TABLE 1.
Evaluating the relationship between hypoxia and metronidazole activity in vitro and in vivo
| Model | Method to measure or demonstrate hypoxia | Evidence of hypoxia? | Caseating granulomas? | Activity of metronidazole | References |
|---|---|---|---|---|---|
| Wayne in vitro model of dormancy | <0.06% O2, methylene blue decolorization | Yes | No | Active | 19, 95 |
| Mouse: C57Bl/6 | Pimonidazole (immunohistochemistry), EF5/ELK3-51 antibody | No | No | Inactive | 13, 17, 294, 295 |
| Mouse: BALB/c | Copper(II)-diacetyl-bis(N4-methyl-thiosemicarbazone), pimonidazole (immunohistochemistry) | No | No | Inactive | 17, 64, 296, 297 |
| Mouse: C3HeB/FeJ “Kramnik model” | Copper(II)-diacetyl-bis(N4-methyl-thiosemicarbazone), pimonidazole (immunohistochemistry), gene expression of hypoxia-associated genes in M. tuberculosis | Yes | Yes | Inactive | 64, 296, 297 |
| Guinea pig | Pimonidazole (immunohistochemistry) | Yes | Yes | Inactive | 15, 17 |
| Rabbit | Pimonidazole (immunohistochemistry), fiber-optic O2 probe | Yes | Yes | Active | 17 |
| Non-human primates | Pimonidazole (immunohistochemistry) | Yes | Yes | Active | 16, 17 |
| Human | EF5/ELK3-51 antibody, HIF-1α (hypoxia inducible factor) (immunohistochemistry), [18F]-fluoromisonidazole (positron emission tomography imaging) | Yes | Yes | Clinically ineffective | 14, 245, 294, 298 |