A multi-center randomised controlled trial of gatifloxacin versus azithromycin for the treatment of uncomplicated typhoid fever in children and adults in Vietnam.

Abstract

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.

• Authors: Christiane Dolecek, Thi Phi La Tran, Ngoc Rang Nguyen, Thi Phuong Le, Vinh Ha, Quoc Tuan Phung, Cong Du Doan, Thi Be Bay Nguyen, Thanh Long Duong, Bich Ha Luong, Trung Binh Nguyen, Thi Anh Hong Nguyen, Ngoc Dung Pham, Ngoc Lanh Mai, Van Be Bay Phan, Anh Ho Vo, Van Minh Hoang Nguyen, Thu Thi Nga Tran, Thuy Chau Tran, Constance Schultsz, Sarah J Dunstan, Kasia Stepniewska, James Ian Campbell, Song Diep To, Buddha Basnyat, Van Vinh Chau Nguyen, Van Sach Nguyen, Tran Chinh Nguyen, Tinh Hien Tran, Jeremy Farrar
• Journal: PloS one (PLoS One) Vol. 3 Issue 5 Pg. e2188 (May 21 2008) ISSN: 1932-6203 [Electronic] United States
• PMID: 18493312 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Bacterial Agents
• Fluoroquinolones
• Azithromycin
• Gatifloxacin

Topics

• Adult
• Anti-Bacterial Agents (therapeutic use)
• Azithromycin (therapeutic use)
• Child
• Fluoroquinolones (therapeutic use)
• Gatifloxacin
• Humans
• Microbial Sensitivity Tests
• Salmonella (classification, drug effects)
• Species Specificity
• Typhoid Fever (drug therapy)