TABLE 5.
Activity of meropenem alone and in combination with vaborbactam against carbapenem-resistant KPC-containing K. pneumoniae in a neutropenic mouse thigh infection modela
| K. pneumoniae strain | Compound | Dose (mg/kg) | Log CFU/thigh ± SDb | P valuec |
|---|---|---|---|---|
| KP1004 | Untreated control at start of treatment | 0 | 7.24 ± 0.10 | |
| Untreated control at 24 h | 0 | Not done | ||
| Meropenem alone | 300.00 | 7.18 ± 0.14 | 0.298 vs NT; <0.0001 vs combo | |
| Meropenem (with vaborbactam) | 300 (+50) | 5.55 ± 0.18 | <0.0001 vs NT; <0.0001 vs alone | |
| KP1074 | Untreated control at start of treatment | 0 | 7.06 ± 0.25 | |
| Untreated control at 24 h | 0 | Not done | ||
| Meropenem alone | 300 | 8.07 ± 0.43 | 0.0002 vs NT; 0.0001 vs combo | |
| Meropenem (with vaborbactam) | 300 (+50) | 5.85 ± 0.25 | 0.0005 vs NT; 0.0001 vs alone | |
| KP1099 | Untreated control at start of treatment | 0 | 7.03 ± 0.02 | |
| Untreated control at 24 h | 0 | 9.22 ± 0.6 | ||
| Meropenem alone | 300 | 8.78 ± 0.29 | <0.0001 vs NT; <0.0001 vs combo | |
| Meropenem (with vaborbactam) | 300 (+50) | 5.78 ± 0.53 | 0.00132vs NT; <0.0001 vs alone | |
| KP1100 | Untreated control at start of treatment | 0 | 6.75 ± 0.59 | |
| Untreated control at 24 h | 0 | 9.13 ± 0.13 | ||
| Meropenem alone | 300 | 6.36 ± 0.17 | 0.0002 vs NT; <0.0001 vs combo | |
| Meropenem (with vaborbactam) | 300 (+50) | 5.93 ± 0.28 | 0.043 vs NT; <0.0001 vs alone | |
| KP1093 | Untreated control at start of treatment | 0 | 6.76 ± 0.10 | |
| Untreated control at 24 h | 0 | 8.69 ± 0.29 | ||
| Meropenem alone | 300 | 7.34 ± 0.19 | 0.0017vs NT; <0.0001 vs combo | |
| Meropenem (with vaborbactam) | 300 (+50) | 4.90 ± 0.15 | <0.0001vs NT; <0.0001 vs alone | |
| KP1094 | Untreated control at start of treatment | 0 | 6.70 ± 0.17 | |
| Untreated control at 24 h | 0 | 8.76 ± 0.31 | ||
| Meropenem alone | 300 | 6.80 ± 0.56 | 0.733 vs NT; 0.0033 vs combo | |
| Meropenem (with vaborbactam) | 300 (+50) | 4.33 ± 0.89 | 0.0019 vs NT; 0.0033 vs alone | |
| KP1223 | Untreated control at start of treatment | 0 | 6.92 ± 0.16 | |
| Untreated control at 24 h | 0 | 9.34 ± 0.18 | ||
| Meropenem alone | 300 | 10.12 ± 0.11 | <0.0001vs NT; <0.0001 vs combo | |
| Meropenem (with vaborbactam) | 300 (+50) | 5.88 ± 0.70 | <0.0001 vs NT; <0.0001 vs alone |
a
Treatment started at 2 h postinfection and continued every 2 h for 24 h. Untreated controls were euthanized at the start of treatment. Treated groups were euthanized 2 h after the last treatment.
b
Those labeled “not done” were due to high mortality rate.
c
NT, untreated at the start of treatment.