Safety and efficacy of cefiderocol for off‐label treatment indications: A systematic review

Abstract

Purpose Cefiderocol is a siderophore cephalosporin recently approved by the United States Food and Drug Administration for the treatment of hospital‐ and ventilator‐acquired bacterial pneumonia and complicated urinary tract infections. However, there is potential for cefiderocol utility for a variety of other infections. The purpose of this systematic review was to identify literature examining the safety and efficacy of cefiderocol for off‐label indications. Methods The PRISMA guidelines were utilized for reporting. Databases searched included PubMed, Scopus, and Embase, from inception to September 2021. Manuscripts describing cefiderocol off‐label use in clinical settings were included. Exclusion criteria were studies focused on labeled indications, animal studies, pharmacodynamic/pharmacokinetic studies, in vitro or laboratory studies, and manuscripts in languages other than English or Arabic. Each stage of review utilized two independent investigators, with conflicts resolved and critical appraisal performed. Data regarding presentation, clinical course, and infection characteristics were extracted and descriptively analyzed. Results The search identified a total of 985 records, narrowed to a final set of 27 studies. Among studies included were 18 (66.7%) case reports, 8 (29.6%) case series, and 1 (3.7%) phase 3 clinical trial. Cefiderocol was most frequently used off‐label for bacteremia/sepsis with or without an identified source in 51 (67.1%) out of a total of 76 included patients. Among case series/reports with available data, 43 of 53 patients (81.1%) received combination antibiotic therapy. The most common pathogens identified included multi/extensively drug‐resistant Pseudomonas aeruginosa and/or Acinetobacter baumannii. Various clinical end points were reported, while microbiological end points were reported in 18 (66.7%) studies. Cefiderocol‐related side effects were uncommon and rarely use‐limiting. Conclusions This systematic review depicts relative clinical effectiveness of off‐label cefiderocol, most commonly for P. aeruginosa and A. baumannii infections as combination antibiotic therapy. Further study is needed to elucidate the safety and efficacy of cefiderocol across an expanded set of patients and indications.

Case series: Stenotrophomonas maltophilia in pediatric oncology patients

“…10 However, cefiderocol is only FDA indicated for patients 18 years and older. 11 A recent study reported a 5.9% MDR resistance to TMP/SMX, 14.3% resistance to levofloxacin, and 31% resistance to ceftazidime in S. maltophilia bloodstream isolates from pediatric patients. 12 Use of combination therapy has been suggested for treatment of moderate T A B L E 1 Directed antibiotics for the treatment of S. maltophilia.…”

“…Other choices for treatment include fluoroquinolones, ceftazidime, tetracyclines including tigecycline and minocycline (Table 1) while newer generation beta‐lactams like cefiderocol are reserved for MDR organisms 10 . However, cefiderocol is only FDA indicated for patients 18 years and older 11 . A recent study reported a 5.9% MDR resistance to TMP/SMX, 14.3% resistance to levofloxacin, and 31% resistance to ceftazidime in S. maltophilia bloodstream isolates from pediatric patients 12 .…”

Meropenem/Vaborbactam and Cefiderocol as Combination or Monotherapy to Treat Multi-Drug Resistant Gram-Negative Infections: A Regional Cross-Sectional Survey from Piedmont Infectious Disease Unit Network (PIDUN)

“…The debate about the most valuable option to use these new drugs, is still open, especially regarding the choice between monotherapy and combination therapy. Recommendations are not univocal for MDROs: clinical setting, pathogen isolation, infection source and disease’s severity assessment should guide the prescription [ 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 ].…”

Current and Potential Therapeutic Options for Infections Caused by Difficult-to-Treat and Pandrug Resistant Gram-Negative Bacteria in Critically Ill Patients

“…Fourteen-day all-cause mortality, clinical cure, and microbiologic eradication were similar between treatment groups for participants infected with A. baumannii ; however, this group only comprised 16% of the study population, of which 66% of isolates were carbapenemase-resistant [ 111 ]. Cefiderocol has also been administrated as compassionate use in a limited number of case series with infections caused by XDR and PDR A. baumannii pathogens, resulting in a clinical success of 80% (20/25) [ 67 , 98 ]. Overall, the necessity of further studies to elucidate the true role of cefiderocol against A. baumannii infections in real life patients is needed.…”