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


OBJECTIVE
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).


RESULTS
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.


BACKGROUND
Controlled-Trials.com ISRCTN67946944.
Dolecek
Christiane
C
Oxford University Clinical Research Unit, The Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam. cdolecek@oucru.org
Tran
Thi Phi La
TP
Nguyen
Ngoc Rang
NR
Le
Thi Phuong
TP
Ha
Vinh
V
Phung
Quoc Tuan
QT
Doan
Cong Du
CD
Nguyen
Thi Be Bay
TB
Duong
Thanh Long
TL
Luong
Bich Ha
BH
Nguyen
Trung Binh
TB
Nguyen
Thi Anh Hong
TA
Pham
Ngoc Dung
ND
Mai
Ngoc Lanh
NL
Phan
Van Be Bay
VB
Vo
Anh Ho
AH
Nguyen
Van Minh Hoang
VM
Tran
Thu Thi Nga
TT
Tran
Thuy Chau
TC
Schultsz
Constance
C
Dunstan
Sarah J
SJ
Stepniewska
Kasia
K
Campbell
James Ian
JI
To
Song Diep
SD
Basnyat
Buddha
B
Nguyen
Van Vinh Chau
VV
Nguyen
Van Sach
VS
Nguyen
Tran Chinh
TC
Tran
Tinh Hien
TH
Farrar
Jeremy
J
D000328:Adult; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D017963:Azithromycin / Q000627:therapeutic use*; D002648:Child; D024841:Fluoroquinolones / Q000627:therapeutic use*; D000077734:Gatifloxacin; D006801:Humans; D008826:Microbial Sensitivity Tests; D012475:Salmonella / Q000145:classification / Q000187:drug effects; D013045:Species Specificity; D014435:Typhoid Fever / Q000188:drug therapy*
D000900:Anti-Bacterial Agents; D024841:Fluoroquinolones; D017963:Azithromycin; D000077734:Gatifloxacin