TABLE 2.
In vivo efficacy of MK-826 and other agents against gram-positive organisms in a murine systemic infection model
| Challenge strain | Com- pound | MICa (μg/ml) | ED50 (95% CL)b |
|---|---|---|---|
| S. aureus MB2985 (MSSA)c | MK-826 | 0.125 | 1.580 (0.800–3.100) |
| IPM | 0.008 | 0.038 (0.022–0.066) | |
| CEF | 0.250 | 0.460 (0.260–0.800) | |
| FEP | 1.000 | 2.940 (1.490–5.800) | |
| CID | 1.000 | 6.620 (3.360–13.060) | |
| CTRX | 2.000 | 6.250 (ND) | |
| S. pneumoniae MB212d | MK-826 | 0.031 | 0.156 (ND) |
| IPM | 0.004 | 0.052 (0.030–0.090) | |
| FEP | 0.016 | 0.432 (0.140–1.310) | |
| CTRX | 0.016 | 0.094 (0.050–0.160) | |
| S. pneumoniae MCL4997c | MK-826 | 0.125 | 3.190 (1.330–7.660) |
| IPM | 0.062 | 8.010 (3.330–19.240) | |
| CTRX | 0.500 | 3.300 (1.920–5.820) | |
| PEN | 0.500 | 15.110 (8.680–26.300) | |
| S. pneumoniae MCL4983d | MK-826 | 2.000 | 12.500 (ND) |
| IPM | 0.250 | 5.230 (3.010–9.110) | |
| CTRX | 1.000 | 10.340 (5.940–18.010) | |
| PEN | 2.000 | 85.430 (43.320–168.480) | |
| S. pneumoniae MCL5631c | MK-826 | 2.000 | 12.500 (ND) |
| IPM | 0.500 | 2.450 (1.240–4.840) | |
| CTRX | 2.000 | 5.900 (3.000–11.600) | |
| PEN | 4.000 | 41.400 (23.760–72.040) | |
| S. pyogenes MB2874d | MK-826 | 0.008 | 0.059 (0.030–0.116) |
| IPM | 0.004 | 0.012 (0.006–0.023) | |
| FEP | 0.016 | 0.100 (0.042–0.240) | |
| CTRX | 0.016 | 0.120 (0.055–0.263) |
a
MIC determined by procedures recommended by the National Committee for Clinical Laboratory Standards (14).
b
The ED50 (calculated on day 7) that protects 50% of infected mice and the 95% confidence limit (95% CL) (both in milligrams per kilogram) are reported. ND, not defined.
c
Challenge with test organism (0.5 ml; i.p.) and treatment (0.5 ml; s.c.) begun immediately after infection (total of 1 dose).
d
Challenge with test organism (0.5 ml; i.p.) and treatment (0.5 ml; s.c.) begun immediately and 4 h after infection (total of 2 doses).