Iron serum levels and iron homeostasis parameters in patients with nosocomial pneumonia treated with cefiderocol: post hoc analysis of the APEKS-NP study

Eric P Skaar, Roger Echols, Yuko Matsunaga, Anju Menon, Simon Portsmouth, Eric P Skaar, Roger Echols, Yuko Matsunaga, Anju Menon, Simon Portsmouth

Abstract

Critically ill patients often present with low serum iron levels or anemia. We evaluated the impact of iron levels and iron homeostasis on the efficacy and safety of cefiderocol, an iron-chelator siderophore cephalosporin, in patients with nosocomial pneumonia in a post hoc analysis of the randomized, double-blind, Phase 3 APEKS-NP study (NCT03032380). Patients with Gram-negative nosocomial pneumonia received cefiderocol 2 g, 3-h infusion, q8h, or high-dose, extended-infusion meropenem 2 g, 3-h infusion, q8h, for 7-14 days. Efficacy and safety parameters, including specific iron homeostasis parameters (i.e., hepcidin, iron, total iron binding capacity, transferrin saturation), were analyzed according to baseline iron levels. In the cefiderocol and meropenem arms, 79.1% (117/148) and 83.3% (125/150) randomized patients, respectively, had low baseline serum iron levels. Rates of 14-day (12.3% [14/114] vs 11.6% [14/121]) and 28-day all-cause mortality (20.5% [23/112] vs 19.0% [23/121]), clinical cure (63.2% [72/114] vs 67.2% [82/122]), and microbiological eradication (43.6% [41/94] vs 48.1% [51/106]) at test of cure were similar in cefiderocol vs meropenem arms, respectively. In the overall safety population, rates of anemia-related adverse events were similar (cefiderocol arm 18.2% [27/148], meropenem arm 18.7% [28/150]). Changes from baseline to test of cure in hepcidin, iron, total iron binding capacity, and transferrin saturation were similar between treatment arms. Cefiderocol treatment did not affect iron homeostasis, and its efficacy and safety were not influenced by baseline serum iron levels. Clinicaltrials.gov registration: NCT03032380. Date of registration: 26 January 2017.

Keywords: Cefiderocol; Critically ill; Iron homeostasis; Nosocomial pneumonia; Safety.

Conflict of interest statement

YM, AM, and SP are employees of Shionogi Inc. EPS and RE are consultants for Shionogi and received consultancy fee.

© 2022. The Author(s).

Figures

Fig. 1
Fig. 1
Changes in serum hemoglobin between baseline and test of cure in the overall safety population
Fig. 2
Fig. 2
Changes in serum iron, hepcidin, transferrin saturation, and total iron binding capacity between baseline and test of cure in the overall safety population

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