Training Example: Fetroja (cefiderocol) | Shionogi – Review the Data, Give Your Score & Compare to the Real AI Evaluation

The first cephalosporin to have an indication for Acinetobacter baumannii complex1

[H1]
For HABP/VABP and cUTI proven or strongly suspected to be caused by susceptible bacteria1
OUTSMART RESISTANCE
[H2] Like a Trojan horse, Fetroja outsmarts hard-to-treat pathogens by using iron to gain cell entry1-3

[IMG: Fetroja Trojan horse and warrior campaign imagery]

Watch a video to see how Fetroja works

Learn about Fetroja clinical efficacy and safety data

See real-world evidence from the PROVE study

Access Fetroja susceptibility testing resources

[H1] Microbiologist diagnostic toolkit

See updated Fetroja testing options

[H2]
The case for Fetroja
[H3] 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.

[H3] 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

[H2] Fetroja susceptibility testing and verification/validation information for microbiologists*

[H3]
Order testing supplies
Swipe table for more

Product/link
FDA-cleared
RUO
Catalog/reference number

HardyDisk™ cartridges
Now FDA-cleared with updated labeling to include breakpoints for S maltophilia

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 January 2025. Please contact your local Thermo Fisher Scientific™ Microbiology representative for availability.

RUO=Research Use Only.

[H3]
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

[H3] 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

[H3] 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 info@labspec.org, or call (440) 835-4458 to order. A list of pathogens, results, and a reading guide are provided.

OR

[H3] 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

[H3] Clinical and Laboratory Standards Institute (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)

[H3] Resources for testing and reading your results

[H3] 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 THEREADING GUIDE

[H3] Disk summary for cefiderocol verification using LSI isolates

This summary includes results for 35 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 THEDISK SUMMARY

[H3] MIC summary for cefiderocol verification using LSI
isolates

This summary includes results for 35 Gram-negative
isolates in the method verification isolate set. Results are based on CLSI broth
microdilution performed over multiple days.

DOWNLOAD THEMIC SUMMARY

[H3] 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
dmoates@uabmc.edu
Researcher IV, Lab Manager

Disks

Florida
AdventHealth Orlando

Jose Alexander, MD, D(ABMM),
FCCM, SM, MB(ASCP)
jose.alexander@adventhealth.com
Medical and Public Health
Microbiologist
Director—Clinical Microbiologist
Microbiology/Virology/Immunology

Broth microdilution/Disks

Georgia

Emory University School of Medicine Grady Memorial Hospital

Yun “Wayne” Wang, MD, PhD
yfwang@emory.edu
Professor of Pathology and
Laboratory Medicine, School of
Medicine

Disks

Maryland

Johns Hopkins Medicine

Andrew Clark, PhD, D(ABMM)
aclar126@jh.edu
Assistant Professor of Pathology
Director of Bacteriology
Department of Pathology
Johns Hopkins Medicine

Disks

Minnesota

Mayo Clinic Laboratories
3050 Superior Dr NW
Rochester, MN 55901

Mayo Clinic
Phone: (800) 533-1710
mcl@mayo.edu

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
clarinda.tagapan@umcsn.com
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
mary.fitzgerald@atlantichealth.org
Microbiology Supervisor

Disks

Ohio

Laboratory Specialists, Inc.
26214 Center Ridge Rd
Westlake, OH 44145

Phone: (440) 835-4458
info@labspec.org

Broth microdilution with ID-CAMHB

Tennessee

Vanderbilt University Medical Center
1301 Medical Center Dr, TVC 4526
Nashville, TN 37232

Pamela Foster
pamela.j.foster@vumc.org
Phone: (615) 875-3210

Disks
Sensititre™ Panels

Utah

University of Utah School of Medicine

Mark Fisher, PhD, D(ABMM)
mark.fisher@aruplab.com
Professor of Pathology
Medical Director, Bacteriology and
Special Microbiology

Broth microdilution

Wisconsin

Froedtert and the Medical College of Wisconsin

Nate Ledeboer, PhD
nledeboe@mcw.edu
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 isolatetesting@thermofisher.com or contact technical support at USCLEtechsupport@thermofisher.com.

[H2] Additional Fetroja antimicrobial resources

[H3] 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

[H3] 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 GLOBAL
SURVEILLANCE STUDY

[H3] 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

[H3] 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

[H3] 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)

[H3] ComASP cefiderocol in comparison to CLSI broth microdilution testing

This study assessed the reliability of ComASP to CLSI broth microdilution by testing cefiderocol against relevant clinical isolates and comparing the results.

VIEW THE FULL STUDY

[H3] 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.

