Comparative studies evaluating mouse models used for efficacy testing of experimental drugs against Mycobacterium tuberculosis.

Methodologies for preclinical animal model testing of drugs against Mycobacterium tuberculosis vary from laboratory to laboratory; however, it is unknown if these variations result in different outcomes. Thus, a series of head-to-head comparisons of drug regimens in three commonly used mouse models (intravenous, a low-dose aerosol, and a high-dose aerosol infection model) and in two strains of mice are reported here. Treatment with standard tuberculosis (TB) drugs resulted in similar efficacies in two mouse species after a low-dose aerosol infection. When comparing the three different infection models, the efficacies in mice of rifampin and pyrazinamide were similar when administered with either isoniazid or moxifloxacin. Relapse studies revealed that the standard drug regimen showed a significantly higher relapse rate than the moxifloxacin-containing regimen. In fact, 4 months of the moxifloxacin-containing combination regimen showed similar relapse rates as 6 months of the standard regimen. The intravenous model showed slower bactericidal killing kinetics with the combination regimens tested and a higher relapse of infection than either aerosol infection models. All three models showed similar outcomes for in vivo efficacy and relapse of infection for the drug combinations tested, regardless of the mouse infection model used. Efficacy data for the drug combinations used also showed similar results, regardless of the formulation used for rifampin or timing of the drugs administered in combination. In all three infection models, the dual combination of rifampin and pyrazinamide was less sterilizing than the standard three-drug regimen, and therefore the results do not support the previously reported antagonism between standard TB agents.

Efficacy of Erymicin 200 Injections for Reducing Renibacterium salmoninarum and Controlling Vertical Transmission in an Inland Rainbow Trout Brood Stock.

Bacterial Kidney Disease, caused by Renibacterium salmoninarum (Rs), is widespread and can cause significant mortality at most life stages in infected salmonids. Rs is commonly found in inland trout, which can be carriers of the bacterium. Lethal spawns can be used to control vertical transmission to progeny through the culling of eggs from infected parents, but can be costly, time-consuming, and can negatively impact important and rare brood stocks. Erymicin 200 is an Investigational New Animal Drug (INAD) intended to reduce Rs levels in hatchery brood stocks and control vertical transmission to progeny. We tested the efficacy of Erymicin 200 injections in a positive, hatchery-resident rainbow trout (Oncorhynchus mykiss) brood stock in Colorado, USA. Brood fish age two and three were injected with 25 mg per kg of body weight Erymicin 200 three times prior to spawning. Erymicin 200 was effective in reducing Rs to below detectable levels in treated fish. However, both negative treated and control brood fish produced positive progeny, suggesting that Erymicin 200 did not prevent the vertical transmission of Rs.