Abstract
Cefiderocol is a new siderophore cephalosporin approved for the treatment of multidrug resistant bacteria including activity against carbapenem-resistant Enterobacterales and Pseudomonas aeruginosa. As cephalosporins are known for their high pharmacokinetic variability in critically ill patients, cefiderocol therapeutic drug monitoring might become a valuable tool. Therefore, we aimed to develop and validate a simple, rapid, cost-effective high performance liquid chromatography (HPLC) method for the quantification of cefiderocol in serum. Samples were treated for protein precipitation followed by chromatographic separation on a reverse phase column (HPLC C-18) with gradient elution of the mobile phase. Cefiderocol was detected via UV absorption and quantification was performed with the internal standard (metronidazole) method. The calibration range showed linearity from 4 to 160 mg/L. The intra and interday precision was less than 10% with a recovery rate of 81%. The method was successfully used for the analysis of subsequent serum samples of critically ill patients and showed good performance in monitoring serum levels and optimizing antibiotic therapy.
Highlights
Cefiderocol is a novel siderophore cephalosporin used for the treatment of nosocomial infections such as hospital acquired and ventilator associated pneumonia (HAP/VAP), complicated urinary tract infections and difficult to treat Gram-negative bacteria in adults
Sufficient peak separation from other beta-lactam antibiotics quantifyable with this method was achieved with the given high performance liquid chromatography (HPLC)-UV parameters
Stability of extracted samples in the auto sampler at 10 ◦ C during processing time was checked for a day shift of a maximum of 24 h. With this HPLC-UV method, cefiderocol therapeutic drug monitoring can be performed on a daily basis with a quick turn-around-time based on a cost-effective analytical method, which can be implemented in smaller laboratories or hospital pharmacies
Summary
Cefiderocol is a novel siderophore cephalosporin used for the treatment of nosocomial infections such as hospital acquired and ventilator associated pneumonia (HAP/VAP), complicated urinary tract infections (cUTIs) and difficult to treat Gram-negative bacteria in adults. It is closely related to both ceftazidime and cefepime. By adding a siderophore-like sidechain to the structure, drug concentration remains very high at the side of action (“Trojan horse strategy”). Its outstanding bactericidal Gram-negative spectrum shows activity against strains producing metallo-ß-lactamases and shows minimal inhibitory concentrations (MICs) of < 4 mg/L in most of the tested isolates [1]. Susceptible isolates include carbapenem resistant strains such as extended spectrum betalactamaseor carbapenemase producing Enterobacterales, Pseudomonas aeruginosa and Acinetobacter baumannii and other multidrug resistant (MDR) Gram-negative pathogens [1]
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