title: 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.
  
  
  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.
authors.affiliation: Oxford University Clinical Research Unit, The Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam. cdolecek@oucru.org
authors.forename: Christiane
authors.initials: C
authors.lastname: Dolecek
authors.forename: Thi Phi La
authors.initials: TP
authors.lastname: Tran
authors.forename: Ngoc Rang
authors.initials: NR
authors.lastname: Nguyen
authors.forename: Thi Phuong
authors.initials: TP
authors.lastname: Le
authors.forename: Vinh
authors.initials: V
authors.lastname: Ha
authors.forename: Quoc Tuan
authors.initials: QT
authors.lastname: Phung
authors.forename: Cong Du
authors.initials: CD
authors.lastname: Doan
authors.forename: Thi Be Bay
authors.initials: TB
authors.lastname: Nguyen
authors.forename: Thanh Long
authors.initials: TL
authors.lastname: Duong
authors.forename: Bich Ha
authors.initials: BH
authors.lastname: Luong
authors.forename: Trung Binh
authors.initials: TB
authors.lastname: Nguyen
authors.forename: Thi Anh Hong
authors.initials: TA
authors.lastname: Nguyen
authors.forename: Ngoc Dung
authors.initials: ND
authors.lastname: Pham
authors.forename: Ngoc Lanh
authors.initials: NL
authors.lastname: Mai
authors.forename: Van Be Bay
authors.initials: VB
authors.lastname: Phan
authors.forename: Anh Ho
authors.initials: AH
authors.lastname: Vo
authors.forename: Van Minh Hoang
authors.initials: VM
authors.lastname: Nguyen
authors.forename: Thu Thi Nga
authors.initials: TT
authors.lastname: Tran
authors.forename: Thuy Chau
authors.initials: TC
authors.lastname: Tran
authors.forename: Constance
authors.initials: C
authors.lastname: Schultsz
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Dunstan
authors.forename: Kasia
authors.initials: K
authors.lastname: Stepniewska
authors.forename: James Ian
authors.initials: JI
authors.lastname: Campbell
authors.forename: Song Diep
authors.initials: SD
authors.lastname: To
authors.forename: Buddha
authors.initials: B
authors.lastname: Basnyat
authors.forename: Van Vinh Chau
authors.initials: VV
authors.lastname: Nguyen
authors.forename: Van Sach
authors.initials: VS
authors.lastname: Nguyen
authors.forename: Tran Chinh
authors.initials: TC
authors.lastname: Nguyen
authors.forename: Tinh Hien
authors.initials: TH
authors.lastname: Tran
authors.forename: Jeremy
authors.initials: J
authors.lastname: Farrar
mesh_terms: 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*
chemical_list: D000900:Anti-Bacterial Agents; D024841:Fluoroquinolones; D017963:Azithromycin; D000077734:Gatifloxacin