TABLE 3.
In vivo efficacy of MK-826 and other agents against gram-negative organisms in a murine systemic infection model
Challenge strain | Com- pound | MICa (μg/ml) | ED50 (95% CL)b |
---|---|---|---|
E. cloacae MB2646c | MK-826 | 0.500 | 0.227 (ND) |
IPM | 0.250 | 0.062 (0.024–0.161) | |
FEP | 4.000 | 0.235 (0.135–0.410) | |
CTRX | ≥256.000 | 30.400 (17.400–52.900) | |
E. coli MB2884 | MK-826 | 0.008 | 0.022 (ND) |
IPM | 0.125 | 0.172 (ND) | |
FEP | 0.031 | 0.013 (0.006–0.028) | |
CAZ | 0.125 | 0.062 (ND) | |
CTRX | 0.031 | 0.028 (ND) | |
K. pneumoniae MB2883 | MK-826 | ≤0.016 | 0.057 (ND) |
IPM | 0.125 | 6.080 (3.490–10.580) | |
FEP | ≤0.016 | 1.880 (1.080–3.280) | |
CTRX | 0.031 | 0.033 (0.015–0.072) | |
M. morganii MB2833 | MK-826 | 0.008 | 0.034 (0.020–0.060) |
IPM | 2.000 | 3.400 (1.950–5.920) | |
FEP | 0.016 | 0.074 (0.034–0.161) | |
CAZ | 0.125 | 0.318 (0.160–0.630) | |
CTRX | 0.008 | ≤0.018 (ND) | |
P. aeruginosa MB2835 | MK-826 | 1.000 | 1.215 (0.698–2.116) |
IPM | 1.000 | 0.455 (ND) | |
FEP | 8.000 | ≥9.100 (ND) | |
CAZ | 1.000 | 8.756 (3.997–19.180) | |
P. aeruginosa MB3286 | MK-826 | 8.000 | 3.000 (1.060–8.470) |
IPM | 2.000 | 0.142 (0.059–0.341) | |
FEP | 2.000 | 0.422 (0.170–1.010) | |
CAZ | 2.000 | 0.394 (0.151–1.030) | |
P. mirabilis MB3125 | MK-826 | 0.031 | 0.034 (0.020–0.060) |
IPM | 4.000 | 12.200 (6.980–21.200) | |
FEP | 0.031 | 0.071 (ND) | |
CTRX | 0.031 | ≤0.004 (ND) | |
S. marcescens MB3548 | MK-826 | 0.500 | 0.121 (0.061–0.238) |
IPM | 1.000 | 4.720 (2.150–10.340) | |
FEP | 0.500 | 0.535 (0.271–1.054) | |
CTRX | 0.500 | 0.469 (0.270–0.817) |
MIC determined by procedures recommended by the National Committee for Clinical Laboratory Standards (14).
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.
Challenge with test organisms (0.5 ml; i.p.) and treatment (0.5 ml; s.c.) begun immediately and 4 h after infection (total of 2 doses).