Investigate the appropriate antibiotic therapy for severe scrub typhus
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Reviewed by Dat Tien Nguyen, B.A, ScM.
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Posted on March 3rd, 2023
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Severe scrub typhus is an emerging zoonotic infection caused by the bacteria Orientia tsutsugamushi. The bacteria is spread by a mite that has been found in many regions in Southeast asia. Globally, there are approximately 1 million cases of severe scrub typhus which resulted in 150,000 deaths every year. Despite the great disease burden, there has not been any consensus about the most appropriate antibiotic. Thus, a study funded by the Wellcome Trust was conducted to compare the effectiveness of doxycycline, azithromycin, or both in treating severe scrub typhus.
The randomized controlled trial was conducted in India and included 794 patients who were at least 15 years old (median age = 46 years old) and have been diagnosed with severe scrub typhus and experienced complications to at least 1 organ system. These patients were equally divided into 3 treatment groups that were continued for 7 days. Those in the doxycycline monotherapy group were given an intravenous infusion of 200 mg doxycycline twice a day on the 1st day, and 100 mg twice a day for the rest of the study period. Those in the azithromycin monotherapy group were given an IV infusion of 500 mg of azithromycin twice a day for the 1st day, and 500 mg once a day for the next 6 days. The last group was given a combination of doxycycline and azithromycin at the dosage written above. The effectiveness of the treatment was determined based on the absence of the following criteria: 1) mortality occurs after 28 days; 2) complication persists after 1 week; 3) fever happens after 5 days. The study concluded that the combination therapy of doxycycline and azithromycin was 13% more effective than the doxycycline monotherapy and 15% more effective than the azithromycin monotherapy at treating severe scrub typhus. There was no significant difference between those who were treated with only doxycycline and azithromycin. Since azithromycin inhibits the bacterial 50s ribosomal subunit and doxycycline targets the 30s ribosomal subunit, combining these two antibiotics might have completely interfered with bacterial protein synthesis mechanism. There was little difference in adverse events between the 3 treatment groups, and the average rate of treatment discontinuation was approximately 5%.
The randomized controlled trial was conducted in India and included 794 patients who were at least 15 years old (median age = 46 years old) and have been diagnosed with severe scrub typhus and experienced complications to at least 1 organ system. These patients were equally divided into 3 treatment groups that were continued for 7 days. Those in the doxycycline monotherapy group were given an intravenous infusion of 200 mg doxycycline twice a day on the 1st day, and 100 mg twice a day for the rest of the study period. Those in the azithromycin monotherapy group were given an IV infusion of 500 mg of azithromycin twice a day for the 1st day, and 500 mg once a day for the next 6 days. The last group was given a combination of doxycycline and azithromycin at the dosage written above. The effectiveness of the treatment was determined based on the absence of the following criteria: 1) mortality occurs after 28 days; 2) complication persists after 1 week; 3) fever happens after 5 days. The study concluded that the combination therapy of doxycycline and azithromycin was 13% more effective than the doxycycline monotherapy and 15% more effective than the azithromycin monotherapy at treating severe scrub typhus. There was no significant difference between those who were treated with only doxycycline and azithromycin. Since azithromycin inhibits the bacterial 50s ribosomal subunit and doxycycline targets the 30s ribosomal subunit, combining these two antibiotics might have completely interfered with bacterial protein synthesis mechanism. There was little difference in adverse events between the 3 treatment groups, and the average rate of treatment discontinuation was approximately 5%.