Published online Dec 31, 2008.
https://doi.org/10.3947/ic.2008.40.6.311
In vitro Efficacy of Antibiotic Combinations against Orientia tsutsugamushi
Abstract
Background
Occasionally, combinations of antibiotics are used for the treatment of scrub typhus. However, the effectiveness of such combined therapies has rarely been evaluated. To date, no experimental studies have been performed; only 1 clinical study has assessed the efficacy of combined doxycycline and rifampin therapy. To elucidate the efficacies of other antibiotic combinations, we performed an experiment to evaluate the in vitro efficacy of antibiotic combinations against Orientia tsutsugamushi.
Materials and Methods
O. tsutsugamushi strain Boryong was inoculated into the ECV304 cell line. The infected cells were cultured in antibiotic-containing media for 3-5 days and stained with FS15, a monoclonal antibody reacting against the linear epitope on the 56-kDa major outer membrane protein of O. tsutsugamushi. Thereafter, antimicrobial susceptibility was measured by flow cytometry and expressed as a growth index (total mass of Orientia). The growth indices of doxycycline (0.1 µg/mL), azithromycin (0.1 µg/mL), rifampin (0.0125 µg/mL), cefotaxime (2 and 20 µg/mL), and their various combinations (doxycycline+cefotaxime, doxycycline+rifampin, azithromycin+cefotaxime, and rifampin+cefotaxime) were measured. The above mentioned antibiotic concentrations, except for that of cefotaxime, represent the minimal inhibitory concentrations of each antibiotic.
Results
The growth indices of doxycycline (4.67% and 0.52%), rifampin (2.35% and 0.26%), and azithromycin (7.54%) were within the range of full suppression of O. tsutsugamushi; in contrast, cefotaxime (87.60%) was in effective. The growth indices of doxycycline+rifampin were 0.10% and 0.10%, which were similar to those obtained with doxycycline or rifampin alone. The growth indices of doxycycline+cefotaxime were 3.99% and 3.65% in low-dose cefotaxime (2 µg/mL), and 3.69% and 4.40% in high-dose cefotaxime (20 µg/mL). The growth indices of rifampin+cefotaxime (2.19% and 2.19% at 2 µg/mL; 1.84% and 2.04% at 20 µg/mL cefotaxime) were similar to those obtained with rifampin alone (2.35% and 0.26%). Azithromycin+cefotaxime (11.06-14.63%) showed higher growth indices than azithromycin alone; this suggests that this combination may be antagonistic.
Conclusions
The anti-Orientia efficacies of doxycycline+rifampin, doxycycline+cefotaxime, and rifampin+cefotaxime were not antagonistic. The efficacy of the azithromycin+cefotaxime combination needs to be confirmed by more sensitive methods to exclude the possibility of antagonistic interactions between the antibiotics.
Table
Comparison of Growth Indices (%) between Doxycycline, Azithromycin, Rifampin, and Cefotaxime Alone and Combination of These Antibiotics
References
-
Kim YS, Choi SY, Lee MS, Cheung DR, Kim EO, Woo JH, Ryu JS. Clinical and molecular biological investigation of therapeutic modalities and treatment duration of tsutsugamushi disease (scrub typhus). J Korean Soc Chemother 1999;17:385–393.
-
-
Chung MH, Han SW, Choi MG, Chang WH, Pai HJ, Shin HS, Jung HJ, Kang MH, Jung JY. Comparison of a 3-day course of azithromycin with doxycycline for the treatment of scrub typhus. Korean J Infect Dis 2000;32:433–438.
-
-
Kim ES, Kim MK, Lee HM, Chung MH, Lee JS, Park JE, Kang JS. In vitro antibiotic susceptibility of Orientia tsutsugamushi strain Boryong measured by flow cytometry. Infect Chemother 2008;40:212–217.
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-
Park SD, Chung MH, Lee HM, Kim MK, Kang JS. A case of scrub typhus in summer presenting as atypical pneumonia. Infect Chemother 2008;40:241–245.
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