Abstract
Cefiderocol is a new cephalosporin displaying against extensively resistant (XDR) Gram-negative bacteria. We report our experience with cefiderocol-based combination therapies as “rescue” treatments in immunocompromised or critically ill patients or in patients with post-surgical infections who had failed previous regimens. A total of 13 patients were treated from 1 September 2020 to 31 March 2021. In total, 5/13 (38%) patients were classified as critically ill, due to severe COVID-19 lung failure; 4/13 (31%) patients had post-surgical infections and 4/13 (31%) had severe infections in immunocompromised subjects due to solid organ transplantation (2/4) or hematological malignancy (2/4). Overall, 10/13 infections were caused by carbapenem-resistant Acinetobacter baumannii, one by KPC-positive ceftazidime/avibactam-resistant Klebsiella pneumonia and two by Pseudomonas aeruginosa XDR. Based on clinical, microbiological and hematobiochemical evaluation, cefiderocol was associated with different companion drugs, particularly with fosfomycin, high-dose tigecycline and/or colistin. Microbiological eradication was achieved in all cases and the 30-day survival rate was 10/13; two patients died due to SARS-CoV-2 lung failure, whereas one death was attributed to subsequent infections. No recurrent infections within 30 days were reported. Finally, we hereby discuss the therapeutic potential of cefiderocol and the possible place in the therapy of this novel drug.
Highlights
Cefiderocol is a new generation siderophore cephalosporin which inhibits bacterial wall synthesis, utilizing a “Trojan horse” mechanism based on iron active transporters
It has been developed to be active against extensively resistant (XDR) Gram-negative bacteria (GNB), including carbapenemase-producing Enterobacterales (CPE) and non-fermentative GNB [1]
These pathogens are often involved in difficultto-treat (DTT) healthcare-associated infections (HCAI) [2], such as ventilator-associated pneumonia (VAP), [3] bloodstream infections (BSIs) [4] and intra-abdominal infections (IAIs) [5], and are burdened by elevated rates of morbidity and mortality, mostly in critically ill patients and immunocompromised hosts [6]
Summary
Cefiderocol (formerly S-649266) is a new generation siderophore cephalosporin which inhibits bacterial wall synthesis, utilizing a “Trojan horse” mechanism based on iron active transporters. It has been developed to be active against extensively resistant (XDR) Gram-negative bacteria (GNB), including carbapenemase-producing Enterobacterales (CPE) and non-fermentative GNB [1] These pathogens are often involved in difficultto-treat (DTT) healthcare-associated infections (HCAI) [2], such as ventilator-associated pneumonia (VAP), [3] bloodstream infections (BSIs) [4] and intra-abdominal infections (IAIs) [5], and are burdened by elevated rates of morbidity and mortality, mostly in critically ill patients and immunocompromised hosts [6]. Colistin resistance significantly increased in recent years, causing a further reduction of possible treatment options for XDR GNB infections [10] In this scenario, cefiderocol represents a novel and very promising therapeutic opportunity
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