Table 4.
In vivo efficacy and pharmacodynamics of fosfomycin, amikacin and gentamicin, alone and in combination, for the experimental peritoneal sepsis model.
| Strains | Treatment group | n | Spleen log10 cfu/g (mean ± SD) | Bacteremia (%) | Mortality (%) | Cmax/MIC | fCmax/MIC | AUC0−24/MIC | fAUC0−24/MIC |
|---|---|---|---|---|---|---|---|---|---|
| VIM-1 | CTL | 10 | 8.98 ± 0.46 | 100 | 100 | ND | ND | ND | ND |
| FOF | 13 | 7.23 ± 0.48a | 100 | 100 | 21.16 | 20.95 | 42.11 | 41.69 | |
| AK | 15 | 5.36 ± 2.46a | 40a, b | 80 | 35.93 | 27.93 | 85.24 | 63.06 | |
| FOF+AK | 14 | 6.62 ± 0.38a, b | 28.57a, b | 100 | ND | ND | ND | ND | |
| VIM-1/DHA-1 | CTL | 10 | 9.46 ± 0.32 | 100 | 100 | ND | ND | ND | ND |
| FOF | 15 | 8.64 ± 0.94 | 100 | 93.3 | 42.32 | 41.89 | 84.23 | 83.39 | |
| AK | 15 | 8.60 ± 1.48 | 100 | 86.67 | 8.98 | 6.98 | 21.31 | 15.77 | |
| FOF+AK | 15 | 8.43 ± 1.36 | 100 | 93.33 | ND | ND | ND | ND | |
| OXA-48 plus CTX-M-15 | CTL | 10 | 9.56 ± 0.47 | 100 | 100 | ND | ND | ND | ND |
| FOF | 15 | 8.05 ± 0.30a | 100 | 100 | 21.16 | 20.95 | 42.11 | 41.69 | |
| AK | 14 | 7.83 ± 1.07a | 78.57 | 78.57 | 35.93 | 27.93 | 85.24 | 63.06 | |
| FOF+AK | 15 | 7.74 ± 0.67a | 80 | 100 | ND | ND | ND | ND | |
| KPC-3 (TEM-1 and SHV-11) | CTL | 10 | 10.19 ± 0.29 | 100 | 100 | ND | ND | ND | ND |
| FOF | 15 | 9.86 ± 0.24 | 100 | 100 | 21.16 | 20.95 | 42.11 | 41.69 | |
| GEN | 15 | 9.14 ± 2.39 | 100 | 86.67 | 10.06 | 7.36 | 20.12 | 14.08 | |
| FOF+GEN | 15 | 9.02 ± 0.68a, b | 100 | 93.33 | ND | ND | ND | ND |
CTL, control (no antimicrobial treatment); FOF, fosfomycin; AK, amikacin; GEN, gentamicin.
a
P ≤ 0.05 compared to CTL groups.
b
P ≤ 0.05 compared to FOF groups.
ND, no determined. VIM-1 and OXA-48 plus CTX-M-15 strains, AMK MIC: 1 mg/L; VIM-1 (DHA-1) AMK MIC: 4 mg/L; KPC-3 (TEM-1 and SHV-11) GEN MIC: 2 mg/L.
Bold tries to remark the treatments that were significantly better than controls and other treatments.