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Frequency of cefiderocol heteroresistance among patients treated with cefiderocol for carbapenem-resistant infections.
JAC Antimicrob Resist
October 2024
Department of Clinical and Experimental Medicine, Azienda Osperdaliero Universitaria Pisana, University of Pisa, Pisa, Italy.
Article Synopsis
- - The study investigates the role of heteroresistance in cefiderocol treatment failure among patients with carbapenem-resistant Acinetobacter baumannii (CRAb) infections, finding a significant portion (59%) of the isolates had heteroresistance, particularly higher in Italy compared to the USA.
- - Patients with cefiderocol-heteroresistant strains had worse clinical outcomes, with 81% experiencing treatment failure, compared to 55% for those with susceptible strains, and higher minimum inhibitory concentrations (MICs) were linked to increased failure rates.
- - Whole-genome sequencing revealed a genetic mutation in some heteroresistant isolates, supporting the idea that both higher MICs and the presence of resistant subpopulations contribute to
Cefiderocol heteroresistance associated with mutations in TonB-dependent receptor genes in of clinical origin.
Antimicrob Agents Chemother
August 2024
Division of Infectious Diseases, Houston Methodist Hospital, Houston, Texas, USA.
The siderophore-cephalosporin cefiderocol (FDC) presents a promising treatment option for carbapenem-resistant (CR) (PA). FDC circumvents traditional porin and efflux-mediated resistance by utilizing TonB-dependent receptors (TBDRs) to access the periplasmic space. Emerging FDC resistance has been associated with loss of function mutations within TBDR genes or the regulatory genes controlling TBDR expression.
View Article and Find Full Text PDFTreatment Strategies of Colistin Resistance Infections.
Antibiotics (Basel)
May 2024
Department of Internal Medicine & Infectious Diseases, University General Hospital of Heraklion, 71500 Heraklion, Greece.
Article Synopsis
- Colistin resistance is becoming a major issue in clinical practice, primarily due to genetic changes that affect how bacteria respond to the antibiotic, such as modifications to their cell structures and membrane permeability.
- The review discusses new treatment options being developed, including antibiotics like cefiderocol and sulbactam/durlobactam, as well as various drug combinations aimed at combating colistin-resistant infections.
- While many of the combinations focus on polymyxins, there’s growing interest in non-polymyxin alternatives, although further research is needed to establish effective treatment strategies.
The siderophore-cephalosporin cefiderocol(FDC) presents a promising treatment option for carbapenem-resistant (CR) (PA). FDC circumvents traditional porin and efflux mediated resistance by utilizing TonB-dependent receptors (TBDRs) to access the periplasmic space. Emerging FDC resistance has been associated with loss of function mutations within TBDR genes or the regulatory genes controlling TBDR expression.
View Article and Find Full Text PDFDynamic within-host cefiderocol heteroresistance caused by bla amplification in pandrug-resistant and hypervirulent Klebsiella pneumoniae sequence type 11.
Drug Resist Updat
March 2024
Department of Infectious Disease, Peking University Third Hospital, Beijing, China; Center of Infectious Disease, Peking University Third Hospital, Beijing, China; Institute of Medical Technology, Peking University Health Science Center, Beijing, China; Department of Pulmonary and Critical Care Medicine, Peking University Third Hospital, Beijing, China. Electronic address:
Aims: Although cefiderocol (FDC) is not prescribed in China, FDC-resistant pandrug-resistant hypervirulent Klebsiella pneumoniae (PDR-hvKp) is emerging. In this study, we performed FDC susceptibility testing of clinical Kp isolates to explore the prevalence of FDC-resistant isolates and the mechanism of FDC-resistance.
Methods: We retrospectively selected 151 carbapenem-resistant Kp isolates to assess FDC susceptibility.
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