EFFICACY OF ANTIBIOTICS AGAINST EXTRACELLULAR AND INTRACELLULAR BURKHOLDERIA PSEUDOMALLEI, AND THEIR THERAPEUTIC EFFECTS ON EXPERIMENTAL PEUMONIA IN MICE

We examined the effects of 14 antibiotics on the isolated strains of B. pseudomallei from melioidosis patients in Thailand. The organisms caused pneumonia and was found to survive in macrophages in mice. Thirteen strains of B. pseudomallei isolates showed resistance to avariety of antibiotics such as ampicillin, cefazolin, cefotiam, gentamycin, erthromycin, and clindamycin. Piperacillin, ceftazidime, ceftizoxime, minocycline, ciprofloxacin, levofloxacin and ofloxacin were moderately active antibiotics. Imipenem was the most active antibiotic. Efficacy of imipenem and levofloxacin were also examined against the organism in the macrophage. Imipenem showed the strong MIC, (MIC=0.125 mg/L), but a 4×MIC dose did not inhibit intracellular growth of the organism in mice peritoneal macrophages. In contrast, a 4×MIC of levofloxacin inhibited the intracellular growth although the MIC=1mg/L. Levofloxacin therapy showed a significantly (P <0.01 or P <0.05) higher survival rate than imipenem/cilastatin, piperacillin and minocycline against experimental B. pseudomallei pneumonia in mice. Imipenem/cilastatin and ceftazidime showed almost the same effectivity against the infection, although imipenem/cilastatin required half the dosage of ceftazidime.Levofloxacin may be the first choice in the treatment of melioidosis caused by B. pseudomallei.