Article Figures & Data
Figures
- FIG. 1.
Efficacy of AM 7359 and linezolid (Lin) against an MRSA COL strain in a localized infection model. DBA/2 mice (five per group) were challenged intramuscularly with 3.6 × 108 CFU of MRSA in a 0.2-ml inoculum and treated p.o. three times a day for 1 day and once a day for 5 days or i.v. three times a day for 1 day and once a day for 1 day.
- FIG. 2.
Efficacy of AM 7359 and linezolid against an LMRSA strain in a localized infection model. C3H mice (five per group) were challenged intramuscularly with 109 CFU of LMRSA in a 0.2-ml inoculum and treated p.o. three times a day for 1 day and once a day for 5 days.
Tables
- TABLE 1.
Comparative efficacies of AM 7359 and linezolid against MSSA Smith in an organ burden assay
Compound (mode of administration) and MIC (μg/ml) Dose (mg/kg/day) % Mortalitya Log CFU/g of kidneyb (% eradication) Reduction (SD)c AM 7359 (p.o.), 0.125 25 0 3.11* (0) 5.23 (0.58) 12.5 0 5.41* (0) 2.93 (0.59) 6.25 0 5.71* (0) 2.63 (0.80) 3.12 0 8.60 (0) −0.26 (0.37) Linezolid (p.o.), 2.0 25 0 2.27* (100) 6.07 (0.04) 12.5 0 5.63* (0) 2.71 (0.37) 6.25 0 6.90* (0) 1.44 (0.59) 3.12 0 8.87 (0) −0.53 (0.10) AM 7359 (i.v.), 0.125 25 0 3.81* (0) 4.59 (0.15) 12.5 0 3.94* (0) 4.46 (0.16) 6.25 0 6.37* (0) 2.03 (0.61) 3.12 0 8.34 (0) 0.06 (0.15) Linezolid (i.v.), 2.0 25 0 4.13* (0) 4.27 (0.70) 12.5 0 6.96* (0) 1.44 (1.62) 6.25 0 8.52 (0) −0.12 (0.20) 3.12 0 8.67 (0) −0.27 (0.11) Control (distilled H2O; p.o.) 20 8.34 (0) Control (distilled H2O; i.v.) 0 8.40 (0) ↵ a Calculated as the number dead divided by the total number in the group.
↵ b *, significant reduction compared to sham-treated control as determined by Student's t test.
↵ c Reduction in log number of CFU compared to sham-treated control. Significant reductions are shown in bold. SD, standard deviation of results for the four mice per group.
- TABLE 2.
ED99 of AM 7359 and linezolid in mouse efficacy models
Model (organism) ED99 (mg/kg) (95% CI) of: AM 7359 Linezolid p.o. i.v. p.o. i.v. Kidney (MSSA)a 4.9 (3.1-7.6) 6.3 (4.2-9.5) 7.0 (5.3-9.2) 12 (7.8-18.5) Thigh (MRSA)b 4.2 (2.8-6.1) 5.6 (2.3-∞) 5.2 (4.2-6.6) 6.9 (4.5-∞) Thigh (LMRSA) 10.2 (4.3-24) NTa 85 (50.2-∞) NT ↵ a Values are based on mice receiving a single dose 15 min postchallenge; therefore, ED99 values are equal to the total mg/kg/day given each mouse.
↵ b Orally dosed mice received a total of eight doses in 5 days and i.v. dosed mice a total of four doses in 24 h; therefore, the ED99 values represent the value of each individual dose given in each model.
c NT, not tested.
