Evaluating Cefiderocol in the Treatment of Multidrug-Resistant Gram-Negative Bacilli: A Review of the Emerging Data

Daniele Roberto Giacobbe^{1

2}, Eugenio Ciacco³, Corrado Girmenia⁴, Federico Pea^{5

6}, Gian Maria Rossolini^{7

8}, Giovanni Sotgiu⁹, Carlo Tascini¹⁰, Mario Tumbarello^{11

12}, Pierluigi Viale^{5

6}, Matteo Bassetti^{1

2}; ISGRI-SITA (Italian Study Group on Resistant Infections of the Italian Society of Anti-infective Therapy)

Affiliations

¹ Clinica Malattie Infettive, Ospedale Policlinico San Martino - IRCCS, Genoa, Italy.
² Department of Health Sciences, University of Genoa, Genoa, Italy.
³ Pharmacy Unit, S. Salvatore Hospital, ASL1 Abruzzo, L'Aquila, Italy.
⁴ Hematology, Dipartimento Medicina Traslazionale e di Precisione, AOU Policlinico Umberto I, Sapienza University of Rome, Rome, Italy.
⁵ Department of Medical and Surgical Sciences, Alma Mater Studiorum, University of Bologna, Bologna, Italy.
⁶ University Hospital IRCCS Policlinico Sant'Orsola Bologna, Bologna, Italy.
⁷ Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.
⁸ Clinical Microbiology and Virology Unit, Florence Careggi University Hospital, Florence, Italy.
⁹ Department of Medical, Surgical and Experimental Sciences, University of Sassari, Sassari, Italy.
¹⁰ SOC Malattie Infettive, Azienda Sanitaria Integrata, University of Udine, Udine, Italy.
¹¹ Dipartimento di Scienze di Laboratorio e Infettivologiche, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.
¹² Dipartimento di Sicurezza e Bioetica, Università Cattolica del Sacro Cuore, Rome, Italy.

PMID: 33402840
PMCID: PMC7778378
DOI: 10.2147/IDR.S205309

Review

Evaluating Cefiderocol in the Treatment of Multidrug-Resistant Gram-Negative Bacilli: A Review of the Emerging Data

Daniele Roberto Giacobbe et al. Infect Drug Resist. 2020.

. 2020 Dec 29:13:4697-4711.

doi: 10.2147/IDR.S205309. eCollection 2020.

Authors

Affiliations

¹ Clinica Malattie Infettive, Ospedale Policlinico San Martino - IRCCS, Genoa, Italy.
² Department of Health Sciences, University of Genoa, Genoa, Italy.
³ Pharmacy Unit, S. Salvatore Hospital, ASL1 Abruzzo, L'Aquila, Italy.
⁴ Hematology, Dipartimento Medicina Traslazionale e di Precisione, AOU Policlinico Umberto I, Sapienza University of Rome, Rome, Italy.
⁵ Department of Medical and Surgical Sciences, Alma Mater Studiorum, University of Bologna, Bologna, Italy.
⁶ University Hospital IRCCS Policlinico Sant'Orsola Bologna, Bologna, Italy.
⁷ Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.
⁸ Clinical Microbiology and Virology Unit, Florence Careggi University Hospital, Florence, Italy.
⁹ Department of Medical, Surgical and Experimental Sciences, University of Sassari, Sassari, Italy.
¹⁰ SOC Malattie Infettive, Azienda Sanitaria Integrata, University of Udine, Udine, Italy.
¹¹ Dipartimento di Scienze di Laboratorio e Infettivologiche, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.
¹² Dipartimento di Sicurezza e Bioetica, Università Cattolica del Sacro Cuore, Rome, Italy.

