A Multi-Center Randomised Controlled Trial of Gatifloxacin versus Azithromycin for the Treatment of Uncomplicated Typhoid Fever in Children and Adults in Vietnam

被引：79

作者：

Dolecek, Christiane ^{[1
,5
,6
]}

Tran Thi Phi La ^{[3
]}

Nguyen Ngoc Rang ^{[3
]}

Le Thi Phuong ^{[4
]}

Ha Vinh ^{[2
]}

Phung Quoc Tuan ^{[1
]}

Doan Cong Du ^{[3
]}

Nguyen Thi Be Bay ^{[3
]}

Duong Thanh Long ^{[3
]}

Luong Bich Ha ^{[3
]}

Nguyen Trung Binh ^{[3
]}

Nguyen Thi Anh Hong ^{[3
]}

Pham Ngoc Dung ^{[3
]}

Mai Ngoc Lanh ^{[4
]}

Phan Van Be Bay ^{[4
]}

Vo Anh Ho ^{[4
]}

Nguyen Van Minh Hoang ^{[2
]}

Tran Thu Thi Nga ^{[1
,2
]}

Tran Thuy Chau ^{[2
]}

Schultsz, Constance ^{[1
,5
]}

Dunstan, Sarah J. ^{[1
,5
]}

Stepniewska, Kasia ^{[1
,5
]}

Campbell, James Ian ^{[1
,5
]}

To Song Diep ^{[2
]}

Basnyat, Buddha ^{[7
]}

Nguyen Van Vinh Chau ^{[2
]}

Nguyen Van Sach ^{[3
]}

Nguyen Tran Chinh ^{[2
]}

Tran Tinh Hien ^{[2
]}

Farrar, Jeremy ^{[1
,5
,6
]}

机构：

[1] Univ Oxford, Clin Res Unit, Hosp Trop Dis, Ho Chi Minh City, Vietnam

[2] Hosp Trop Dis, Ho Chi Minh City, Vietnam

[3] An Giang Provincial Hosp, Long Xuyen, Vietnam

[4] Dong Thap Provincial Hosp, Cao Lanh, Dong Thap, Vietnam

[5] John Radcliffe Hosp, Nuffield Dept Clin Med, Oxford, England

[6] London Sch Hyg & Trop Med, London, England

[7] Patan Hosp, Lagankhel, Nepal

来源：

PLOS ONE | 2008年 / 3卷 / 05期

基金：

英国惠康基金;

关键词：

D O I：

10.1371/journal.pone.0002188

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Background: Drug resistant typhoid fever is a major clinical problem globally. Many of the first line antibiotics, including the older generation fluoroquinolones, ciprofloxacin and ofloxacin, are failing. Objectives: We performed a randomised controlled trial to compare the efficacy and safety of gatifloxacin (10 mg/kg/day) versus azithromycin (20 mg/kg/day) as a once daily oral dose for 7 days for the treatment of uncomplicated typhoid fever in children and adults in Vietnam. Methods: An open-label multi-centre randomised trial with pre-specified per protocol analysis and intention to treat analysis was conducted. The primary outcome was fever clearance time, the secondary outcome was overall treatment failure (clinical or microbiological failure, development of typhoid fever-related complications, relapse or faecal carriage of S. typhi). Principal Findings: We enrolled 358 children and adults with suspected typhoid fever. There was no death in the study. 287 patients had blood culture confirmed typhoid fever, 145 patients received gatifloxacin and 142 patients received azithromycin. The median FCT was 106 hours in both treatment arms (95% Confidence Interval [CI]; 94-118 hours for gatifloxacin versus 88-112 hours for azithromycin), (logrank test p = 0.984, HR [95% CI] = 1.0 [0.80-1.26]). Overall treatment failure occurred in 13/145 (9%) patients in the gatifloxacin group and 13/140 (9.3%) patients in the azithromycin group, (logrank test p = 0.854, HR [95% CI] = 0.93 [0.43-2.0]). 96% (254/263) of the Salmonella enterica serovar Typhi isolates were resistant to nalidixic acid and 58% (153/263) were multidrug resistant. Conclusions: Both antibiotics showed an excellent efficacy and safety profile. Both gatifloxacin and azithromycin can be recommended for the treatment of typhoid fever particularly in regions with high rates of multidrug and nalidixic acid resistance. The cost of a 7-day treatment course of gatifloxacin is approximately one third of the cost of azithromycin in Vietnam. Trial Registration: Controlled-Trials.com ISRCTN67946944

引用

页数：11

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