Intravenous Doxycycline, Azithromycin, or Both for Severe Scrub Typhus.

Animals Humans Middle Aged Anti-Bacterial Agents / administration & dosage Azithromycin / administration & dosage Doxycycline / administration & dosage Scrub Typhus / drug therapy Zoonoses Double-Blind Method Drug Therapy, Combination Administration, Intravenous

Journal

The New England journal of medicine

ISSN: 1533-4406

Titre abrégé: N Engl J Med

Pays: United States

ID NLM: 0255562

Informations de publication

Date de publication:
02 03 2023

Historique:

entrez: 1 3 2023

pubmed: 2 3 2023

medline: 4 3 2023

Statut: ppublish

Résumé

The appropriate antibiotic treatment for severe scrub typhus, a neglected but widespread reemerging zoonotic infection, is unclear. 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. 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. 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.).

Sections du résumé

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.).

Identifiants

DOI: 10.1056/NEJMoa2208449 PMID: 36856615 PMC: PMC7614458

pubmed: 36856615

doi: 10.1056/NEJMoa2208449

pmc: PMC7614458

mid: EMS173299

doi:

Substances chimiques

Anti-Bacterial Agents 0

Azithromycin 83905-01-5

Doxycycline N12000U13O

Banques de données

CTRI

['CTRI/2018/08/015159']

Types de publication

Comparative Study Journal Article Multicenter Study Randomized Controlled Trial Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

Pagination

792-803

Subventions

Organisme : DBT-Wellcome Trust India Alliance

ID : IA/CPHS/16/1/502679

Pays : India

Organisme : Wellcome Trust

ID : 220211/Z/20/Z

Pays : United Kingdom

Investigateurs

Emily Devasagayam (E)

Indhuja Irudhayanathan (I)

Merylin Sebastian (M)

Kavitha Kannan (K)

Rajiv Karthik (R)

M Vivekanandan (M)

T Kadhiravan (T)

Bettadpura Suryanarayana Shamanna (BS)

Kolar Vishwanath Vinod (KV)

Chanaveerappa Bammigatti (C)

Ashok Kumar Pannu (AK)

Priyanka Sharma (P)

Samir Malhotra (S)

Neeraj Singla (N)

Diksha Tyagi (D)

Manjunath B Govindagoudar (MB)

Ankita Chaudhary (A)

Pawan K Singh (PK)

Kiran Chunduru (K)

H Manjunath Hande (HM)

Rama Bhat (R)

Mukhyaprana M Prabhu (MM)

Barkur Ananthakrishna Shastry (BA)

Raviraja V Acharya (RV)

K N Shivashankara (KN)

Jayaraj Mymbilly Balakrishnan (JM)

Vishal Shanbhag (V)

Kanchi Mitra Bhargav (KM)

Brian Mutinda (B)

Paul Newton (P)

Commentaires et corrections

Type : CommentIn

Informations de copyright

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