Intravenous Doxycycline, Azithromycin, or Both for Severe Scrub Typhus
Issued Date
2023-01-01
Resource Type
ISSN
00284793
eISSN
15334406
Scopus ID
2-s2.0-85149427966
Pubmed ID
36856615
Journal Title
New England Journal of Medicine
Volume
388
Issue
9
Start Page
792
End Page
803
Rights Holder(s)
SCOPUS
Bibliographic Citation
New England Journal of Medicine Vol.388 No.9 (2023) , 792-803
Suggested Citation
Varghese G.M., Dayanand D., Gunasekaran K., Kundu D., Wyawahare M., Sharma N., Chaudhry D., Mahajan S.K., Saravu K., Aruldhas B.W., Mathew B.S., Nair R.G., Newbigging N., Mathew A., Abhilash K.P.P., Biswal M., Prasad A.H., Zachariah A., Iyadurai R., Hansdak S.G., Sathyendra S., Sudarsanam T.D., Prakash J.A.J., Manesh A., Mohan A., Tarning J., Blacksell S.D., Peerawaranun P., Waithira N., Mukaka M., Cheah P.Y., Peter J.V., Abraham O.C., Day N.P.J. Intravenous Doxycycline, Azithromycin, or Both for Severe Scrub Typhus. New England Journal of Medicine Vol.388 No.9 (2023) , 792-803. 803. doi:10.1056/NEJMoa2208449 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/82569
Title
Intravenous Doxycycline, Azithromycin, or Both for Severe Scrub Typhus
Author(s)
Varghese G.M.
Dayanand D.
Gunasekaran K.
Kundu D.
Wyawahare M.
Sharma N.
Chaudhry D.
Mahajan S.K.
Saravu K.
Aruldhas B.W.
Mathew B.S.
Nair R.G.
Newbigging N.
Mathew A.
Abhilash K.P.P.
Biswal M.
Prasad A.H.
Zachariah A.
Iyadurai R.
Hansdak S.G.
Sathyendra S.
Sudarsanam T.D.
Prakash J.A.J.
Manesh A.
Mohan A.
Tarning J.
Blacksell S.D.
Peerawaranun P.
Waithira N.
Mukaka M.
Cheah P.Y.
Peter J.V.
Abraham O.C.
Day N.P.J.
Dayanand D.
Gunasekaran K.
Kundu D.
Wyawahare M.
Sharma N.
Chaudhry D.
Mahajan S.K.
Saravu K.
Aruldhas B.W.
Mathew B.S.
Nair R.G.
Newbigging N.
Mathew A.
Abhilash K.P.P.
Biswal M.
Prasad A.H.
Zachariah A.
Iyadurai R.
Hansdak S.G.
Sathyendra S.
Sudarsanam T.D.
Prakash J.A.J.
Manesh A.
Mohan A.
Tarning J.
Blacksell S.D.
Peerawaranun P.
Waithira N.
Mukaka M.
Cheah P.Y.
Peter J.V.
Abraham O.C.
Day N.P.J.
Author's Affiliation
Mahidol Oxford Tropical Medicine Research Unit
Sri Venkateswara Institute of Medical Sciences
Pt. B.D. Sharma PGIMS, Rohtak
Indira Gandhi Medical College
Kasturba Medical College, Manipal
Nuffield Department of Medicine
Jawaharlal Institute of Postgraduate Medical Education and Research
Christian Medical College, Vellore
Postgraduate Institute of Medical Education & Research, Chandigarh
Sri Venkateswara Institute of Medical Sciences
Pt. B.D. Sharma PGIMS, Rohtak
Indira Gandhi Medical College
Kasturba Medical College, Manipal
Nuffield Department of Medicine
Jawaharlal Institute of Postgraduate Medical Education and Research
Christian Medical College, Vellore
Postgraduate Institute of Medical Education & Research, Chandigarh
Other Contributor(s)
Abstract
Background: The appropriate antibiotic treatment for severe scrub typhus, a neglected but widespread reemerging zoonotic infection, is unclear. Methods: In this multicenter, double-blind, randomized, controlled trial, we compared the efficacy of intravenous doxycycline, azithromycin, or a combination of both in treating severe scrub typhus. Patients who were 15 years of age or older with severe scrub typhus with at least one organ involvement were enrolled. The patients were assigned to receive a 7-day course of intravenous doxycycline, azithromycin, or both (combination therapy). The primary outcome was a composite of death from any cause at day 28, persistent complications at day 7, and persistent fever at day 5. Results: Among 794 patients (median age, 48 years) who were included in the modified intention-to-treat analysis, complications included those that were respiratory (in 62%), hepatic (in 54%), cardiovascular (in 42%), renal (in 30%), and neurologic (in 20%). The use of combination therapy resulted in a lower incidence of the composite primary outcome than the use of doxycycline (33% and 47%, respectively), for a risk difference of -13.3 percentage points (95% confidence interval [CI], -21.6 to -5.1; P=0.002). The incidence with combination therapy was also lower than that with azithromycin (48%), for a risk difference of -14.8 percentage points (95% CI, -23.1 to -6.5; P<0.001). No significant difference was seen between the azithromycin and doxycycline groups (risk difference, 1.5 percentage points; 95% CI, -7.0 to 10.0; P=0.73). The results in the per-protocol analysis were similar to those in the primary analysis. Adverse events and 28-day mortality were similar in the three groups. Conclusions: Combination therapy with intravenous doxycycline and azithromycin was a better therapeutic option for the treatment of severe scrub typhus than monotherapy with either drug alone.