Evaluating Cefiderocol in the Treatment of Multidrug-Resistant Gram-Negative Bacilli: A Review of the Emerging Data

Giacobbe, Daniele Roberto; Ciacco, Eugenio; Girmenia, Corrado; Pea, Federico; Rossolini, Gian María; Sotgiu, Giovanni; Tascini, Carlo; Tumbarello, Mario; Viale, Pierluigi; Bassetti, Matteo

doi:10.2147/idr.s205309

Cited by 25 publications

(18 citation statements)

References 72 publications

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“…From a clinical point of view, few antibiotic treatments retain activity against VIM-producing microorganisms: aminoglycosides, IV and/or nebulised colistin, tigecyline and the recently described cefiderocol [ [21] , [22] , [23] ]. However, the use of cefiderocol was limited by its availability as a non-marketed product at the time of the outbreak.…”

Section: Discussionmentioning

confidence: 99%

Nosocomial outbreak of monoclonal VIM carbapenemase-producing Enterobacter cloacae complex in an intensive care unit during the COVID-19 pandemic: an integrated approach

Mullié

Lemonnier

Adjidé

et al. 2022

Journal of Hospital Infection

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Section: Discussionmentioning

confidence: 99%

Nosocomial outbreak of monoclonal VIM carbapenemase-producing Enterobacter cloacae complex in an intensive care unit during the COVID-19 pandemic: an integrated approach

Mullié

Lemonnier

Adjidé

et al. 2022

Journal of Hospital Infection

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“…It is important to highlight that two out of three patients treated with cefiderocol monotherapy experienced microbiological relapse and one of them (P3) reported an MIC creep. Currently, there is still no agreement about how to use cefiderocol, whether in monotherapy 12 or in combinations, 11 , 15 and further studies are needed.…”

Section: Discussionmentioning

confidence: 99%

Real-life experience with compassionate use of cefiderocol for difficult-to-treat resistant Pseudomonas aeruginosa (DTR-P) infections

Meschiari

Volpi

Faltoni

et al. 2021

JAC-Antimicrobial Resistance

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Objectives To describe our real-life experience with cefiderocol in XDR and difficult-to-treat resistant Pseudomonas aeruginosa (DTR-P) infections without any other available treatment options. Methods We included patients with a proven infection due to an XDR/DTR-P, who had failed on previous regimens, and were treated with cefiderocol, following them prospectively to day 90 or until hospital discharge or death. Results Seventeen patients treated for >72 h with cefiderocol were included: 14 receiving combination regimens (82.4%) and 3 receiving monotherapy (17.6%). Fourteen patients were males (82%) with a median age of 64 years (IQR 58–73). Fifteen patients (88.2%) were admitted to the ICU and five had septic shock (29%). Seven cases (41.2%) were ventilator-associated pneumonia, of which 71% (5/7) occurred in COVID-19 patients. Four were complicated intrabdominal infections, one ecthyma gangrenosum, one nosocomial pneumonia and one empyema, one osteomyelitis, one primary bacteraemia, and one nosocomial external ventricular drainage meningitis. Clinical cure and microbiological cure rates were 70.6% and 76.5%, respectively. There were six deaths (35.3%) after a median of 8 days (IQR 3–10) from the end of treatment, but only two of them (11.7%) were associated with P. aeruginosa infection progression. Conclusions Our experience collecting this large case series of DTR-P treated with cefiderocol may help clinicians consider this new option in this hard-to-manage setting. Our results are even more relevant in the current scenario of ceftolozane/tazobactam shortage. Importantly, this is the first study providing real-life data indicating adequate cefiderocol concentrations in CSF.

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“… 76 This latter recommendations is justified by the fact that the overall susceptibility rate of cefiderocol against NDM-producing Enterobacterales is <70%, and MIC 50 /MIC 90 are 2–4-fold higher compared to VIM- or IMP-producing strains. 89 , 102 , 112 , 113 Fosfomycin combined with high-dose meropenem could represent a valuable alternative against both types of MBL-producing Enterobacterales infections.…”

Section: Overview Of Recommendationsmentioning

confidence: 99%

An Evidence-Based Multidisciplinary Approach Focused at Creating Algorithms for Targeted Therapy of BSIs, cUTIs, and cIAIs Caused by Enterobacterales in Critically Ill Adult Patients

Gatti¹,

Viaggi²,

Rossolini³

et al. 2021

IDR

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Prompt implementation of appropriate targeted antibiotic therapy represents a valuable approach in improving clinical and ecological outcome in critically septic patients. This multidisciplinary opinion article focused at developing evidence-based algorithms for targeted antibiotic therapy of bloodstream (BSIs), complicated urinary tract (cUTIs), and complicated intrabdominal infections (cIAIs) caused by Enterobacterales . The aim was to provide a guidance for intensive care physicians either in appropriately placing novel antibiotics or in considering strategies for sparing the broadest-spectrum antibiotics. A multidisciplinary team of experts (one intensive care physician, one infectious disease consultant, one clinical microbiologist and one MD clinical pharmacologist), performed several rounds of assessment to reach agreement in developing six different algorithms according to the susceptibility pattern (one each for multi-susceptible, extended-spectrum beta-lactamase-producing, AmpC beta-lactamase-producing, Klebsiella pneumoniae carbapenemase (KPC)-producing, OXA-48-producing, and Metallo-beta-lactamase (MBL)-producing Enterobacterales ). Whenever multiple therapeutic options were feasible, a hierarchical scale was established. Recommendations on antibiotic dosing optimization were also provided. In order to retrieve evidence-based support for the therapeutic choices proposed in the algorithms, a comprehensive literature search was performed by a researcher on PubMed-MEDLINE from inception until March 2021. Quality and strength of evidence was established according to a hierarchical scale of the study design. Only articles published in English were included. It is expected that these algorithms, by allowing prompt revision of antibiotic regimens whenever feasible, appropriate place in therapy of novel beta-lactams, implementation of strategies for sparing the broadest-spectrum antibiotics, and pharmacokinetic/pharmacodynamic optimization of antibiotic dosing regimens, may be helpful either in improving clinical outcome or in containing the spread of antimicrobial resistance.

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Evaluating Cefiderocol in the Treatment of Multidrug-Resistant Gram-Negative Bacilli: A Review of the Emerging Data

Abstract: On behalf of the ISGRI-SITA (Italian Study Group on Resistant Infections of the Italian Society of Anti-infective Therapy)

Cited by 25 publications

References 72 publications

Nosocomial outbreak of monoclonal VIM carbapenemase-producing Enterobacter cloacae complex in an intensive care unit during the COVID-19 pandemic: an integrated approach

Nosocomial outbreak of monoclonal VIM carbapenemase-producing Enterobacter cloacae complex in an intensive care unit during the COVID-19 pandemic: an integrated approach

Real-life experience with compassionate use of cefiderocol for difficult-to-treat resistant Pseudomonas aeruginosa (DTR-P) infections

An Evidence-Based Multidisciplinary Approach Focused at Creating Algorithms for Targeted Therapy of BSIs, cUTIs, and cIAIs Caused by Enterobacterales in Critically Ill Adult Patients

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