TY - JOUR
T1 - Treatment of carbapenem-resistant Pseudomonas aeruginosa infections
T2 - a case for cefiderocol
AU - Canton, Rafael
AU - Doi, Yohei
AU - Simner, Patricia J.
N1 - Funding Information:
Editorial and medical writing support was provided by Adrienn Kis and Joanne Shrewsbury-Gee, Highfield, Oxford, United Kingdom. This support was sponsored by Shionogi & Co., Ltd., Osaka, Japan.
Funding Information:
This paper was not funded. Editorial and medical writing support was provided by Adrienn Kis and Joanne Shrewsbury-Gee, Highfield, Oxford, United Kingdom. This support was sponsored by Shionogi & Co., Ltd., Osaka, Japan.
Funding Information:
R Canton has participated in educational programs organized by Chiesi, MSD, Pfizer and Shionogi, received research support from MSD, Shionogi, and Venatorx Pharmaceuticals, and participated in evaluation of clinical trials for MSD and Pfizer. Y Doi has received honoraria for participation in scientific advisory boards for GSK, MSD, Gilead, Shionogi, MeijiSeika, Chugai, and bioMérieux, and received speaking fees from MSD, bioMérieux, and Shionogi. P J Simner has received research grants and consulting fees from OpGen Inc. and BD Diagnostics, research grants from Affinity Biosensors and Qiagen, and consulting fees from Shionogi Inc. and GeneCapture. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
Publisher Copyright:
© 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.
PY - 2022
Y1 - 2022
N2 - Introduction: Carbapenem-resistant (CR) Pseudomonas aeruginosa infections constitute a serious clinical threat globally. Patients are often critically ill and/or immunocompromised. Antibiotic options are limited and are currently centered on beta-lactam–beta-lactamase inhibitor (BL–BLI) combinations and the siderophore cephalosporin cefiderocol. Areas covered: This article reviews the mechanisms of P. aeruginosa resistance and their potential impact on the activity of current treatment options, along with evidence for the clinical efficacy of BL–BLI combinations in P. aeruginosa infections, some of which specifically target infections due to CR organisms. The preclinical and clinical evidence supporting cefiderocol as a treatment option for P. aeruginosa involving infections is also reviewed. Expert opinion: Cefiderocol is active against most known P. aeruginosa mechanisms mediating carbapenem resistance. It is stable against different serine- and metallo-beta-lactamases, and, due to its iron channel-dependent uptake mechanism, is not impacted by porin channel loss. Furthermore, the periplasmic level of cefiderocol is not affected by upregulated efflux pumps. The potential for on-treatment resistance development currently appears to be low, although more clinical data are required. Information from surveillance programs, real-world compassionate use, and clinical studies demonstrate that cefiderocol is an important treatment option for CR P. aeruginosa infections.
AB - Introduction: Carbapenem-resistant (CR) Pseudomonas aeruginosa infections constitute a serious clinical threat globally. Patients are often critically ill and/or immunocompromised. Antibiotic options are limited and are currently centered on beta-lactam–beta-lactamase inhibitor (BL–BLI) combinations and the siderophore cephalosporin cefiderocol. Areas covered: This article reviews the mechanisms of P. aeruginosa resistance and their potential impact on the activity of current treatment options, along with evidence for the clinical efficacy of BL–BLI combinations in P. aeruginosa infections, some of which specifically target infections due to CR organisms. The preclinical and clinical evidence supporting cefiderocol as a treatment option for P. aeruginosa involving infections is also reviewed. Expert opinion: Cefiderocol is active against most known P. aeruginosa mechanisms mediating carbapenem resistance. It is stable against different serine- and metallo-beta-lactamases, and, due to its iron channel-dependent uptake mechanism, is not impacted by porin channel loss. Furthermore, the periplasmic level of cefiderocol is not affected by upregulated efflux pumps. The potential for on-treatment resistance development currently appears to be low, although more clinical data are required. Information from surveillance programs, real-world compassionate use, and clinical studies demonstrate that cefiderocol is an important treatment option for CR P. aeruginosa infections.
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U2 - 10.1080/14787210.2022.2071701
DO - 10.1080/14787210.2022.2071701
M3 - Review article
C2 - 35502603
AN - SCOPUS:85130244453
VL - 20
SP - 1077
EP - 1094
JO - Expert Review of Anti-Infective Therapy
JF - Expert Review of Anti-Infective Therapy
SN - 1478-7210
IS - 8
ER -