In vitro and in vivo efficacy of cefiderocol plus tigecycline, colistin, or meropenem against carbapenem-resistant Acinetobacter baumannii

Ni, Wentao; Wang, Yifan; Ma, Xinqian; He, Yukun; Zhao, Junlong; Guan, Jie; Li, Yanjun; Gao, Zhancheng

doi:10.1007/s10096-022-04503-7

Cited by 10 publications

(9 citation statements)

References 19 publications

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“…Cefiderocol acquired bactericidal activity only when combined with avibactam (in K. pneumoniae N859 ( bla KPC-50 ) and K. pneumoniae N1091 ( bla OXA-48 )) and with relebactam (in K. pneumoniae N859 ( bla KPC-50 )). In agreement with our results, Ni et al observed regrowth of A. baumannii after 6 h of treatment with 1× MIC cefiderocol monotherapy in time–kill assays, in isolates both susceptible and resistant to cefiderocol [ 26 ].…”

Section: Discussionsupporting

confidence: 93%

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: Discussionsupporting

confidence: 93%

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 two antibiotics tigecycline and colistin remained effective throughout the study period. According to previous evidence (80)(81)(82)(83)(84), combinations of these two antibiotics or combination of at least one of them with a third antibiotic have been used in treatment of MDR Acinetobacter infections, with variable success. However, both antibiotics remain among the most effective antimicrobial agents against Acinetobacter isolates in vitro (85), and their value needs to be preserved.…”

Section: Discussionmentioning

confidence: 99%

Epidemiology and antimicrobial resistance trends of Acinetobacter species in the United Arab Emirates: a retrospective analysis of 12 years of national AMR surveillance data

Thomsen,

Abdulrazzaq,

AlRand

2024

Front. Public Health

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IntroductionAcinetobacter spp., in particular A. baumannii, are opportunistic pathogens linked to nosocomial pneumonia (particularly ventilator-associated pneumonia), central-line catheter-associated blood stream infections, meningitis, urinary tract infections, surgical-site infections, and other types of wound infections. A. baumannii is able to acquire or upregulate various resistance determinants, making it frequently multidrug-resistant, and contributing to increased mortality and morbidity. Data on the epidemiology, levels, and trends of antimicrobial resistance of Acinetobacter spp. in clinical settings is scarce in the Gulf Cooperation Council (GCC) and Middle East and North Africa (MENA) regions.MethodsA retrospective 12-year analysis of 17,564 non-duplicate diagnostic Acinetobacter spp. isolates from the United Arab Emirates (UAE) was conducted. Data was generated at 317 surveillance sites by routine patient care during 2010–2021, collected by trained personnel and reported by participating surveillance sites to the UAE National AMR Surveillance program. Data analysis was conducted with WHONET.1ResultsSpecies belonging to the A. calcoaceticus-baumannii complex were mostly reported (86.7%). They were most commonly isolated from urine (32.9%), sputum (29.0%), and soft tissue (25.1%). Resistance trends to antibiotics from different classes during the surveillance period showed a decreasing trend. Specifically, there was a significant decrease in resistance to imipenem, meropenem, and amikacin. Resistance was lowest among Acinetobacter species to both colistin and tigecycline. The percentages of multidrug-resistant (MDR) and possibly extensively drug-resistant (XDR) isolates was reduced by almost half between the beginning of the study in 2010 and its culmination in 2021. Carbapenem-resistant Acinetobacter spp. (CRAB) was associated with a higher mortality (RR: 5.7), a higher admission to ICU (RR 3.3), and an increased length of stay (LOS; 13 excess inpatient days per CRAB case), as compared to Carbapenem-susceptible Acinetobacter spp.ConclusionCarbapenem-resistant Acinetobacter spp. are associated with poorer clinical outcomes, and higher associated costs, as compared to carbapenem-susceptible Acinetobacter spp. A decreasing trend of MDR Acinetobacter spp., as well as resistance to all antibiotic classes under surveillance was observed during 2010 to 2021. Further studies are needed to explore the reasons and underlying factors leading to this remarkable decrease of resistance over time.

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“…Italian societies’ guidelines request further studies to consolidate recommendations on CFD use and evaluate the use of this drug as monotherapy or in a combination therapy regimen with other antibiotics [ 8 ]. The rationale of CFD use in combination therapy regimens is based on in vitro data on the potential benefit of adding a different class antimicrobial agent to overcome the non-susceptibility of CR-GN to CFD [ 30 , 31 , 32 ]. Furthermore, keeping in mind the difficulties of obtaining reliable CFD-susceptibility tests, as highlighted by Eucast [ 33 ], recent studies suggest the possibility of underestimating heteroresistant subpopulations and in vivo developed resistance due to inoculum effect [ 34 , 35 ]; this outlook assumes the use of combination therapy regimens in infections at high risk of suboptimal antibiotic exposure, such as cIAIs, osteomyelitis and particular cases of difficult-to-treat VAPs.…”

Section: Discussionmentioning

confidence: 99%

Cefiderocol Efficacy in a Real-Life Setting: Single-Centre Retrospective Study

et al. 2023

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The current carbapenem-resistant gram-negative bacteria (CR-GN) treatment guidelines lack strong evidence about cefiderocol (CFD) efficacy against CR-GN, especially CRAB. The study’s purpose is to evaluate the effectiveness of CFD in a real-life setting. We made a single-center retrospective study of 41 patients who received CFD in our hospital for several CR-GN infections. Bloodstream infections (BSI) affected 43.9% (18/41) of patients, while CRAB affected 75.6% (31/41) of isolated CR-GN patients. Thirty-days (30-D) all-causes mortality affected 36.6% (15/41) of patients, while end-of-treatment (EOT) clinical cure affected 56.1% (23/41). Finally, microbiological eradication at EOT affected 56.1% (23/41) of patients. Univariate and multivariate analysis showed that septic shock is an independent factor associated with mortality. Subgroup analyses showed no difference in CFD effectiveness between monotherapy and combination therapy.

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In vitro and in vivo efficacy of cefiderocol plus tigecycline, colistin, or meropenem against carbapenem-resistant Acinetobacter baumannii

Cited by 10 publications

References 19 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

Epidemiology and antimicrobial resistance trends of Acinetobacter species in the United Arab Emirates: a retrospective analysis of 12 years of national AMR surveillance data

Cefiderocol Efficacy in a Real-Life Setting: Single-Centre Retrospective Study

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