Comparison of the in vitro and in vivo susceptibilities of Burkholderia mallei to Ceftazidime and Levofloxacin.
BACKGROUND
Burkholderia mallei is a zoonotic Gram negative bacterium which primarily infects solipeds but can cause lethal disease in humans if left untreated. The effect of two antibiotics with different modes of action on Burkholderia mallei strain ATCC23344 was investigated by using in vitro and in vivo studies.


RESULTS
Determination of minimal inhibitory concentrations (MICs) in vitro was done by the agar diffusion method and the dilution method. The MICs of levofloxacin and ceftazidime were in the similar range, 2.5 and 5.0 microg/ml, respectively. Intracellular susceptibility of the bacterium to these two antibiotics in J774A.1 mouse macrophages in vitro was also investigated. Macrophages treated with antibiotics demonstrated uptake of the drugs and reduced bacterial loads in vitro. The efficacy of ceftazidime and levofloxacin were studied in BALB/c mice as post-exposure treatment following intranasal B. mallei infection. Intranasal infection with 5 x 10(5) CFUs of B. mallei resulted in 90% death in non-treated control mice. Antibiotic treatments 10 days post-infection proved to be effective in vivo with all antibiotic treated mice surviving to day 34 post-infection. The antibiotics did not result in complete clearance of the bacterial infection and presence of the bacteria was found in lungs and spleens of the survivors, although bacterial burden recovered from levofloxacin treated animals appeared reduced compared to ceftazidime.


CONCLUSIONS
Both antibiotics demonstrated utility for the treatment of glanders, including the ability for intracellular penetration and clearance of organisms in vitro.
Department of Pediatrics, University of Texas Medical Branch, Galveston, Texas, USA. bmjudy@utmb.edu
Barbara M
BM
Judy
Gregory C
GC
Whitlock
Alfredo G
AG
Torres
D Mark
DM
Estes
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D042726:Burkholderia mallei / Q000187:drug effects*; D002442:Ceftazidime / Q000494:pharmacology*; D002460:Cell Line; D024881:Drug Resistance, Bacterial; D005260:Female; D005896:Glanders / Q000188:drug therapy / Q000382:microbiology; D064704:Levofloxacin; D008264:Macrophages / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008826:Microbial Sensitivity Tests; D015242:Ofloxacin / Q000494:pharmacology*
D000900:Anti-Bacterial Agents; D064704:Levofloxacin; D002442:Ceftazidime; D015242:Ofloxacin