ArticleAntibiotics (Basel, Switzerland)2026
Plasma and Intracellular Concentrations of Doxycycline and Azithromycin in Patients with Severe Scrub Typhus.
Article in Antibiotics (Basel, Switzerland), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
BACKGROUND/
objectivesScrub typhus, a life-threatening infection caused by
methodsA randomly selected subset of adult (>18 years) participants from the INTREST trial (Clinical Trials Registry-India, number CTRI/2018/08/015159), who had been randomized in a 1:1:1 ratio to receive doxycycline, azithromycin, or both drugs, respectively, were included in this study for comparative drug concentration analysis. Blood samples were collected on days 0, 1, 3, and 7 to monitor bacterial load using quantitative polymerase chain reaction (PCR). Five milliliters of sterile blood were collected 3-10 h after the final dose on day 7 for comparative drug concentration measured using high-resolution multiple reaction monitoring. Data were analyzed in GraphPad Prism v.10.0.3.
resultsFifty-one patients (males, 59%; median age, 52 years) were enrolled. Fifteen, seventeen, and nineteen patients received azithromycin, doxycycline, and both, respectively. Doxycycline achieved a median plasma concentration of 1112 (42.51-5697) ng/mL and was undetectable intracellularly. The intracellular concentration of azithromycin (1127 [16.78-19,250] ng/mL) surpassed its plasma concentration (227.1 [48.78-1022] ng/mL). On day 3, PCR negativity rates were 56.24%, 93.3%, and 94.7% in the doxycycline, azithromycin, and combination groups, respectively.
conclusionsThe high plasma concentrations of doxycycline and intracellular accumulation of azithromycin may contribute to improved clinical outcomes when used in combination.
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