[H3] 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

8d

≥16

≥16

9-15d

≤8

Pseudomonas aeruginosa

≤1

2

≥4

≥22

13-21

≤12

Acinetobacter baumannii complex

≤1

2

≥4

≥19

12-18

≤11

Stenotrophomonas maltophilia

≤1e

-

-

≥17

-

-

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, E cloacae complex, and
Serratia marcescens in patients with HABP/VABP.14

d
Designation for agents that have the potential to concentrate in the urine.13

e
Breakpoints are based on PK/PD properties, MIC distributions, and limited clinical data.13

Swipe table for more

Find CLSI breakpoints for Fetroja.

CLSI5,13,14*
Minimum inhibitory concentration (µg/mL)
Zone diameter (mm)a

Pathogen
Susceptible
Intermediate
Resistant
Susceptible
Intermediate
Resistant

Enterobacterales
≤4

8b

≥16

≥16

9-15b

≤8

Pseudomonas aeruginosa

≤4

8b

≥16

≥18

13-17b

≤12

Acinetobacter baumannii complex

≤4

8

≥16

≥15c

-

-

Stenotrophomonas maltophiliad

≤1

-

>1

≥17

-

≤14

*
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.14

b
Designation for agents that have the potential to concentrate in the urine.13

c
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 cefidero

[H1] Downloadable resources

[H3] View the resources below to learn more about Fetroja

[IMG: Image of in vitro susceptibility data]

[H3] Surveillance in vitro susceptibility data
See how Fetroja compares with selected antibacterial agents in a surveillance study. The data are derived from clinical isolates of Gram-negative bacteria collected in North America and Europe.
DOWNLOAD

[IMG: Image of microbiological information brochure]

[H3] A closer look into Fetroja
Find out more about key microbiological information for Fetroja, such as structure and mechanism of cell entry. This brochure also includes information about testing methods for Fetroja.
DOWNLOAD

[IMG: Image of Fetroja dosing and administration document]

[H3] Fetroja dosing and administration
View dosing and administration information for Fetroja. Also, learn about storage requirements for the product.
DOWNLOAD

[IMG: Image of Fetroja product fact sheet]

[H3] Fetroja product fact sheet
Get essential information about Fetroja, including how it’s supplied, storage, and handling, as well as how to order the product.
DOWNLOAD

[H2] Educational speaker program

[H3] Contact a representative for information about attending a live or virtual Fetroja speaker program

FIND OUT MORE

[H1] Emerging carbapenem resistance in Gram-negative pathogens threatens to further limit antibiotic treatment options1,2

[H2] Key resistance facts for high-priority pathogens

Enterobacterales

Metallo-β-lactamases (MBLs) are on the rise3

In 2021, 20.4% of CRE infections in the US were caused by MBL-producing isolates vs ~4% in 2019a

Pseudomonas aeruginosa

Exhibits intrinsic and adaptive resistance4

Mechanisms include the overexpression of efflux pump MexAB-OprM, AmpC, and deleted porin channel OprD

Acinetobacter baumannii

Co-infection threat5,6

1 out of every 3 to 5 A baumannii complex infections is polymicrobial, often with other Gram-negative pathogens
A baumannii may protect co-infecting pathogens from carbapenem therapy

Stenotrophomonas maltophilia

Intrinsic β-lactam resistance via MBL7
Chromosomally encoded metallo-β-lactamase (L1) and serine cephalosporinase (L2) confer resistance to β-lactams and carbapenems

a
Based on a surveillance study that included 27,834 Enterobacterales isolates collected from 74 US medical centers in 2019-2021.3

CRE=carbapenem-resistant Enterobacterales.

[H2] Carbapenem non-susceptible pathogen distribution8

The most prevalent carbapenem-non-susceptible pathogens seen in US inpatients are Pseudomonas spp, 38%;
Stenotrophomonas maltophilia, 31%; Enterobacterales, 21% and Acinetobacter spp, 9%; Other, 1%

Based on the Premier Healthcare Database: Adult, non-cystic fibrosis patients in the inpatient setting treated with antibiotics from 2021 and 2022 with carbapenem non-susceptible Gram-negative pathogen cultures.

[H2] Frequency of carbapenem-resistant (CR) Enterobacterales isolates producing MBLs in the US3

Metallo-β-lactamases (MBLs) are on the rise. In 2021, 20.4% of carbapenem-resistant Enterobacterales (CRE) infections were caused by MBL-producing isolates vs ~4% in 2019

Based on 27,834 Enterobacterales isolates collected from 74 US medical centers in 2019-2021. CRE (n=261) were screened for carbapenemase (CPE) genes by whole-genome sequencing.

[H4]
Carbapenem resistance in Gram-negative pathogens requires a thoughtful antimicrobial approach1,2