Cefiderocol for treatment of an empyema due to extensively drug-resistant Pseudomonas aeruginosa: Clinical observations and susceptibility testing considerations

Kufel, Wesley D; Steele, Jeffrey; Riddell, Scott W.; Jones, Zachary; Shakeraneh, Pegah; Endy, Timothy P.

doi:10.1016/j.idcr.2020.e00863

Cited by 22 publications

(27 citation statements)

References 16 publications

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“…There was no correlation between outcomes and observed MIC increases in the isolates from APEKS-NP and CREDIBLE-CR. 14 , 26 In a recent case report on the compassionate use of cefiderocol for 21 days, a tracheal aspirate sample obtained 10 days after the EOT revealed two morphological variants of an extensively drug-resistant P. aeruginosa isolate, both of which were associated with MIC increases (from 0.25 to 0.5 μg/mL and 1 μg/mL, respectively) 27 ; however, both remained susceptible to cefiderocol treatment according to CLSI criteria.…”

Section: Discussionmentioning

confidence: 99%

Mechanisms of Reduced Susceptibility to Cefiderocol Among Isolates from the CREDIBLE-CR and APEKS-NP Clinical Trials

Nordmann

Shields

Doi

et al. 2022

Microbial Drug Resistance

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The objective of this study was to characterize isolates with reduced susceptibility to cefiderocol in patients receiving cefiderocol for nosocomial pneumonia or carbapenem-resistant infections in the Phase 3 APEKS-NP and CREDIBLE-CR studies. Susceptibility testing of isolates was conducted at a central laboratory, and post-treatment changes were evaluated according to available breakpoints for cefiderocol. Whole-genome sequencing and multilocus sequence typing were performed for isolates to confirm their origin and identify mutations. Five (APEKS-NP) and nine (CREDIBLE-CR) isolates demonstrated a ≥ 4-fold minimum inhibitory concentration (MIC) increase compared with genetically related baseline isolates; most remained susceptible to cefiderocol despite the ≥4-fold MIC increase. Mutations in β-lactamases or penicillin-binding protein (PBP) were identified in 4/14 isolates: one Enterobacter cloacae (amino acid [AA] substitution [A313P] in ACT-17); two Acinetobacter baumannii (one PBP3 AA substitution [H370Y], one with OXA-23 substitutions [N85I and P225S]); and one Pseudomonas aeruginosa (PDC-30 [4AA deletion “TPMA” position 316–319]). Cloning experiments using isogenic Escherichia coli strains containing wild-type and those mutant cephalosporinase enzymes show that the mutant enzymes may contribute to decreased susceptibility to cefiderocol. Pharmacokinetic data were available for nine patients, for whom cefiderocol exposures exceeded 100% f T > 4 × MIC . No clear pattern between mutations and development or extent of MIC increases was observed. No mutations were identified in genes related to iron transport, including fiu , cirA , piuA/C , and pirA , among recovered Gram-negative isolates. APEKS-NP: NCT03032380; CREDIBLE-CR: NCT02714595.

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Section: Discussionmentioning

confidence: 99%

Mechanisms of Reduced Susceptibility to Cefiderocol Among Isolates from the CREDIBLE-CR and APEKS-NP Clinical Trials

Nordmann

Shields

Doi

et al. 2022

Microbial Drug Resistance

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“…Gastrointestinal side effects are the most common (Theuretzbacher et al, 2020, Wu et al, 2020, and neutropenia has been reported with prolonged cefiderocol treatment (Alamarat et al, 2020). AIN attribuTable 1 to cefiderocol has not been reported in any of the previously published clinical cases, nor in the CREDIBLE-CR study (Alamarat et al, 2020, Bassetti et al, 2020, Contreras et al, 2020, Dagher et al, 2020, Edgeworth et al, 2019, Gainey et al, 2020, Kufel et al, 2020, Simeon et al, 2020, Trecharichi et al, 2019, Zingg et al, 2020.…”

Section: Discussionmentioning

confidence: 99%

Cefiderocol treatment of Pseudomonas aeruginosa and extensively drug-resistant Acinetobacter baumannii retained spinal hardware infection causing reversible acute interstitial nephritis

Cipko

Gordon

Adhikari

et al. 2021

International Journal of Infectious Diseases

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This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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“…Follow-up at 12 weeks after end of antibiotic treatment showed full recovery. 45, female 64 Hemangioblastoma requiring multiple neurosurgical interventions, esophageal-pleural fistula, esophageal perforation repaired with jejunostomy and gastrostomy tube placement. Esophageal leak with fistula and growth of cefiderocol-susceptible XDR P. aeruginosa from plural fluid culture, treated surgically and with antibiotic therapy.…”

Section: Case Reports and Case Seriesmentioning

confidence: 99%

“…Case reports and case series of patients with severe GNB infections treated with cefiderocol in compassionate use are detailed in Table 3. [54][55][56][57][58][59][60][61][62][63][64][65][66] All these cases highlight unique challenges in managing patients infected by MDR-GNB including MBL-producing GNB.…”

Section: Case Reports and Case Seriesmentioning

confidence: 99%

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

Giacobbe¹,

Ciacco²,

Girmenia³

et al. 2020

IDR

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Cefiderocol for treatment of an empyema due to extensively drug-resistant Pseudomonas aeruginosa: Clinical observations and susceptibility testing considerations

Cited by 22 publications

References 16 publications

Mechanisms of Reduced Susceptibility to Cefiderocol Among Isolates from the CREDIBLE-CR and APEKS-NP Clinical Trials

Mechanisms of Reduced Susceptibility to Cefiderocol Among Isolates from the CREDIBLE-CR and APEKS-NP Clinical Trials

Cefiderocol treatment of Pseudomonas aeruginosa and extensively drug-resistant Acinetobacter baumannii retained spinal hardware infection causing reversible acute interstitial nephritis

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

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