Evolution and Transmission of Cefiderocol-Resistant <i>Acinetobacter baumannii</i> During an Outbreak in the Burn Intensive Care Unit

Smoke, Steven; Brophy, Alison; Reveron, Samuel; Iovleva, Alina; Kline, Ellen G; Marano, Michael A.; Miller, Lincoln P.; Shields, Ryan K.

doi:10.1093/cid/ciac647

Cited by 30 publications

(30 citation statements)

References 17 publications

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“…Resistance to β-lactamases activity together with the “Trojan horse” entry strategy into bacterial cells represent the strengths of the recently approved siderophore-cephalosporin cefiderocol. Although surveillance studies have reported potent activity with low MIC90 and MIC50 values, even on MDR isolates, reports of cefiderocol resistance are steadily increasing [ 11 , 12 , 13 , 14 , 15 , 16 ]. The combination of several mechanisms, including mutations affecting function of siderophore receptors and expression of certain β-lactamases, seems to be the main cause of resistance to cefiderocol [ 9 ].…”

Section: Discussionmentioning

confidence: 99%

Synergistic Effect of Clinically Available Beta-Lactamase Inhibitors Combined with Cefiderocol against Carbapenemase-Producing Gram-Negative Organisms

et al. 2022

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The role of β-lactamases in reduced susceptibility or resistance to cefiderocol has been supported by recent reports. The purpose of this study was to investigate the in vitro impact of clinically available β-lactamase inhibitors on cefiderocol activity against characterized carbapenemase-producing Gram-negative isolates. A collection of 39 well-characterized Gram-negative isolates obtained from various clinical sources and countries were included. Cefiderocol antimicrobial susceptibility was evaluated via reference broth microdilution. The chequerboard microdilution method and time–kill assays were used to determine the synergy of tazobactam, avibactam, vaborbactam and relebactam in combination with cefiderocol. MICs of cefiderocol presented a 4- to 256-fold reduction against Klebsiella pneumoniae carbapenemase (KPC)-producing Gram-negative isolates (predominantly K. pneumoniae) when avibactam, vaborbactam and relebactam were combined individually. Notably, the KPC-inhibitors led to a 4- to 32-fold reduction in cefiderocol MICs in the four cefiderocol-resistant KPC-producing K. pneumoniae isolates, showing restoration of cefiderocol susceptibility (MIC ≤ 2 mg/L) in ten out of twelve cases. Tazobactam led to a 4- to 64-fold decrease in cefiderocol MICs only in K. pneumoniae strains harbouring blaKPC-41, blaKPC-31, blaKPC-53 and blaKPC-66. The synergistic effect of all serine-β-lactamase inhibitors on cefiderocol activity was also shown in OXA-48-like-producing Enterobacterales strains. Conversely, a combination of β-lactamases inhibitors with cefiderocol was not synergistic with all OXA-23-like-producing strains and most metallo-β-lactamases producers. In conclusion, the addition of clinically available serine β-lactamase inhibitors to cefiderocol might represent an important development in the formulation to increase its spectrum and therapeutic efficacy, and to limit in vivo resistance emergence.

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Section: Discussionmentioning

confidence: 99%

Synergistic Effect of Clinically Available Beta-Lactamase Inhibitors Combined with Cefiderocol against Carbapenemase-Producing Gram-Negative Organisms

et al. 2022

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“…Although surveillance studies have reported potent activity with low MIC90 and MIC50 values, even on MDR isolates, reports of cefiderocol resistance are steadily increasing [ 11 , 12 , 13 ]. The combination of several mechanisms, including β-lactamases and mutations affecting siderophore receptor expression or function, appears to be the main cause of reduced susceptibility or resistance to cefiderocol [ 14 ].…”

Section: Discussionmentioning

confidence: 99%

“…Cefiderocol has been evaluated in large international surveillance studies, revealing promising activity against carbapenem-resistant Gram-negative isolates [ 10 ]. However, reports on cefiderocol resistance are steadily increasing [ 11 , 12 , 13 ].…”

