title: Gatifloxacin versus ofloxacin for the treatment of uncomplicated enteric fever in Nepal: an open-label, randomized, controlled trial.
abstract: BACKGROUND
  Fluoroquinolones are the most commonly used group of antimicrobials for the treatment of enteric fever, but no direct comparison between two fluoroquinolones has been performed in a large randomised trial. An open-label randomized trial was conducted to investigate whether gatifloxacin is more effective than ofloxacin in the treatment of uncomplicated enteric fever caused by nalidixic acid-resistant Salmonella enterica serovars Typhi and Paratyphi A.
  
  
  RESULTS
  Adults and children clinically diagnosed with uncomplicated enteric fever were enrolled in the study to receive gatifloxacin (10 mg/kg/day) in a single dose or ofloxacin (20 mg/kg/day) in two divided doses for 7 days. Patients were followed for six months. The primary outcome was treatment failure in patients infected with nalidixic acid resistant isolates. 627 patients with a median age of 17 (IQR 9-23) years were randomised. Of the 218 patients with culture confirmed enteric fever, 170 patients were infected with nalidixic acid-resistant isolates. In the ofloxacin group, 6 out of 83 patients had treatment failure compared to 5 out of 87 in the gatifloxacin group (hazard ratio [HR] of time to failure 0.81, 95% CI 0.25 to 2.65, p = 0.73). The median time to fever clearance was 4.70 days (IQR 2.98-5.90) in the ofloxacin group versus 3.31 days (IQR 2.29-4.75) in the gatifloxacin group (HR = 1.59, 95% CI 1.16 to 2.18, p = 0.004). The results in all blood culture-confirmed patients and all randomized patients were comparable.
  
  
  CONCLUSIONS
  Gatifloxacin was not superior to ofloxacin in preventing failure, but use of gatifloxacin did result in more prompt fever clearance time compared to ofloxacin.
  
  
  BACKGROUND
  ISRCTN 63006567 (www.controlled-trials.com).
authors.affiliation: Oxford University Clinical Research Unit-Nepal, Patan Academy of Health Sciences, Patan Hospital, Patan, Nepal.
authors.forename: Samir
authors.initials: S
authors.lastname: Koirala
authors.forename: Buddha
authors.initials: B
authors.lastname: Basnyat
authors.forename: Amit
authors.initials: A
authors.lastname: Arjyal
authors.forename: Olita
authors.initials: O
authors.lastname: Shilpakar
authors.forename: Kabina
authors.initials: K
authors.lastname: Shrestha
authors.forename: Rishav
authors.initials: R
authors.lastname: Shrestha
authors.forename: Upendra Man
authors.initials: UM
authors.lastname: Shrestha
authors.forename: Krishna
authors.initials: K
authors.lastname: Agrawal
authors.forename: Kanika Deshpande
authors.initials: KD
authors.lastname: Koirala
authors.forename: Sudeep Dhoj
authors.initials: SD
authors.lastname: Thapa
authors.forename: Abhilasha
authors.initials: A
authors.lastname: Karkey
authors.forename: Sabina
authors.initials: S
authors.lastname: Dongol
authors.forename: Abhishek
authors.initials: A
authors.lastname: Giri
authors.forename: Mila
authors.initials: M
authors.lastname: Shakya
authors.forename: Kamal Raj
authors.initials: KR
authors.lastname: Pathak
authors.forename: James
authors.initials: J
authors.lastname: Campbell
authors.forename: Stephen
authors.initials: S
authors.lastname: Baker
authors.forename: Jeremy
authors.initials: J
authors.lastname: Farrar
authors.forename: Marcel
authors.initials: M
authors.lastname: Wolbers
authors.forename: Christiane
authors.initials: C
authors.lastname: Dolecek
mesh_terms: D000293:Adolescent; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D002648:Child; D024881:Drug Resistance, Bacterial; D005260:Female; D024841:Fluoroquinolones / Q000008:administration & dosage*; D000077734:Gatifloxacin; D006801:Humans; D008297:Male; D009390:Nepal; D015242:Ofloxacin / Q000008:administration & dosage*; D012482:Salmonella paratyphi A / Q000187:drug effects / Q000302:isolation & purification; D012485:Salmonella typhi / Q000187:drug effects / Q000302:isolation & purification; D017211:Treatment Failure; D014435:Typhoid Fever / Q000188:drug therapy*; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D024841:Fluoroquinolones; D015242:Ofloxacin; D000077734:Gatifloxacin