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Intravenous Doxycycline, Azithromycin, or Both for Severe Scrub Typhus.
Varghese, George M; Dayanand, Divya; Gunasekaran, Karthik; Kundu, Debasree; Wyawahare, Mukta; Sharma, Navneet; Chaudhry, Dhruva; Mahajan, Sanjay K; Saravu, Kavitha; Aruldhas, Blessed W; Mathew, Binu S; Nair, Roshini G; Newbigging, Nalini; Mathew, Aswathy; Abhilash, Kundavaram P P; Biswal, Manisha; Prasad, Ann H; Zachariah, Anand; Iyadurai, Ramya; Hansdak, Samuel G; Sathyendra, Sowmya; Sudarsanam, Thambu D; Prakash, John A J; Manesh, Abi; Mohan, Alladi; Tarning, Joel; Blacksell, Stuart D; Peerawaranun, Pimnara; Waithira, Naomi; Mukaka, Mavuto; Cheah, Phaik Yeong; Peter, John V; Abraham, Ooriapadickal C; Day, Nicholas P J.
Affiliation
  • Varghese GM; From the Departments of Infectious Diseases (G.M.V., D.D., D.K., R.G.N., A.H.P., A. Manesh), Medicine (K.G., N.N., A.Z., R.I., S.G.H., S.S., T.D.S., O.C.A.), Pharmacology (B.W.A., B.S.M., A. Mathew), Emergency Medicine (K.P.P.A.), Microbiology (J.A.J.P.), and Critical Care (J.V.P.), Christian Medica
  • Dayanand D; From the Departments of Infectious Diseases (G.M.V., D.D., D.K., R.G.N., A.H.P., A. Manesh), Medicine (K.G., N.N., A.Z., R.I., S.G.H., S.S., T.D.S., O.C.A.), Pharmacology (B.W.A., B.S.M., A. Mathew), Emergency Medicine (K.P.P.A.), Microbiology (J.A.J.P.), and Critical Care (J.V.P.), Christian Medica
  • Gunasekaran K; From the Departments of Infectious Diseases (G.M.V., D.D., D.K., R.G.N., A.H.P., A. Manesh), Medicine (K.G., N.N., A.Z., R.I., S.G.H., S.S., T.D.S., O.C.A.), Pharmacology (B.W.A., B.S.M., A. Mathew), Emergency Medicine (K.P.P.A.), Microbiology (J.A.J.P.), and Critical Care (J.V.P.), Christian Medica
  • Kundu D; From the Departments of Infectious Diseases (G.M.V., D.D., D.K., R.G.N., A.H.P., A. Manesh), Medicine (K.G., N.N., A.Z., R.I., S.G.H., S.S., T.D.S., O.C.A.), Pharmacology (B.W.A., B.S.M., A. Mathew), Emergency Medicine (K.P.P.A.), Microbiology (J.A.J.P.), and Critical Care (J.V.P.), Christian Medica
  • Wyawahare M; From the Departments of Infectious Diseases (G.M.V., D.D., D.K., R.G.N., A.H.P., A. Manesh), Medicine (K.G., N.N., A.Z., R.I., S.G.H., S.S., T.D.S., O.C.A.), Pharmacology (B.W.A., B.S.M., A. Mathew), Emergency Medicine (K.P.P.A.), Microbiology (J.A.J.P.), and Critical Care (J.V.P.), Christian Medica
  • Sharma N; From the Departments of Infectious Diseases (G.M.V., D.D., D.K., R.G.N., A.H.P., A. Manesh), Medicine (K.G., N.N., A.Z., R.I., S.G.H., S.S., T.D.S., O.C.A.), Pharmacology (B.W.A., B.S.M., A. Mathew), Emergency Medicine (K.P.P.A.), Microbiology (J.A.J.P.), and Critical Care (J.V.P.), Christian Medica
  • Chaudhry D; From the Departments of Infectious Diseases (G.M.V., D.D., D.K., R.G.N., A.H.P., A. Manesh), Medicine (K.G., N.N., A.Z., R.I., S.G.H., S.S., T.D.S., O.C.A.), Pharmacology (B.W.A., B.S.M., A. Mathew), Emergency Medicine (K.P.P.A.), Microbiology (J.A.J.P.), and Critical Care (J.V.P.), Christian Medica