Section: Introductionmentioning

confidence: 99%

Disc Diffusion and ComASP® Cefiderocol Microdilution Panel to Overcome the Challenge of Cefiderocol Susceptibility Testing in Clinical Laboratory Routine

et al. 2023

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Cefiderocol susceptibility testing represents a major challenge for clinical microbiology. Although disc diffusion showed robustness to test cefiderocol susceptibility, large areas of technical uncertainty (ATU) are reported by current EUCAST breakpoints. Herein, we evaluated the in vitro activity of cefiderocol on a collection of 286 difficult-to-treat Gram-negative isolates using disc diffusion and ComASP® cefiderocol microdilution panel. Broth microdilution (BMD) in iron-depleted Mueller–Hinton broth was used as reference method. Following the EUCAST guidelines, disc diffusion allowed to determine cefiderocol susceptibility (susceptible or resistant) in 78.6%, 88.1%, 85.4% and 100% of Enterobacterales, P. aeruginosa, A. baumannii and S. maltophilia isolates tested, respectively. ComASP® cefiderocol panel showed 94% and 84% of overall categorical agreement and essential agreement. Only one very major error and two major errors were observed, for MIC values nearly close to the resistance breakpoint (2 mg/L). Overall, 20.5% of the carbapenemase-producing Enterobacterales that achieved ATU results by the disc diffusion method tested resistant by both ComASP® panel and reference BMD. Conversely, all VIM-producing P. aeruginosa showed MIC values in the susceptible range (≤2 mg/L). Lastly, only six out of seven (85.7%) A. baumannii isolates showing inhibition zones <17 mm tested resistant by both ComASP® panel and the reference BMD suggesting that inhibition zone <17 mm are not unequivocally suggestive of resistance. Our results, although obtained on a limited number of isolates, suggest that the combination of disc diffusion with a ComASP® cefiderocol microdilution panel could be a viable solution to overcome the challenge of cefiderocol susceptibility testing in routine microbiology laboratories.

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“…Because of the abuse of antibiotics, A baumannii was resistant to multiple antibiotics, named “Multiple Resistance Acinetobacter Baumannii .” [18] A baumannii infection could result in death in an intensive unit. [19–23]…”

Section: Discussionmentioning

confidence: 99%

Correlative factor of death in patients with infected pancreatic necrosis after surgical intervention

Chen

Liu

Cai

2022

Journal of Pancreatology

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Background: Acute pancreatitis (AP) was a potentially fatal disease with a variation in severity. Infected pancreatic necrosis was a common complication in AP which needed surgical intervention. The present study was to study the correlative factors of death in patients with infected pancreatic necrosis after surgical intervention. Methods: From January 2016 to October 2019, a total of 186 patients with infected pancreatic necrosis after surgical intervention in the First Medical Center, Chinese PLA General Hospital were retrospectively enrolled in this study. Of the 186 patients, 22 who died in the hospital were defined as a mortality group and the others as a survival group. The clinical characteristic of the 2 groups was compared and the relative risk of mortality in patients with infected pancreatic necrosis after the surgical intervention was studied. Results: Acute fluid collection, acute kidney injury, acute lung injury, acute liver injury, multiple organ dysfunction syndromes, abdominal bleeding, abdominal Acinetobacter baumannii infection, pulmonary infection, pulmonary A baumannii infection, positive blood culture, A baumannii of blood culture, severe acute pancreatitis according to Atlanta 2012, the use of continuous renal replacement therapy, mechanical ventilation and minimally invasive retroperitoneal pancreatic necrosectomy was associated with death in hospital. Older age, longer acute kidney injury lasting time, longer acute lung injury lasting time, longer acute liver injury lasting time, and longer multiple organ dysfunction syndromes lasting time in predicting mortality in patients with infected pancreatic necrosis after surgical intervention were (0.

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Evolution and Transmission of Cefiderocol-Resistant Acinetobacter baumannii During an Outbreak in the Burn Intensive Care Unit

Cited by 30 publications

References 17 publications

Synergistic Effect of Clinically Available Beta-Lactamase Inhibitors Combined with Cefiderocol against Carbapenemase-Producing Gram-Negative Organisms

Synergistic Effect of Clinically Available Beta-Lactamase Inhibitors Combined with Cefiderocol against Carbapenemase-Producing Gram-Negative Organisms

Disc Diffusion and ComASP® Cefiderocol Microdilution Panel to Overcome the Challenge of Cefiderocol Susceptibility Testing in Clinical Laboratory Routine

Correlative factor of death in patients with infected pancreatic necrosis after surgical intervention

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