PMID: 33402840
PMCID: PMC7778378
DOI: 10.2147/IDR.S205309

Abstract

Infections due to multidrug-resistant Gram-negative bacteria (MDR-GNB), especially when carbapenem resistant, have been very difficult to manage in the last fifteen years, owing to the paucity of dependable therapeutic options. Cefiderocol is a siderophore cephalosporin recently approved by the Food and Drug Administration (FDA) and European Medicines Agency (EMA) that may have the potential to fill some of the remaining gaps in the treatment of MDR-GNB infections. Among others, cefiderocol demonstrated in vitro activity against carbapenem-resistant Acinetobacter baumannii and metallo-β-lactamases producers. Clinical data from both registrative studies and post-marketing experiences are essential to confirm whether these promises from in vitro studies could readily translate into clinical practice, as well as to delineate the precise place in therapy for cefiderocol for the treatment of MDR-GNB in the near future. Because of its unique potential, it is essential to provide both randomized controlled trials (RCT) and real-life data to improve the ability of clinicians to exploit its benefit in both empirical and targeted treatment of MDR-GNB infections. In this narrative review, we discuss the emerging data from pivotal RCT and initial real-life experiences on the use of cefiderocol for the treatment of MDR-GNB infections.

Keywords: Acinetobacter; Enterobacterales; Pseudomonas; antimicrobial resistance; cefiderocol; siderophore.

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Conflict of interest statement

Outside the submitted work, DRG reports honoraria from Stepstone Pharma GmbH and unconditional grants from MSD Italia and Correvio Italia. FP reports grants from Shionogi, during the conduct of the study; personal fees from Angelini, Basilea Pharmaceutica, Gilead, Hikma, Merck Sharp & Dohme, Nordic Pharma, Novartis, Shionogi, Thermo Fisher, and Sandoz, outside the submitted work. Outside the submitted work, he has participated in advisory boards and/or received speaker honoraria from Angelini, Basilea Pharmaceutica, Correvio, Gilead, Hikma, Merck Sharp & Dohme, Novartis, Sanofi Aventis, and Thermo-Fisher. GMR reports grants, personal fees from Shionogi, during the conduct of the study; grants, personal fees, non-financial support from Accelerate and Menarini; grants from Angelini, bioMérieux, Cepheid, Elitech, Merck, Nordic Pharma, Seegene, Zambon, Symcel, DID, Hain Lifescience GmbH, GenePoc, Setlance, Biomedical Service, Qvella, and Qlinea, outside the submitted work; personal fees from Becton Dickinson, Angelini, bioMérieux, Cepheid, Merck, Nordic Pharma, Pfizer, Venatorx, Zambon, Roche, Thermo Fisher, Beckman Coulter, Qpex, and Qiagen, outside the submitted work. CT reports personal fees from Correvio, Basilea, Hikma, MSD, Pfizer, Thermo Fisher, Zambon, Biomerieux, and Shionogi, and personal fees from Angelini, outside the submitted work. Outside the submitted work, he has received research grants, and/or been a consultant and/or received a fee for speaking from bioMérieux, Zambon, Basilea, Merck, Nordic Pharma, Angelini, Thermo Fisher, Biotest, Pfizer, Astra Zeneca, Shionogi, Hikma, Avir Pharma, Biotest. MT reports personal honoraria for participating in advisory boards and/or for meeting presentations from Angelini, Astellas, Menarini, MSD, Nordic Pharma, Pfizer, Roche, Shionogi, outside the submitted work. MB reports grants and personal fees from Shionogi, outside the submitted work. Outside the submitted work, he has participated in advisory boards and/or received speaker honoraria from Achaogen, Angelini, Astellas, Bayer, Basilea, BioMérieux, Cidara, Gilead, Menarini, MSD, Nabriva, Paratek, Pfizer, Roche, Melinta, Shionogi, Tetraphase, VenatoRx and Vifor and has received study grants from Angelini, Basilea, Astellas, Shionogi, Cidara, Melinta, Gilead, Pfizer and MSD.

References

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Evaluating Cefiderocol in the Treatment of Multidrug-Resistant Gram-Negative Bacilli: A Review of the Emerging Data

Affiliations

Evaluating Cefiderocol in the Treatment of Multidrug-Resistant Gram-Negative Bacilli: A Review of the Emerging Data

Authors

Affiliations

Abstract

Conflict of interest statement

References

Publication types

LinkOut - more resources

Full Text Sources

Research Materials