  • Mahajan SK; From the Departments of Infectious Diseases (G.M.V., D.D., D.K., R.G.N., A.H.P., A. Manesh), Medicine (K.G., N.N., A.Z., R.I., S.G.H., S.S., T.D.S., O.C.A.), Pharmacology (B.W.A., B.S.M., A. Mathew), Emergency Medicine (K.P.P.A.), Microbiology (J.A.J.P.), and Critical Care (J.V.P.), Christian Medica
  • Saravu K; From the Departments of Infectious Diseases (G.M.V., D.D., D.K., R.G.N., A.H.P., A. Manesh), Medicine (K.G., N.N., A.Z., R.I., S.G.H., S.S., T.D.S., O.C.A.), Pharmacology (B.W.A., B.S.M., A. Mathew), Emergency Medicine (K.P.P.A.), Microbiology (J.A.J.P.), and Critical Care (J.V.P.), Christian Medica
  • Aruldhas BW; From the Departments of Infectious Diseases (G.M.V., D.D., D.K., R.G.N., A.H.P., A. Manesh), Medicine (K.G., N.N., A.Z., R.I., S.G.H., S.S., T.D.S., O.C.A.), Pharmacology (B.W.A., B.S.M., A. Mathew), Emergency Medicine (K.P.P.A.), Microbiology (J.A.J.P.), and Critical Care (J.V.P.), Christian Medica
  • Mathew BS; From the Departments of Infectious Diseases (G.M.V., D.D., D.K., R.G.N., A.H.P., A. Manesh), Medicine (K.G., N.N., A.Z., R.I., S.G.H., S.S., T.D.S., O.C.A.), Pharmacology (B.W.A., B.S.M., A. Mathew), Emergency Medicine (K.P.P.A.), Microbiology (J.A.J.P.), and Critical Care (J.V.P.), Christian Medica
  • Nair RG; From the Departments of Infectious Diseases (G.M.V., D.D., D.K., R.G.N., A.H.P., A. Manesh), Medicine (K.G., N.N., A.Z., R.I., S.G.H., S.S., T.D.S., O.C.A.), Pharmacology (B.W.A., B.S.M., A. Mathew), Emergency Medicine (K.P.P.A.), Microbiology (J.A.J.P.), and Critical Care (J.V.P.), Christian Medica
  • Newbigging N; From the Departments of Infectious Diseases (G.M.V., D.D., D.K., R.G.N., A.H.P., A. Manesh), Medicine (K.G., N.N., A.Z., R.I., S.G.H., S.S., T.D.S., O.C.A.), Pharmacology (B.W.A., B.S.M., A. Mathew), Emergency Medicine (K.P.P.A.), Microbiology (J.A.J.P.), and Critical Care (J.V.P.), Christian Medica
  • Mathew A; From the Departments of Infectious Diseases (G.M.V., D.D., D.K., R.G.N., A.H.P., A. Manesh), Medicine (K.G., N.N., A.Z., R.I., S.G.H., S.S., T.D.S., O.C.A.), Pharmacology (B.W.A., B.S.M., A. Mathew), Emergency Medicine (K.P.P.A.), Microbiology (J.A.J.P.), and Critical Care (J.V.P.), Christian Medica
  • Abhilash KPP; From the Departments of Infectious Diseases (G.M.V., D.D., D.K., R.G.N., A.H.P., A. Manesh), Medicine (K.G., N.N., A.Z., R.I., S.G.H., S.S., T.D.S., O.C.A.), Pharmacology (B.W.A., B.S.M., A. Mathew), Emergency Medicine (K.P.P.A.), Microbiology (J.A.J.P.), and Critical Care (J.V.P.), Christian Medica
  • Biswal M; From the Departments of Infectious Diseases (G.M.V., D.D., D.K., R.G.N., A.H.P., A. Manesh), Medicine (K.G., N.N., A.Z., R.I., S.G.H., S.S., T.D.S., O.C.A.), Pharmacology (B.W.A., B.S.M., A. Mathew), Emergency Medicine (K.P.P.A.), Microbiology (J.A.J.P.), and Critical Care (J.V.P.), Christian Medica
  • Prasad AH; From the Departments of Infectious Diseases (G.M.V., D.D., D.K., R.G.N., A.H.P., A. Manesh), Medicine (K.G., N.N., A.Z., R.I., S.G.H., S.S., T.D.S., O.C.A.), Pharmacology (B.W.A., B.S.M., A. Mathew), Emergency Medicine (K.P.P.A.), Microbiology (J.A.J.P.), and Critical Care (J.V.P.), Christian Medica
