Comment on 'Cefiderocol, a New Siderophore Cephalosporin for the Treatment of Complicated Urinary Tract Infections Caused by Multidrug-resistant Pathogens: Preclinical and Clinical Pharmacokinetics, Pharmacodynamics, Efficacy and Safety'.

Dear Editors,

We read with interest the paper by Lee et al., which reviewed the in vitro, in vivo, and clinical data on cefiderocol [1]. However, we would like to address and highlight for your readers, the inaccurate characterization of all-cause mortality (ACM) in the APEKS-NP (NCT03032380, EudraCT 2016-003020-23) clinical trial and the subsequent conclusion drawn from this mischaracterization.

APEKS-NP was specifically designed to assess mortality in the nosocomial pneumonia patient population. Furthermore, APEKS-NP met its primary endpoint of non-inferiority. ACM in the cefiderocol arm was 12.4% versus 11.6% in the high-dose meropenem arm with a treatment difference of 0.8% [95% CI − 6.6 to 8.2] demonstrating that cefiderocol was non-inferior to high-dose meropenem in critically ill patients with nosocomial pneumonia caused by a broad range of Gram-negative bacteria, including Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacteriaceae [2, 3]. APEKS-NP subsequently served as the basis of approval by the US Food and Drug Administration (FDA) for use of cefiderocol in hospital-acquired and ventilator-acquired pneumonias (HAP/VAP) due to susceptible Gram-negative microorganisms, and supported removal of the restriction of limited or no alternative treatment options, and limited safety and efficacy data statements from the cefiderocol label [4].

From these results, Lee et al. draw the conclusion that cefiderocol should be limited only to the treatment of cUTIs from Gram-negative bacteria [1]. Our organization, as well as the FDA and European Medicines Agency, examined these results and concluded that cefiderocol can be used in patients with cUTI and HAP/VAP as evidenced by cefiderocol’s current FDA-approved indication as well as the pathogen-focused indication in the European Union [4, 5].

Thank you for the opportunity to respond to Lee et al. We hope this letter helps clarify the design, results and interpretation of APEKS-NP and cefiderocol’s place in therapy.