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Gatifloxacin versus ceftriaxone for uncomplicated enteric fever in Nepal: an open-label, two-centre, randomised controlled trial.

Arjyal A, Basnyat B, Nhan HT, Koirala S, Giri A, Joshi N, Shakya M, Pathak KR, Mahat SP, Prajapati SP, Adhikari N, Thapa R, Merson L, Gajurel D, Lamsal K, Lamsal D, Yadav BK, Shah G, Shrestha P, Dongol S, Karkey A, Thompson CN, Thieu NT, Thanh DP, Baker S, Thwaites GE, Wolbers M, Dolecek C - Lancet Infect Dis (2016)

Bottom Line: Because treatment with third-generation cephalosporins is associated with slow clinical improvement and high relapse burden for enteric fever, whereas the fluoroquinolone gatifloxacin is associated with rapid fever clearance and low relapse burden, we postulated that gatifloxacin would be superior to the cephalosporin ceftriaxone in treating enteric fever.In the culture-confirmed population, 16 (26%) of 62 patients who received gatifloxacin failed treatment, compared with four (7%) of 54 who received ceftriaxone (HR 0·24 [95% CI 0·08-0·73]; p=0·01).Wellcome Trust and Li Ka Shing Foundation.

View Article: PubMed Central - PubMed

Affiliation: Oxford University Clinical Research Unit, Patan Academy of Health Sciences, Kathmandu, Nepal.

No MeSH data available.


Related in: MedlinePlus

Trial profileSalmonella enterica Typhi or Salmonella enterica Paratyphi A were isolated from the blood of patients with culture-confirmed enteric fever.
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fig1: Trial profileSalmonella enterica Typhi or Salmonella enterica Paratyphi A were isolated from the blood of patients with culture-confirmed enteric fever.

Mentions: Between Sept 18, 2011, and July 14, 2014, we screened 725 patients with suspected enteric fever for enrolment (figure 1). The data and safety monitoring board reviewed the outcome data after 100 patients, and then 200 patients, were randomised. At the 200-patient review, the board requested an additional review within 3 months of MICs against ciprofloxacin and gatifloxacin against all bacterial isolates. Data from 109 culture-confirmed patients (and 233 patients in total) were analysed at this additional review. A comparison of treatment failures between treatment groups did not cross the predefined Haybittle-Peto stopping boundary23 of p less than 0·001 (overall or in any subgroup), but the emergence of S Typhi strains with MICs against ciprofloxacin that were greater than 16 μg/mL and against gatifloxacin that were greater than 1 μg/mL, and a significant difference (p=0·0002 for susceptive vs resistant strains in the gatifloxacin group) in treatment response between patients with fluoroquinolone-resistant strains and those with susceptible strains, led the board to recommend stopping the trial on clinical grounds supported by data on the changing in-vitro susceptibility.


Gatifloxacin versus ceftriaxone for uncomplicated enteric fever in Nepal: an open-label, two-centre, randomised controlled trial.

Arjyal A, Basnyat B, Nhan HT, Koirala S, Giri A, Joshi N, Shakya M, Pathak KR, Mahat SP, Prajapati SP, Adhikari N, Thapa R, Merson L, Gajurel D, Lamsal K, Lamsal D, Yadav BK, Shah G, Shrestha P, Dongol S, Karkey A, Thompson CN, Thieu NT, Thanh DP, Baker S, Thwaites GE, Wolbers M, Dolecek C - Lancet Infect Dis (2016)

Trial profileSalmonella enterica Typhi or Salmonella enterica Paratyphi A were isolated from the blood of patients with culture-confirmed enteric fever.
© Copyright Policy - CC BY
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4835582&req=5

fig1: Trial profileSalmonella enterica Typhi or Salmonella enterica Paratyphi A were isolated from the blood of patients with culture-confirmed enteric fever.
Mentions: Between Sept 18, 2011, and July 14, 2014, we screened 725 patients with suspected enteric fever for enrolment (figure 1). The data and safety monitoring board reviewed the outcome data after 100 patients, and then 200 patients, were randomised. At the 200-patient review, the board requested an additional review within 3 months of MICs against ciprofloxacin and gatifloxacin against all bacterial isolates. Data from 109 culture-confirmed patients (and 233 patients in total) were analysed at this additional review. A comparison of treatment failures between treatment groups did not cross the predefined Haybittle-Peto stopping boundary23 of p less than 0·001 (overall or in any subgroup), but the emergence of S Typhi strains with MICs against ciprofloxacin that were greater than 16 μg/mL and against gatifloxacin that were greater than 1 μg/mL, and a significant difference (p=0·0002 for susceptive vs resistant strains in the gatifloxacin group) in treatment response between patients with fluoroquinolone-resistant strains and those with susceptible strains, led the board to recommend stopping the trial on clinical grounds supported by data on the changing in-vitro susceptibility.

Bottom Line: Because treatment with third-generation cephalosporins is associated with slow clinical improvement and high relapse burden for enteric fever, whereas the fluoroquinolone gatifloxacin is associated with rapid fever clearance and low relapse burden, we postulated that gatifloxacin would be superior to the cephalosporin ceftriaxone in treating enteric fever.In the culture-confirmed population, 16 (26%) of 62 patients who received gatifloxacin failed treatment, compared with four (7%) of 54 who received ceftriaxone (HR 0·24 [95% CI 0·08-0·73]; p=0·01).Wellcome Trust and Li Ka Shing Foundation.

View Article: PubMed Central - PubMed

Affiliation: Oxford University Clinical Research Unit, Patan Academy of Health Sciences, Kathmandu, Nepal.

No MeSH data available.


Related in: MedlinePlus