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. 2020 Jul 22;40(10):901–913. doi: 10.1007/s40261-020-00955-x

Table 3.

Summary of in vitro and animal studies

Year N Authors Inclusion Results
2017 9205 Hackel et al. [24] Gram-negative bacilli collected in SIDERO-WT-2014 Study

MICs ≤ 4 μg/mL

 for 99.9% of all Enterobacteriaceae (MIC90: 0.5–1 μg/mL),

 for 97.0% of meropenem-nonsusceptible Enterobacteriaceae (MIC90: 1–4 μg/mL),

 for 99.9% of all P. aeruginosa isolates (MIC90: 0.5 μg/mL),

 for 100% of meropenem-nonsusceptible P. aeruginosa isolates (MIC90: 0.5 μg/mL),

 for 97.6% of all A. baumannii isolates (MIC90: 1 μg/mL),

 for 96.9% of meropenem-nonsusceptible A. baumannii isolates (MIC90: 1 μg/mL),

 for 100% of isolates of S. maltophilia (MIC90: 0.25–0.5 μg/mL), and

 for 93.8% of B. cepacia isolates
2017 753 Dobias et al. [12] MDR Gram-negative isolates collected from hospitals worldwide were tested against cefiderocol and antibiotic comparators

 MIC90 of 2 mg/L for cefiderocol, MIC90 > 64 mg/L for CT, MEM, CAZ, CZA, and AMK, > 32 mg/L for ATM, > 16 mg/L for FEP, 8 mg/L for CST, and 2 mg/L for TGC

 MIC50 of 0.5 mg/L for cefiderocol, MIC50 > 64 mg/L for CAZ, 64 mg/L for CT, >32 mg/L for ATM, >16 mg/L for FEP, 8 mg/L for MEM and AMK, >4 mg/L for CIP, 1 mg/L for CZA, 0.5 mg/L for TGC, and <0.5 mg/L for CST
2017 471 Falagas et al. [13] Carbapenem-resistant Gram-negative bacteria

MIC90 of 0.5 mg/L

 for A. baumannii and P. aeruginosa, P. stuartii, respectively

MIC90 of 0.5–1 μg/mL

 For Enterobacteriaceae

MIC90 of 1 mg/L

 For K. pneumoniae, E. cloacae, respectively
2018 1873 Hackel et al. [11] Carbapenem-nonsusceptible Enterobacteriaceae, MDR Acinetobacter baumannii, MDR Pseudomonas aeruginosa, Stenotrophomonas maltophilia, and Burkholderia cepacia

MICs ≤4 μg/mL

 for 89.7%, 99.2%, and 100% of isolates of MDR A. baumannii, MDR P. aeruginosa, and S. maltophilia, respectively

MIC90 of 4 μg/mL

 for 90% of carbapenem-nonsusceptible Enterobacteriaceae

MICs of 0.004–8

 for B. cepacian
2019 8954 Karlowsky et al. [7] Gram-negative bacilli (GNB) in SIDERO-WT-2015 Study

MICs ≤ 4 mg/L

 for 99.9% of Enterobacteriaceae, 99.9% of P. aeruginosa, 96.4% of Acinetobacter spp., 99.4% of S. maltophilia, and 94.4% of B. cepacia complex spp.

MICs ≤4 mg/L

 for 99.6% of Enterobacteriaceae, 99.7% of P. aeruginosa, 96.1% of Acinetobacter spp., and 87.1% of B. cepacia complex spp. resistant to meropenem
2019 1272 Kazmierczak et al. [14] Meropenem-non-susceptible isolates of Enterobacteriaceae, Pseudomonas aeruginosa and Acinetobacter baumannii collected as part of the SIDERO-WT-2014 surveillance study

MIC ≤ 4 µg/mL

 for 97.7% of isolates, including 100% of IMP-positive, OXA-58-positive, KPC-positive, VIM-positive, and OXA-48-like-positive isolates; 99.3% of carbapenemase-negative isolates (MIC90: 1 µg/mL); 97.2% of OXA-23-positive isolates (MIC90: 1 µg/mL); 95.2% of OXA-24-positive isolates (MIC90: 1 µg/mL); 91.7% of GES-positive isolates (MIC90: 4 µg/mL); and 64.3% of NDM-positive isolates (MIC90: 8 µg/mL).

MIC ≥8 µg/mL

 for 29 isolates (2.3%; 15 OXA-23-producers, 6 OXA-24-producers, five NDM-producers, and three carbapenemase-negative isolates)
2017 181 Matsumoto et al. [25] Immunocompetent-rat respiratory tract infection models  2 g every 8 h as a 3 h infusion of cefiderocol for 4 days resulted a > 3 log10 reduction in the number of cells of carbapenem-resistant isolates in the lungs
2018 6 Ghazi et al. [27] Murine thigh infection model

 Without cefiderocol, P. aeruginosa bacterial density increased from 5.54 ± 0.23 to 8.68 ± 0.57 log10 CFU in 24 h

 With cefiderocol, > 1 log10 CFU reduction in all eight isolates
2019 5 Nakamura et al. [26] Neutropenic thigh and lung infection models  %fT > MIC best correlates with efficacy of cefiderocol in iron-depleted conditions

P. aeruginosa: Pseudomonas aeruginosa, A. baumannii: Acinetobacter baumannii, S. maltophilia: Stenotrophomonas maltophilia, B. cepacian: Burkholderia cepacian, P. stuartii: Providencia stuartii, K. pneumoniae: Klebsiella pneumoniae, KPC: Klebsiella pneumoniae carbapenemase, E. cloacae: Enterobacter cloacae, CT ceftolozane–tazobactam, CAZ ceftazidime, CZA ceftazidime–avibactam, FEP cefepime, MEM meropenem, CIP ciprofloxacin, ATM aztreonam, AMK amikacin, CST colistin, TGC tigecycline, IMP imipenemase metallo-β-lactamase, VIM Verona integron-mediated metallo-β-lactamase, NDM New Delhi metallo-β-lactamases, OXA oxacillin carbapenemases, MIC minimum inhibitory concentration (μg/mL), MDR multidrug resistant, CFU colony-forming units, %fT > MIC percentage of time that free drug concentrations above the minimum inhibitory concentration