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. 2024 Sep;13(9):1929-1948.
doi: 10.1007/s40121-024-01016-y. Epub 2024 Jul 12.

Use of Cefiderocol in Adult Patients: Descriptive Analysis from a Prospective, Multicenter, Cohort Study

Daniele Roberto Giacobbe  1   2 , Laura Labate  3 , Chiara Russo Artimagnella  3   4 , Cristina Marelli  4 , Alessio Signori  5 , Vincenzo Di Pilato  6 , Chiara Aldieri  7 , Alessandra Bandera  8   9 , Federica Briano  10 , Bruno Cacopardo  11 , Alessandra Calabresi  12 , Federico Capra Marzani  13 , Anna Carretta  14 , Annamaria Cattelan  15 , Luca Ceccarelli  16   17 , Giovanni Cenderello  18 , Silvia Corcione  19   20 , Andrea Cortegiani  21   22 , Rosario Cultrera  23   24 , Francesco Giuseppe De Rosa  19 , Valerio Del Bono  7 , Filippo Del Puente  25 , Chiara Fanelli  26 , Fiorenza Fava  27 , Daniela Francisci  28 , Nicholas Geremia  29   30 , Lucia Graziani  31 , Andrea Lombardi  8   9 , Angela Raffaella Losito  32 , Ivana Maida  26 , Andrea Marino  11 , Maria Mazzitelli  15 , Marco Merli  33 , Roberta Monardo  34   35 , Alessandra Mularoni  36 , Chiara Oltolini  33 , Carlo Pallotto  28 , Emanuele Pontali  25 , Francesca Raffaelli  32 , Matteo Rinaldi  16   17 , Marco Ripa  34   35 , Teresa Antonia Santantonio  14 , Francesco Saverio Serino  37 , Michele Spinicci  31   38 , Carlo Torti  32   39 , Enrico Maria Trecarichi  40   41 , Mario Tumbarello  42   43 , Malgorzata Mikulska  3   4 , Mauro Giacomini  44 , Anna Marchese  6   45 , Antonio Vena  3   4 , Matteo Bassetti  3   4 ; CEFI-SITA investigators
Collaborators, Affiliations

Use of Cefiderocol in Adult Patients: Descriptive Analysis from a Prospective, Multicenter, Cohort Study

Daniele Roberto Giacobbe et al. Infect Dis Ther. 2024 Sep.

Abstract

Introduction: Cefiderocol is a siderophore cephalosporin showing activity against various carbapenem-resistant Gram-negative bacteria (CR-GNB). No data currently exist about real-world use of cefiderocol in terms of types of therapy (e.g., empirical or targeted, monotherapy or combined regimens), indications, and patient characteristics.

Methods: In this multicenter, prospective study, we aimed at describing the use of cefiderocol in terms of types of therapy, indications, and patient characteristics.

Results: Cefiderocol was administered as empirical and targeted therapy in 27.5% (55/200) and 72.5% (145/200) of cases, respectively. Overall, it was administered as monotherapy in 101/200 cases (50.5%) and as part of a combined regimen for CR-GNB infections in the remaining 99/200 cases (49.5%). In multivariable analysis, previous isolation of carbapenem-resistant Acinetobacter baumannii odds ratio (OR) 2.56, with 95% confidence interval (95% CI) 1.01-6.46, p = 0.047] and previous hematopoietic stem cell transplantation (OR 8.73, 95% CI 1.05-72.54, p = 0.045) were associated with administration of cefiderocol as part of a combined regimen, whereas chronic kidney disease was associated with cefiderocol monotherapy (OR 0.38 for combined regimen, 95% CI 0.16-0.91, p = 0.029). Cumulative 30-day mortality was 19.8%, 45.0%, 20.7%, and 22.7% in patients receiving targeted cefiderocol for infections by Enterobacterales, A. baumannii, Pseudomonas aeruginosa, and any metallo-β-lactamase producers, respectively.

Conclusions: Cefiderocol is mainly used for targeted treatment, although empirical therapies account for more than 25% of prescriptions, thus requiring dedicated standardization and guidance. The almost equal distribution of cefiderocol monotherapy and cefiderocol-based combination therapies underlines the need for further study to ascertain possible differences in efficacy between the two approaches.