  • Zachariah A; From the Departments of Infectious Diseases (G.M.V., D.D., D.K., R.G.N., A.H.P., A. Manesh), Medicine (K.G., N.N., A.Z., R.I., S.G.H., S.S., T.D.S., O.C.A.), Pharmacology (B.W.A., B.S.M., A. Mathew), Emergency Medicine (K.P.P.A.), Microbiology (J.A.J.P.), and Critical Care (J.V.P.), Christian Medica
  • Iyadurai R; From the Departments of Infectious Diseases (G.M.V., D.D., D.K., R.G.N., A.H.P., A. Manesh), Medicine (K.G., N.N., A.Z., R.I., S.G.H., S.S., T.D.S., O.C.A.), Pharmacology (B.W.A., B.S.M., A. Mathew), Emergency Medicine (K.P.P.A.), Microbiology (J.A.J.P.), and Critical Care (J.V.P.), Christian Medica
  • Hansdak SG; From the Departments of Infectious Diseases (G.M.V., D.D., D.K., R.G.N., A.H.P., A. Manesh), Medicine (K.G., N.N., A.Z., R.I., S.G.H., S.S., T.D.S., O.C.A.), Pharmacology (B.W.A., B.S.M., A. Mathew), Emergency Medicine (K.P.P.A.), Microbiology (J.A.J.P.), and Critical Care (J.V.P.), Christian Medica
  • Sathyendra S; From the Departments of Infectious Diseases (G.M.V., D.D., D.K., R.G.N., A.H.P., A. Manesh), Medicine (K.G., N.N., A.Z., R.I., S.G.H., S.S., T.D.S., O.C.A.), Pharmacology (B.W.A., B.S.M., A. Mathew), Emergency Medicine (K.P.P.A.), Microbiology (J.A.J.P.), and Critical Care (J.V.P.), Christian Medica
  • Sudarsanam TD; From the Departments of Infectious Diseases (G.M.V., D.D., D.K., R.G.N., A.H.P., A. Manesh), Medicine (K.G., N.N., A.Z., R.I., S.G.H., S.S., T.D.S., O.C.A.), Pharmacology (B.W.A., B.S.M., A. Mathew), Emergency Medicine (K.P.P.A.), Microbiology (J.A.J.P.), and Critical Care (J.V.P.), Christian Medica
  • Prakash JAJ; From the Departments of Infectious Diseases (G.M.V., D.D., D.K., R.G.N., A.H.P., A. Manesh), Medicine (K.G., N.N., A.Z., R.I., S.G.H., S.S., T.D.S., O.C.A.), Pharmacology (B.W.A., B.S.M., A. Mathew), Emergency Medicine (K.P.P.A.), Microbiology (J.A.J.P.), and Critical Care (J.V.P.), Christian Medica
  • Manesh A; From the Departments of Infectious Diseases (G.M.V., D.D., D.K., R.G.N., A.H.P., A. Manesh), Medicine (K.G., N.N., A.Z., R.I., S.G.H., S.S., T.D.S., O.C.A.), Pharmacology (B.W.A., B.S.M., A. Mathew), Emergency Medicine (K.P.P.A.), Microbiology (J.A.J.P.), and Critical Care (J.V.P.), Christian Medica
  • Mohan A; From the Departments of Infectious Diseases (G.M.V., D.D., D.K., R.G.N., A.H.P., A. Manesh), Medicine (K.G., N.N., A.Z., R.I., S.G.H., S.S., T.D.S., O.C.A.), Pharmacology (B.W.A., B.S.M., A. Mathew), Emergency Medicine (K.P.P.A.), Microbiology (J.A.J.P.), and Critical Care (J.V.P.), Christian Medica
  • Tarning J; From the Departments of Infectious Diseases (G.M.V., D.D., D.K., R.G.N., A.H.P., A. Manesh), Medicine (K.G., N.N., A.Z., R.I., S.G.H., S.S., T.D.S., O.C.A.), Pharmacology (B.W.A., B.S.M., A. Mathew), Emergency Medicine (K.P.P.A.), Microbiology (J.A.J.P.), and Critical Care (J.V.P.), Christian Medica
  • Blacksell SD; From the Departments of Infectious Diseases (G.M.V., D.D., D.K., R.G.N., A.H.P., A. Manesh), Medicine (K.G., N.N., A.Z., R.I., S.G.H., S.S., T.D.S., O.C.A.), Pharmacology (B.W.A., B.S.M., A. Mathew), Emergency Medicine (K.P.P.A.), Microbiology (J.A.J.P.), and Critical Care (J.V.P.), Christian Medica
