Cefiderocol is a novel siderophore cephalosporin that forms a complex with extracellular free ferric iron, which leads to transportation across the outer cell membrane to exert its bactericidal activity through cell wall synthesis inhibition. This pharmacological property has rendered cefiderocol active against several clinically relevant MDR Gram-negative bacteria as evidenced by several in vitro and in vivo studies. Cefiderocol was first approved by the US FDA on 14 November 2019 for the treatment of complicated urinary tract infections. On 28 September 2020, cefiderocol was approved for the treatment of hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia. The FDA-approved indications are based on clinical data from the APEKS-cUTI, APEKS-NP and CREDIBLE-CR trials. In APEKS-cUTI, cefiderocol demonstrated non-inferiority to imipenem/cilastatin for the treatment of complicated urinary tract infection caused by MDR Gram-negative bacteria. In APEKS-NP, cefiderocol demonstrated non-inferiority to meropenem for treatment of nosocomial pneumonia. However, in CREDIBLE-CR, higher all-cause mortality was observed with cefiderocol compared with best available therapy for the treatment of severe infections caused by Gram-negative bacteria, primarily in the subset of patients with Acinetobacter spp. infections. Several case reports/series have demonstrated clinical success with cefiderocol for a variety of severe infections. The purpose of this article is to review available data on the mechanism of action, in vitro and in vivo data, pharmacokinetics, pharmacodynamics, susceptibility testing, efficacy and safety of cefiderocol to address its role in therapy.
Background: Approximately 30% of antimicrobials prescribed in the outpatient setting are unnecessary and up to 50% are inappropriate. Despite this, antimicrobial stewardship (AS) efforts mostly focus on the inpatient setting, and limited data describe AS interventions at hospital discharge. Acknowledging the potential value of discharge AS, we used our existing resources to review discharge oral antimicrobial prescriptions. Objective: The primary objective of this retrospective, single-center study was to evaluate the impact of an AS program on discharge oral antimicrobial prescriptions. Methods Discharge oral antimicrobial prescriptions sent to our hospital-operated outpatient pharmacy, reviewed by an infectious diseases (ID) pharmacist, and recorded into our data collection tool from September 1, 2020, to February 28, 2021, were evaluated retrospectively. The primary outcome was to identify the frequency a drug-related problem (DRP) was identified by an ID pharmacist. Secondary outcomes included DRP characterization, percentage of prescriptions with interventions, intervention acceptance rate, and reduction in antimicrobial days dispensed at discharge when interventions to limit treatment duration were accepted. Results: Of the 803 discharge oral antimicrobial prescriptions reviewed, at least 1 DRP was identified in 43.1% (346/803). The most frequently identified DRPs pertained to treatment duration, drug selection, and dose selection. At least 1 intervention was recommended in 42.8% (344/803) of prescriptions. In total, 438 interventions were made and the acceptance rate was 75.6% (331/438). The most common types of interventions included recommendations for a different duration, a different dose or frequency, and antimicrobial discontinuation. When interventions to reduce treatment duration were accepted, the median (interquartile range) number of antimicrobial days decreased from 8 (5-10) days to 4 (0-5.5) days ( P < 0.001). Conclusion and Relevance: An ID pharmacist’s review of discharge oral antimicrobial prescriptions sent to our hospital-operated outpatient pharmacy resulted in identification of DRPs and subsequent interventions in a substantial number of prescriptions.
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