Cefiderocol in the treatment of systemic carbapenemase-producing multidrug-resistant Klebsiella pneumoniae infection

Lampejo, Temi; Cherian, Benny P; Tan, Mei Gie Meiqi; Wareham, David W.

doi:10.1016/j.jgar.2020.10.008

Cited by 6 publications

(20 citation statements)

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“…We identified 30 case reports and case series including 78 patients who had recalcitrant infections caused by MDR Gram-negative bacteria, and treated with salvage treatment or compassionate use of cefiderocol in real-world settings ( Edgeworth et al, 2019 ; Stevens and Clancy, 2019 ; Trecarichi et al, 2019 ; Alamarat et al, 2020 ; Contreras et al, 2020 ; Dagher et al, 2020 ; Kufel et al, 2020 ; Lampejo et al, 2020 ; Oliva et al, 2020 ; Siméon et al, 2020 ; Zingg et al, 2020 ; Bavaro et al, 2021a ; Bavaro et al, 2021b ; Bleibtreu et al, 2021 ; Bodro et al, 2021 ; Borghesi et al, 2021 ; Carney et al, 2021 ; Chavda et al, 2021 ; Cipko et al, 2021 ; Falcone et al, 2021 ; Fratoni et al, 2021 ; Grande Perez et al, 2021 ; Grasa et al, 2021 ; Klein et al, 2021 ; König et al, 2021 ; Mabayoje et al, 2021 ; Martinez et al, 2021 ; Mc Gann et al, 2021 ; Warner et al, 2021 ; Zaidan et al, 2021 ). The detailed characteristics of these cases are summarized in Supplementary Table S3 .…”

Section: Resultsmentioning

confidence: 99%

Cefiderocol for the Treatment of Multidrug-Resistant Gram-Negative Bacteria: A Systematic Review of Currently Available Evidence

et al. 2022

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Cefiderocol is a novel synthetic siderophore-conjugated antibiotic that hijacks the bacterial iron transport systems facilitating drug entry into cells, achieving high periplasmic concentrations. This systematic review analyzed the currently available literature on cefiderocol. It summarized in vitro susceptibility data, in vivo antimicrobial activity, pharmacokinetics/pharmacodynamics (PK/PD), clinical efficacy, safety and resistance mechanisms of cefiderocol. Cefiderocol has potent in vitro and in vivo activity against multidrug-resistant (MDR) Gram-negative bacteria, including carbapenem-resistant isolates. But New Delhi Metallo-β-lactamase (NDM)- positive isolates showed significantly higher MICs than other carbapenemase-producing Enterobacterales, with a susceptible rate of 83.4% for cefiderocol. Cefiderocol is well-tolerated, and the PK/PD target values can be achieved using a standard dose regimen or adjusted doses according to renal function. Clinical trials demonstrated that cefiderocol was non-inferiority to the comparator drugs in treating complicated urinary tract infection and nosocomial pneumonia. Case reports and series showed that cefiderocol was a promising therapeutic agent in carbapenem-resistant infections. However, resistant isolates and reduced susceptibility during treatment to cefiderocol have already been reported. In conclusion, cefiderocol is a promising powerful weapon for treating MDR recalcitrant infections.

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Section: Resultsmentioning

confidence: 99%

Cefiderocol for the Treatment of Multidrug-Resistant Gram-Negative Bacteria: A Systematic Review of Currently Available Evidence

et al. 2022

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“…Cefiderocol is a siderophore cephalosporin with unique ability to enter the bacterial periplasmic space that has enhanced stability against -lactamases including ESBLs and CPases; its activity appears equal to or superior to CAZ-AVI against CPase-producing Enterobacteriaceae 224 . Cefiderocol has potent activity against GNB including MDR Enterobacteriaceae and non-fermenters [225][226][227]…”

Section: Cefiderocol (A Novel Siderophore Cephalosporin)mentioning

confidence: 99%

Escalating antimicrobial resistance among Enterobacteriaceae: focus on carbapenemases

Lynch¹,

Clark

Zhanel

2021

Expert Opinion on Pharmacotherapy

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aminoglycosides (AG); antimicrobial resistance (AMR); -lactamase inhibitors (BLI); blood stream infections (BSIs) ; carbapenem (CP); carbapenemase (CPase); carbapenem-resistant (CR); carbapenemresistant Enterobacterales (CRE) ;-lactam inhibitor (BLI); CP-resistant K. pneumoniae (CRKP); CPsusceptible K. pneumoniae (CSKP); ceftazidime/avibactam (CAZ-AVI); cephalosporins (CEPHS); central line-associated (CLA); central venous catheter (CVC); community-acquired infection (CAI); complicated intra-abdominal infection (c-IAI); complicated urinary tract infection (c-UTI); defined daily dose (DDD) ; extended-spectrum -lactamases (ESBLs); extensively Drug Resistant (eXDR); fluoroquinolones (FQ); Gram negative bacteria (GNB); gross domestic product per capita (GDPPC); high-income countries (HICs); hospital acquired infection (HAI); imipenem-relebactam (IMI-REL); intensive care units (ICUs); Klebsiella pneumoniae carbapenemases (KPCs); long-term care facilities (LTCFs); low-and middleincome countries (LMICs); mechanical ventilation; metallo-lactamase (MBL); minimal inhibitory concentration (MIC); mobile genetic elements (MGEs); multidrug resistant (MDR); New Delhi Metalloproteinase-1 (NDM-1); non-Proteus Enterobacterales (NPE); organ transplant recipients (OTR); piperacillin/tazobactam (PTZ); solid organ transplant (SOT); tigecycline (TGC); ventilator-associated pneumonia (VAP)

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“…Among the 27 studies were 18 (66.7%) case reports, [19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36] eight (29.6%) case series, [11][12][13][14][15][16][17][18] and one (3.7%) phase 3 clinical trial Table 1. 10 Across the studies, 76 patients were included.…”

Section: Summary Of Included Studiesmentioning

confidence: 99%

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

et al. 2022

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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.

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Cefiderocol in the treatment of systemic carbapenemase-producing multidrug-resistant Klebsiella pneumoniae infection

Cited by 6 publications

References 3 publications

Cefiderocol for the Treatment of Multidrug-Resistant Gram-Negative Bacteria: A Systematic Review of Currently Available Evidence

Cefiderocol for the Treatment of Multidrug-Resistant Gram-Negative Bacteria: A Systematic Review of Currently Available Evidence

Escalating antimicrobial resistance among Enterobacteriaceae: focus on carbapenemases

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

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