Intravenous Doxycycline, Azithromycin, or Both for Severe Scrub Typhus

被引：33

作者：

Varghese, George M. ^{[1
,2
]}

Dayanand, Divya ^{[2
]}

Gunasekaran, Karthik ^{[3
]}

Kundu, Debasree ^{[2
]}

Wyawahare, Mukta ^{[8
]}

Sharma, Navneet ^{[9
]}

Chaudhry, Dhruva ^{[11
]}

Mahajan, Sanjay K. ^{[12
]}

Saravu, Kavitha ^{[13
]}

Aruldhas, Blessed W. ^{[4
]}

Mathew, Binu S. ^{[4
]}

Nair, Roshini G. ^{[2
]}

Newbigging, Nalini ^{[3
]}

Mathew, Aswathy ^{[4
]}

Abhilash, Kundavaram P. P. ^{[5
]}

Biswal, Manisha ^{[10
]}

Prasad, Ann H. ^{[2
]}

Zachariah, Anand ^{[3
]}

Iyadurai, Ramya ^{[3
]}

Hansdak, Samuel G. ^{[3
]}

Sathyendra, Sowmya ^{[3
]}

Sudarsanam, Thambu D. ^{[3
]}

Prakash, John A. J. ^{[6
]}

Manesh, Abi ^{[2
]}

Mohan, Alladi ^{[14
]}

Tarning, Joel ^{[15
,16
]}

Blacksell, Stuart D. ^{[15
,16
]}

Peerawaranun, Pimnara ^{[15
]}

Waithira, Naomi ^{[15
,16
]}

Mukaka, Mavuto ^{[15
,16
]}

Cheah, Phaik Yeong ^{[15
,16
]}

Peter, John V. ^{[7
]}

Abraham, Ooriapadickal C. ^{[3
]}

Day, Nicholas P. J. ^{[15
,16
]}

机构：

[1] Christian Med Coll & Hosp, Dept Infect Dis, Vellore 632004, India

[2] Christian Med Coll & Hosp, Dept Infect Dis, Vellore, India

[3] Christian Med Coll & Hosp, Dept Med, Vellore, India

[4] Christian Med Coll & Hosp, Dept Pharmacol, Vellore, India

[5] Christian Med Coll & Hosp, Dept Emergency Med, Vellore, India

[6] Christian Med Coll & Hosp, Dept Microbiol, Vellore, India

[7] Christian Med Coll & Hosp, Dept Crit Care, Vellore, India

[8] Jawaharlal Inst Post Grad Med Educ & Res, Dept Med, Pondicherry, India

[9] Post Grad Inst Med Educ & Res, Dept Internal Med, Chandigarh, India

[10] Post Grad Inst Med Educ & Res, Dept Microbiol, Chandigarh, India

[11] Pandit Bhagwat Dayal Sharma Post Grad Inst Med Sci, Dept Pulm Care & Crit Med, Rohtak, India

[12] Indira Gandhi Med Coll, Dept Med, Shimla, India

[13] Manipal Acad Higher Educ, Kasturba Med Coll, Dept Infect Dis, Manipal, India

[14] Sri Venkateswara Inst Med Sci, Dept Med, Tirupati, India

[15] Mahidol Univ, Fac Trop Med, Mahidol Oxford Trop Med Res Unit, Bangkok, Thailand

[16] Univ Oxford, Ctr Trop Med & Global Hlth, Nuffield Dept Med, Oxford, England

来源：

NEW ENGLAND JOURNAL OF MEDICINE | 2023年 / 388卷 / 09期

基金：

英国惠康基金;

关键词：

MORTALITY; PREDICTORS; CHILDREN; PROFILE;

D O I：

10.1056/NEJMoa2208449

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

BackgroundThe appropriate antibiotic treatment for severe scrub typhus, a neglected but widespread reemerging zoonotic infection, is unclear.MethodsIn 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.ResultsAmong 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.ConclusionsCombination 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, .)

引用

页码：792 / 803

页数：12

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