In vitro Antagonism between Cefotaxime and Anti-Rickettsial Antibiotics against Orientia tsutsugamushi

We have investigated the in vitro antimicrobial effects of antibiotic combinations against Orientia tsutsugamushi, the causative agent of scrub typhus. ECV304 cells were infected with the Boryong strain of O. tsutsugamushi and incubated in a medium containing doxycycline (4 µg/mL), azithromycin (0.5 µg/mL), rifampin (4 µg/mL), ciprofloxacin (25 µg/mL), gentamicin (5 µg/mL), cefotaxime (2 µg/mL), or combinations of these agents for 7 days, after which immunofluorescent staining for O. tsutsugamushi was performed. The percentages of infective foci in cultures containing antibiotics compared to those in cultures without antibiotics were 6.2% for doxycycline, 9.6% for azithromycin, 8.8% for rifampin, 96.6% for cefotaxime, 29.7% for doxycycline plus cefotaxime, 23.6% for azithromycin plus cefotaxime, and 41.4% for rifampin plus cefotaxime. These findings show an in vitro antagonism between anti-rickettsial agents and cefotaxime against O. tsutsugamushi. These results suggest that the efficacy of antibiotic combinations involving cefotaxime for the treatment of patients with scrub typhus, particularly those with severe pneumonia, needs to be investigated.