Bactericidal activities of antibiotics against intracellular Francisella tularensis

Abstract

MICs of many antibiotics for Francisella tularensis are low in axenic medium, whereas only aminoglycosides, tetracyclines, and fluoroquinolones are useful in treating tularemic patients. In an in vitro cell system, only these antibiotics, rifampin, and telithromycin were bactericidal against intracellular F. tularensis. These results correlate better with clinical data than MIC data do.

FIG. 1

Activities of antibiotics against intracellular F. tularensis. (A) Penicillin G (10 μg/ml), amoxicillin (10 μg/ml), ceftriaxone (10 and 100 μg/ml), streptomycin (10 μg/ml), gentamicin (3 and 10 μg/ml), and amikacin (10 μg/ml). (B) Doxycycline (4 μg/ml), thiamphenicol (4 μg/ml), rifampin (4 μg/ml), trimethoprim-sulfamethoxazole (10 and 50 μg/ml, respectively), erythromycin (4 μg/ml), clarithromycin (4 μg/ml), telithromycin (4 μg/ml), ofloxacin (1 μg/ml), and ciprofloxacin (1 μg/ml). I/Io, ratio of the viable bacterial titers (CFU per milliliter), after 24, 48, or 72 h of incubation of cultures in the presence of the various antibiotics tested to the primary F. tularensis inoculation dose. Data correspond to a single experiment performed in triplicate. All data points with at least a 1-log decrease were statistically significantly different from controls (P < 0.001).