Compassionate use of cefiderocol for carbapenem-resistant <i>Acinetobacter baumannii</i> prosthetic joint infection

Mabayoje, Diana Ayoola; NicFhogartaigh, Caoimhe; Cherian, Benny P; Tan, Mei Gie Meiqi; Wareham, David W.

doi:10.1093/jacamr/dlab055

Cited by 16 publications

(25 citation statements)

References 19 publications

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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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“…This group underwent microbiological failure in 80% of the cases [ 76 ]. The few reports available in the literature concerning the treatment of MDRO prosthetic joint infections with CFDC obtained encouraging clinical and microbiologic outcomes possibly linked to the peculiar activity of this agent in the biofilm [ 77 , 78 ].…”

Section: Resultsmentioning

confidence: 99%

Place in Therapy of the Newly Available Armamentarium for Multi-Drug-Resistant Gram-Negative Pathogens: Proposal of a Prescription Algorithm

et al. 2021

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The worldwide propagation of antimicrobial resistance represents one of the biggest threats to global health and development. Multi-drug-resistant organisms (MDROs), including carbapenem-resistant non-fermenting Gram-negatives and Enterobacterales, present a heterogeneous and mutating spread. Infections by MDRO are often associated with an unfavorable outcome, especially among critically ill populations. The polymyxins represented the backbone of antibiotic regimens for Gram-negative MDROs in recent decades, but their use presents multiple pitfalls. Luckily, new agents with potent activity against MDROs have become available in recent times and more are yet to come. Now, we have the duty to make the best use of these new therapeutic tools in order not to prematurely compromise their effectiveness and at the same time improve patients’ outcomes. We reviewed the current literature on ceftazidime/avibactam, meropenem/vaborbactam and cefiderocol, focusing on antimicrobial spectrum, on the prevalence and mechanisms of resistance development and on the main in vitro and clinical experiences available so far. Subsequently, we performed a step-by-step construction of a speculative algorithm for a reasoned prescription of these new antibiotics, contemplating both empirical and targeted use. Attention was specifically posed on patients with life-risk conditions and in settings with elevated prevalence of MDRO.

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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%

“…Bacteremia/sepsis was reported in 51 (67.1%) patients, 10,11,[13][14][15][16][17]24,29,30,32,36 most commonly with an unidentified infection (n = 10, 19.6%), 10,11,14,15 intra-abdominal infection (n = 8, 15.7%), 10,13,24,30 or intravenous line/catheter-associated source (n = 8, 15.7%). 10,11 The second and third most common infections were bone and joint infections (BJI) (n = 13, 17.1%) 12,16,[18][19][20][21][22][23]25,33,34 and CF exacerbations (n = 9, 11.8%). 17,27 Among the 76 patients, A. baumannii was identified in 32 (42.1%) patients, [10][11][12]14,16,18,23,25,33 P. aeruginosa was identified in 18 (23.7%) patients, [10][11][12][13]…”

Section: Summary Of Included Studiesmentioning

confidence: 99%

“…10,11 The second and third most common infections were bone and joint infections (BJI) (n = 13, 17.1%) 12,16,[18][19][20][21][22][23]25,33,34 and CF exacerbations (n = 9, 11.8%). 17,27 Among the 76 patients, A. baumannii was identified in 32 (42.1%) patients, [10][11][12]14,16,18,23,25,33 P. aeruginosa was identified in 18 (23.7%) patients, [10][11][12][13]15,16,[18][19][20]22,23,26,28,29,31,35,36 K. pneumoniae was identified in 17 (22.4%) patients, 10,11,16,19,24,28,30,32 and Achromobacter spp was identified in eight (10.5%) patients.…”

Section: Summary Of Included Studiesmentioning

confidence: 99%

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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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Compassionate use of cefiderocol for carbapenem-resistant Acinetobacter baumannii prosthetic joint infection

Cited by 16 publications

References 19 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

Place in Therapy of the Newly Available Armamentarium for Multi-Drug-Resistant Gram-Negative Pathogens: Proposal of a Prescription Algorithm

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

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