In vitro Synergism between Chloroquine and Antibiotics against Orientia tsutsugamushi
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Background: To investigate whether chloroquine enhances the effect of antibiotics against Orientia tsutsugamushi, the causativeorganism of scrub typhus, we compared the effect of antibiotics in combination with chloroquine with the effect of antibioticsalone in vitro. Materials and Methods: The Boryong or AFSC-4 strain was inoculated into ECV304 cells, and incubated in medium containingdoxycycline (4 μg/mL), rifampin (4 μg/mL), azithromycin (0.5 μg/mL), chloroquine (1 μg/mL), and each of these antibiotics incombination with chloroquine for 7 d. Immunofluorescence (IF) staining for O. tsutsugamushi was performed 4 hr and 7 d afterinoculation of the bacteria, and IF-positive foci were enumerated. Results: Chloroquine inhibited the growth of O. tsutsugamushi by 15.5%. In combination with chloroquine, the antimicrobialeffects increased by 4.4% for doxycycline (a 92.9% reduction of bacterial numbers for doxycycline versus a 97.3% reductionfor doxycycline plus chloroquine), 4.6% for rifampin (90.0% versus 94.6%), and 8.3% for azithromycin (86.9% versus 95.2%). The antimicrobial effect of the antibiotics alone was significantly different compared to the combined effect of antibiotics andchloroquine (Wilcoxon signed-rank test, P = 0.001). Conclusions: The combined use of chloroquine with an antibiotic for the treatment of O. tsutsugamushi infections may be usefulfor increasing the efficacy of the antibiotics.
Abstract
Background: To investigate whether chloroquine enhances the effect of antibiotics against Orientia tsutsugamushi, the causativeorganism of scrub typhus, we compared the effect of antibiotics in combination with chloroquine with the effect of antibioticsalone in vitro. Materials and Methods: The Boryong or AFSC-4 strain was inoculated into ECV304 cells, and incubated in medium containingdoxycycline (4 μg/mL), rifampin (4 μg/mL), azithromycin (0.5 μg/mL), chloroquine (1 μg/mL), and each of these antibiotics incombination with chloroquine for 7 d. Immunofluorescence (IF) staining for O. tsutsugamushi was performed 4 hr and 7 d afterinoculation of the bacteria, and IF-positive foci were enumerated. Results: Chloroquine inhibited the growth of O. tsutsugamushi by 15.5%. In combination with chloroquine, the antimicrobialeffects increased by 4.4% for doxycycline (a 92.9% reduction of bacterial numbers for doxycycline versus a 97.3% reductionfor doxycycline plus chloroquine), 4.6% for rifampin (90.0% versus 94.6%), and 8.3% for azithromycin (86.9% versus 95.2%). The antimicrobial effect of the antibiotics alone was significantly different compared to the combined effect of antibiotics andchloroquine (Wilcoxon signed-rank test, P = 0.001). Conclusions: The combined use of chloroquine with an antibiotic for the treatment of O. tsutsugamushi infections may be usefulfor increasing the efficacy of the antibiotics.
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