more
Find CLSI breakpoints for Fetroja.
CLSI13* Minimum inhibitory concentration (µg/mL) Zone diameter (mm)a
Pathogen Susceptible Intermediate Resistant Susceptible Intermediate Resistant
Enterobacterales ≤4 8 ≥16 ≥16 9-15 ≤8
Pseudomonas aeruginosa ≤4 8 ≥16 ≥18 13-17 ≤12
Acinetobacter baumannii complex ≤4 8 ≥16 ≥15b - -
Stenotrophomonas maltophiliac ≤1 - - ≥15 - -
*
The accuracy and reproducibility of cefiderocol testing results by disk diffusion and broth microdilution are markedly affected by iron concentration and inoculum preparation and may vary by disk and media manufacturer. Depending on the type of variance observed, false-resistant or false-susceptible results may occur. Testing subsequent isolates is encouraged. Discussion with prescribers and antimicrobial stewardship members regarding the potential for inaccuracies is recommended.
Breakpoints are based on a dosage regimen of 2 grams every 8 hours administered over 3 hours.13
a
Disk content for cefiderocol is 30 µg.13
b
Disk diffusion zone diameters ≤14 mm should not be interpreted or reported because zone diameters ≤14 mm occur with resistant, intermediate, and susceptible isolates. For isolates with zone diameters ≤14 mm, do not report cefiderocol without performing an MIC test.13
c
Breakpoints are based on PK/PD properties, MIC distributions, and limited clinical data.13

The FDA and CLSI MIC breakpoints charts both include data on Enterobacterales, P aeruginosa, and A baumannii complex. The CLSI MIC breakpoints chart also includes S maltophilia.

DOWNLOAD THE FDA & CLSI MIC BREAKPOINTS CHARTS

Fetroja microbiologist FAQs

  • Verification: process to determine that an unmodified FDA-cleared/-approved test performs according to the specifications set forth by the manufacturer12
  • Validation: process used to confirm with objective evidence that a laboratory-developed or modified FDA-cleared/-approved test method or instrument system delivers reliable results12

Shionogi has collaborated with Laboratory Specialists, Inc. (LSI) to develop a panel of isolates for laboratories to perform verification/validation. This panel is available at no cost to the laboratory. To request isolates:

  • Download the form at the LSI website, www.labspec.org. The form can be found by selecting “AST Method Verification Isolates for New Agents” from the home page. Then, select “request form”
  • Fill out the form to request the cefiderocol panel
  • Fax the form to (440) 835-5786 or email it to
  • For additional information, contact LSI at or (440) 835-4458

Shionogi has collaborated with the CDC & FDA AR Isolate Bank (https://www.cdc.gov/drugresistance/resistance-bank/) to develop a panel of isolates for laboratories to perform validation. For a detailed listing of isolates and to order the panel, visit https://www.cdc.gov/abcs/pathogens/isolatebank/index.html. The CDC provides isolates at no cost to approved institutions. Customers are charged for shipping costs.

As the timeline for the development of the AR Isolate Bank Cefiderocol Validation Panel was unclear due to the pandemic, Shionogi sought to develop a panel as soon as possible in collaboration with Laboratory Specialists, Inc.

The CDC & FDA AR Bank Isolate Panel only includes pathogens that are on List 1, while the LSI panel includes additional isolates (eg, S maltophilia). List 1 pathogens refer to pathogens for which the FDA determined cefiderocol has demonstrated clinical efficacy and provided breakpoints.

A laboratory may use either panel or combination of isolates to validate testing in their laboratory.

Unlike an MIC, which is an objective value, breakpoints are subjective. They are known as “interpretive criteria” in determining susceptible, intermediate, or resistant classifications. Breakpoint setting integrates MICs, pharmacokinetics/pharmacodynamics, and clinical outcomes. It is not uncommon for different agencies to have different breakpoints for the same antibiotic.13,15

The CLSI has approved Fetroja breakpoints of ≤4 (susceptible), 8 (intermediate), and ≥16 (resistant) μg/mL for Enterobacterales, P aeruginosa, A baumannii complex, and ≤1 µg/mL for S maltophilia. In 2018, investigational breakpoints were approved by CLSI, prior to the approval of cefiderocol based on in vitro and preclinical in vivo PK/PD data.13,15

FDA-identified breakpoints for Fetroja are ≤4 (susceptible), 8 (intermediate), and ≥16 (resistant) μg/mL for Enterobacterales, and ≤1 (susceptible), 2 (intermediate), and ≥4 (resistant) μg/mL for P aeruginosa and A baumannii complex.14

Contact us

Have questions regarding verification, testing, or surveillance data?

Our team is here to help. Please contact us at (800) 849-9707, , or https://www.shionogi.com/us/en/innovation/medical-information.html.