The untreated and antibiotic-treated mice exhibited a 6–10 fold increase in spleen weights compared to healthy, uninfected animals. Bacterial loads in spleens were significantly reduced Topoisomerase inhibitor in antibiotic treated animals compared to untreated control but remained in the range of 1.6 × 104 CFU/g of spleen. The antibiotics administrated 24 hours post-infection for 10 days led to the development of a chronic, non-lethal abscess infection suggesting that B. mallei may have the propensity for latency, as does the very closely related organism

B. pseudomallei [25]. Efficacy of other antibiotics tested in hamsters revealed that time of administration of antimicrobials is the important factor affecting protection against B. mallei [24]. The experiments showed that administration of treatment less than 24 h post-exposure resulted in protection against the pathogen. A similar conclusion was obtained in antibiotics efficacy testing against B. pseudomallei infected mice [26]. Combined, this suggests that the infection could be contained or eliminated if very early antibiotic treatment was initiated to prevent the bacterial load from reaching EPZ015938 datasheet a lethal dose in the host. The pharmacokinetics

of each antimicrobial, relative to the in vitro MIC and the ability of the bacteria to reside in privileged intracellular sites (not always easily accessible to the antimicrobials) should be considered as an important factor in effective treatment. For that reason, we tested levofloxacin in our study since fluoroquinolones are known to penetrate renal,

lung and bronchial track tissues achieving a high intracellular concentration exceeding levels of the drug in serum [23]. Both antimicrobials were very effective in intracellular bacterial killing reducing bacterial loads to practically undetectable levels, validating Mirabegron their ability as cell-permeable antibiotics. Conclusion The current study showed that both ceftazidime and levofloxacin, despite good activity in vitro against B. mallei, failed to eradicate bacterium and resulted in development of a chronic, non-lethal form of glanders. Both antibiotics demonstrated some utility for treatment of glanders, including the ability for intracellular penetration and clearance of organisms in vitro, despite bacterial burdens recovered in vivo following i.p. antibiotic treatment. Methods Bacterial strain B. mallei strain ATCC 23344 (China 7) was cultured on Luria-Bertani supplemented with 4% glycerol (LBG) agar plates for 48 h at 37°C. Isolated colonies were sub-cultured to LBG broth, and cultures were incubated at 37°C until optical density readings at 600 nm (OD600) reached an exponential phase of Foretinib mouse growth. Bacteria were pelleted by centrifugation, washed and re-suspended in sterile 1× phosphate-buffered saline (PBS, pH 7.4) to obtain the desired CFU/ml. All procedures were performed in a biosafety level 3 laboratory.