  • Peerawaranun P; From the Departments of Infectious Diseases (G.M.V., D.D., D.K., R.G.N., A.H.P., A. Manesh), Medicine (K.G., N.N., A.Z., R.I., S.G.H., S.S., T.D.S., O.C.A.), Pharmacology (B.W.A., B.S.M., A. Mathew), Emergency Medicine (K.P.P.A.), Microbiology (J.A.J.P.), and Critical Care (J.V.P.), Christian Medica
  • Waithira N; From the Departments of Infectious Diseases (G.M.V., D.D., D.K., R.G.N., A.H.P., A. Manesh), Medicine (K.G., N.N., A.Z., R.I., S.G.H., S.S., T.D.S., O.C.A.), Pharmacology (B.W.A., B.S.M., A. Mathew), Emergency Medicine (K.P.P.A.), Microbiology (J.A.J.P.), and Critical Care (J.V.P.), Christian Medica
  • Mukaka M; From the Departments of Infectious Diseases (G.M.V., D.D., D.K., R.G.N., A.H.P., A. Manesh), Medicine (K.G., N.N., A.Z., R.I., S.G.H., S.S., T.D.S., O.C.A.), Pharmacology (B.W.A., B.S.M., A. Mathew), Emergency Medicine (K.P.P.A.), Microbiology (J.A.J.P.), and Critical Care (J.V.P.), Christian Medica
  • Cheah PY; From the Departments of Infectious Diseases (G.M.V., D.D., D.K., R.G.N., A.H.P., A. Manesh), Medicine (K.G., N.N., A.Z., R.I., S.G.H., S.S., T.D.S., O.C.A.), Pharmacology (B.W.A., B.S.M., A. Mathew), Emergency Medicine (K.P.P.A.), Microbiology (J.A.J.P.), and Critical Care (J.V.P.), Christian Medica
  • Peter JV; From the Departments of Infectious Diseases (G.M.V., D.D., D.K., R.G.N., A.H.P., A. Manesh), Medicine (K.G., N.N., A.Z., R.I., S.G.H., S.S., T.D.S., O.C.A.), Pharmacology (B.W.A., B.S.M., A. Mathew), Emergency Medicine (K.P.P.A.), Microbiology (J.A.J.P.), and Critical Care (J.V.P.), Christian Medica
  • Abraham OC; From the Departments of Infectious Diseases (G.M.V., D.D., D.K., R.G.N., A.H.P., A. Manesh), Medicine (K.G., N.N., A.Z., R.I., S.G.H., S.S., T.D.S., O.C.A.), Pharmacology (B.W.A., B.S.M., A. Mathew), Emergency Medicine (K.P.P.A.), Microbiology (J.A.J.P.), and Critical Care (J.V.P.), Christian Medica
  • Day NPJ; From the Departments of Infectious Diseases (G.M.V., D.D., D.K., R.G.N., A.H.P., A. Manesh), Medicine (K.G., N.N., A.Z., R.I., S.G.H., S.S., T.D.S., O.C.A.), Pharmacology (B.W.A., B.S.M., A. Mathew), Emergency Medicine (K.P.P.A.), Microbiology (J.A.J.P.), and Critical Care (J.V.P.), Christian Medica
N Engl J Med ; 388(9): 792-803, 2023 03 02.
Article in En | MEDLINE | ID: mdl-36856615
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. (Funded by the India Alliance and Wellcome Trust; INTREST Clinical Trials Registry-India number, CTRI/2018/08/015159.).
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Scrub Typhus / Doxycycline / Azithromycin / Anti-Bacterial Agents Type of study: Clinical_trials / Guideline Limits: Animals / Humans / Middle aged Language: En Journal: N Engl J Med Year: 2023 Document type: Article
Fulltext
Add to My VHL
Print
XML
PubMed Links
Search on Google

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Scrub Typhus / Doxycycline / Azithromycin / Anti-Bacterial Agents Type of study: Clinical_trials / Guideline Limits: Animals / Humans / Middle aged Language: En Journal: N Engl J Med Year: 2023 Document type: Article