English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Background Cefiderocol (CFDC), the first siderophore cephalosporin, is approved in the United States (complicated urinary tract infections [cUTI]) and Europe for the treatment of patients with Gram-negative (GN) infections with limited treatment options. Methods This analysis investigated the safety profile of CFDC across three prospective, multicenter, randomized clinical studies: APEKS-cUTI (double-blind, non-inferiority Phase 2 study in patients with cUTI) vs imipenem-cilastatin (1 g/1 g, three-times daily); APEKS-NP (double-blind, non-inferiority Phase 3 study in patients with nosocomial pneumonia [NP]) vs meropenem (2 g, q8h); CREDIBLE-CR (open-label, descriptive Phase 3 study in patients with cUTI, NP, bloodstream infections/sepsis [BSI/sepsis]) caused by carbapenem-resistant GN bacteria; patients in the control arm received best available therapy (BAT; up to 3 agents, dosing based on local label). CFDC was given at 2 g, q8h, infused over 1 (APEKS-cUTI) or 3 (APEKS-NP, CREDIBLE-CR) hours. One adjunctive agent with CFDC was only allowed in CREDIBLE-CR. Results 549 patients were treated with CFDC, 347 control treated (Table 1). More than 50% of patients were aged ≥65 years, except BAT arm in CREDIBLE-CR. The majority of patients were admitted to the ICU in APEKS-NP and CREDIBLE-CR. The median treatment duration with CFDC was similar (9–11 days) across studies. The rates of TEAEs and serious AEs (SAEs) between CDFC and comparators were similar in each study (Table 2). The rates of adverse drug reactions were lower with CFDC than with comparators in each study, with a greater difference in CREDIBLE-CR than in APEKS-cUTI and APEKS-NP. TEAEs leading to death rates are shown in Table 2. Eight CFDC-related Clostridioides difficile infections occurred across studies (APEKS-cUTI: n=1; APEKS-NP: n=4; CREDIBLE-CR: n=3 [ie, C. difficile colitis; pseudomembranous colitis]). In total, eight experienced seizures (APEKS-cUTI: CFDC n=1; APEKS-NP: CFDC n=3, meropenem n=2; CREDIBLE-CR: CFDC n=1, BAT n=1), none of which were related to study drugs. Parameters of iron homeostasis showed no differences between CFDC and comparators. Table 1. Baseline characteristics and treatment duration (safety populations) Table 2. Overall safety parameters (safety populations) Conclusion CFDC demonstrated a comparable safety profile to carbapenems or other cephalosporins and was generally well tolerated in critically ill patients. Disclosures Yuko Matsunaga, MD, Shionogi Inc. (Employee) Takuhiro Sonoyama, MD, Shionogi &amp; Co., Ltd. (Employee) Luis Casanova, PharmD, Shionogi B.V. (Employee) Tsutae Den Nagata, MD, Shionogi &amp; Co., Ltd. (Employee) Roger Echols, MD, Shionogi Inc. (Consultant) Fabio De Gregorio, MD, Shionogi B.V. (Employee) Eriko Ogura, MD, Shionogi &amp; Co., Ltd. (Employee) Simon Portsmouth, MD, Shionogi Inc. (Employee)

open forum infectious diseases

1292. Safety Profile of the Novel Siderophore Cephalosporin Cefiderocol in Randomized Phase 2 and Phase 3 Clinical Studies of Serious Gram-Negative Infections