mallei. There is a need for an extensive evaluation of susceptibility of antibiotics to these pathogens beyond in vitro studies. Animal models to study equine glanders have been established [18] while there is a general lack of infection models that mimic human infection. Among rodents, guinea pigs and hamsters are most susceptible to glanders [19]. Mice, on the other hand, have similar resistance to glanders infections as humans, which makes this model more SP600125 suitable to study therapies for B. mallei.

Only intraperitoneal pathogenesis of glanders has been well described in the mouse model [20] with more recent studies of the bacterium administered via the aerosol or intranasal routes [21]. Here, we evaluated the susceptibilities in vitro of GW-572016 cost B. mallei to ceftazidime and levofloxacin, and their efficacy in vivo using intranasal infection in BALB/c mice, as inhalation would be the most likely route of infection in the event of bioterrorism threat. In previous in vitro studies, ceftazidime proved to be effective against B. mallei among others including imipenem, doxycycline, piperacillin, ciprofloxacin

[8, 9]. Levofloxacin demonstrates relatively high levels of activity against B. mallei but not B. pseudomallei GSK126 nmr [22]. Levofloxacin is known to achieve higher intracellular concentration and is recommended for intracellular infections [23]. Our results indicate that B. mallei strain ATCC 23344 is susceptible to a concentration as low as 2.5 μg/ml of levofloxacin and 5 μg/ml of ceftazidime. These results confirmed prior studies evaluating susceptibility of 15 isolates of B. mallei

to 35 antimicrobial agents [15]. In this study, ceftazidime and levofloxacin appeared in the group of most effective drugs tested in this panel against B. mallei. However, the high percentage of resistant strains of B. pseudomallei to levofloxacin and the emergence of ceftazidime-resistant clinical isolates of Cobimetinib molecular weight B. pseudomallei would affect the recommendations of these drugs as useful treatment for both glanders and melioidosis, underlining the need for supplementary monitoring of the effectiveness of the recommended antimicrobials. The effectiveness of levofloxacin and ceftazidime in vitro were substantiated in our in vivo experiments with all treated mice surviving at least 34 days post infection. The intranasal infection of mice with 5 × 105 CFUs of B. mallei resulted in 90% death in untreated control mice. Treatment with antibiotics used in this study prevented the development of an acute lethal form of disease but lacked the ability to provide complete clearance of the bacterial infection. By 34 days post-infection, bacteria were largely cleared from the lungs with no significant differences between treatments. Interestingly, in our intranasal infection model, the spleen appears to be the major target tissue for glanders infection and a site of multifocal abscesses.