Article Figures & Data
Figures
- FIG 1
Correlation of PK/PD parameters with efficacy for cefiderocol (a) and cefepime (b) in a neutropenic murine thigh infection model in which infection is caused by Pseudomonas aeruginosa SR27016. Treatment was initiated at 2 h postinfection. Cefiderocol and cefepime were subcutaneously administered once daily (q24h), twice daily (q12h), 4 times a day (q6h), and 8 times a day (q3h). Each point represents data for each mouse. R2, square of the correlation coefficient.
- FIG 2
Comparison of the %fT>MIC of cefiderocol between MIC values in ID-CAMHB and CAMHB in neutropenic murine thigh and lung infection models.
- FIG 3
Magnitude of the %fT>MIC required for the efficacy of cefiderocol against multiple strains of Enterobacteriaceae and nonfermenters in the neutropenic murine thigh (a) and neutropenic lung infection (b) models.
Tables
- TABLE 1
MICs of cefiderocol, cefepime, and meropenem against the tested strains
Organism Type of carbapenemase Infection model applied in this study MIC (μg/ml) Cefiderocol Cefepime Meropenem ID-CAMHB CAMHB E. coli ATCC 25922 —d Thigh 0.125 0.25 0.125 ≤ 0.031 AB NDM-4 Lung 4 8 >32 32 IR-5 NDM-1 Lung 4 4 >32 >32 K. pneumoniae ATCC 13883 — Thigh 0.25 0.5 0.063 ≤ 0.031 1478266 — Thigh 0.5 1 0.063 0.063 1478677 — Thigh 0.25 0.25 >32 0.125 VA-357a KPC-2 Thigh, lung 2 8 >32 32 VA-361a KPC-2 Lung 4 16 >32 16 VA-384a KPC-2 Thigh, lung 4 16 >32 >32 VA-391a KPC-3 Thigh, lung 4 16 >32 16 6560-MARb NDM-1 Thigh, lung 2 2 >32 32 KI2c NDM-1 Thigh, lung 8 32 >32 >32 NCTC 13443 NDM-1c Thigh, lung 16 256 >32 >32 P. aeruginosa SR27016 — Thigh 0.25 0.25 1 0.5 ATCC 27853 — Thigh, lung 0.5 2 2 0.25 SR27001 IMP-1 Thigh, lung 2 32 >32 >32 NCTC 13437 VIM-10 Lung 1 8 >32 >32 A. baumannii BEN ST BRI OXA-24 Lung 0.25 2 >32 >32 1485247 — Lung 2 32 >32 8 NCTC 13301 OXA-23 Lung 1 32 >32 32 S. maltophilia 1146824 Not tested Lung 0.125 0.125 >32 >32 1371071 Not tested Lung 0.125 0.125 >32 >32 1392567 Not tested Lung 0.25 0.25 >32 >32 1444463 Not tested Lung 0.25 0.125 >32 >32 - TABLE 2
PK parameters of cefiderocol and cefepime following a single subcutaneous administration to neutropenic mice infected with P. aeruginosa SR27016
Compound Infection model Dose (mg/kg) Cmax (μg/ml) t1/2a (h) CL/F (ml/h/kg) Cefiderocol Thigh 4 4.42 0.43 882 Thigh 40 50.6 0.50 801 Thigh 400 381 0.56 934 Lung 4 4.01 1.20 805 Lung 40 41.7 0.28 670 Lung 400 310 0.57 921 Lung 600 386 0.44 972 Cefepime Thigh 10 14.3 0.45 798 Thigh 100 145 0.23 853 Thigh 1,000 808 0.74 1,029 ↵a t1/2, half-life.