Keywords: Antimicrobial resistance; Carbapenem resistance; Carbapenemases; Cefiderocol; Clinical practice.

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Conflict of interest statement

Outside the submitted work, Daniele Roberto Giacobbe reports investigator-initiated grants from Pfizer, BioMérieux, and Gilead Italia, and speaker/advisory board fees from Pfizer, Menarini, and Tillotts Pharma. Outside the submitted work, Matteo Bassetti has received funding for scientific advisory boards, travel, and speaker honoraria from Angelini, Astellas, Bayer, bioMérieux, Cidara, Cipla, Gilead, Menarini, MSD, Pfizer, Shionogi, Tetraphase, and Nabriva. Outside the submitted work, Vincenzo di Pilato reports travel grants from Arrow Diagnostic, and speaker honoraria from A.D.A. Outside the submitted work, Emanuele Pontali has received funding for scientific advisory boards, travel, and/or speaker honoraria from Abbvie, Angelini, Gilead, Janssen, MSD, and Viiv. Outside the submitted work, Andrea Lombardi reports travel grants from Shionogi. Outside the submitted work, Rosario Cultrera has received funding for scientific advisory boards, travel, and speaker honoraria from Angelini, Menarini, MSD, Pfizer, Shionogi, and TRX Italy. Outside the submitted work, Andrea Cortegiani reports fees for lectures/ advisory board membership from Gilead, MSD, Mundipharma, Pfizer, Shionogi. The other authors have no conflicts of interests to disclose.

Figures

Fig. 1
Fig. 1
Cumulative mortality up to day 30 in patients receiving targeted cefiderocol therapy for Enterobacterales infection (panel A), Acinetobacter baumannii infection (panel B), Pseudomonas aeruginosa infection (panel C), and MBL-producing Gram-negative bacteria (panel D). MBL metallo-β-lactamases. Analyses limited to Infection by only one Gram negative genus (with the exception of Enterobacterales infection, for which concomitant infection by more than one member of the Enterobacterales order was also considered). The time of origin was set at the day of cefiderocol initiation. Death was the event of interest and right-censoring was applied at the end of follow-up (hospital discharge or day 30, whichever came first). Site/s of Enterobacterales infection: bloodstream infection (n = 12); lower respiratory tract infection (n = 7); urinary tract infection (n = 2); skin and soft tissue infection (n = 1); intra-abdominal infection (n = 1); intra-abdominal infection plus bloodstream infection (n = 1); lower respiratory tract infection plus bloodstream infection (n = 1); urinary tract infection plus bloodstream infection (n = 1). Site/s of P. aeruginosa infection (n = 25): lower respiratory tract infection (n = 12); bloodstream infection (n = 6); urinary tract infection (n = 2); bone and joint infection plus bloodstream infection (n = 1); intra-abdominal infection (n = 1); lower respiratory tract infection plus bloodstream infection (n = 1); skin and soft tissue infection (n = 1); skin and soft tissue infection plus bloodstream infection (n = 1). Site/s of A. baumannii infection (n = 67): lower respiratory tract infection (n = 30); bloodstream infection (n = 29); bone and joint infection (n = 2); urinary tract infection (n = 2); intra-abdominal infection (n = 1); lower respiratory tract infection plus bloodstream infection (n = 1); skin and soft tissue infection (n = 1); site/s not reported (n = 1). Site/s of MBL-producing Gram-negative infection (n = 22): lower respiratory tract infection (n = 8); bloodstream infection (n = 5); urinary tract infection (n = 3); intra-abdominal infection (n = 2); skin and soft tissue infection (n = 2): lower respiratory tract infection plus bloodstream infection (n = 1); skin and soft tissue infection plus bloodstream infection (n = 1). Type of MBL enzyme (n = 20): NDM (n = 12); VIM (n = 19); NDM (n = 3). Type of MBL-producing causative agent: P. aeruginosa (n = 12); Enterobacterales (n = 10)
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