Isolates of Salmonella enterica serovar Typhi that are multidrug resistant (MDR, resistant to
chloramphenicol,
ampicillin, and
trimethoprim-sulfamethoxazole) and have reduced susceptibility to
fluoroquinolones (
nalidixic acid resistant, Na(r)) are common in Asia. The optimum treatment for
infections caused by such isolates is not established. This study compared different antimicrobial regimens for the treatment of MDR/Na(r)
typhoid fever. Vietnamese children and adults with uncomplicated
typhoid fever were entered into an open randomized controlled trial.
Ofloxacin (20 mg/kg of
body weight/day for 7 days),
azithromycin (10 mg/kg/day for 7 days), and
ofloxacin (15 mg/kg/day for 7 days) combined with
azithromycin (10 mg/kg/day for the first 3 days) were compared. Of the 241 enrolled patients, 187 were eligible for analysis (186 S. enterica serovar Typhi, 1 Salmonella enterica serovar Paratyphi A). Eighty-seven percent (163/187) of the patients were children; of the S. enterica serovar Typhi isolates, 88% (165/187) were MDR and 93% (173/187) were Na(r). The clinical cure rate was 64% (40/63) with
ofloxacin, 76% (47/62) with
ofloxacin-
azithromycin, and 82% (51/62) with
azithromycin (P = 0.053). The mean (95% confidence interval [CI])
fever clearance time for patients treated with
azithromycin (5.8 days [5.1 to 6.5 days]) was shorter than that for patients treated with
ofloxacin-
azithromycin (7.1 days [6.2 to 8.1 days]) and
ofloxacin (8.2 days [7.2 to 9.2 days]) (P < 0.001). Positive fecal carriage immediately posttreatment was detected in 19.4% (12/62) of patients treated with
ofloxacin, 6.5% (4/62) of those treated with the combination, and 1.6% (1/62) of those treated with
azithromycin (P = 0.006). Both
antibiotics were well tolerated. Uncomplicated
typhoid fever due to isolates of MDR S. enterica serovar Typhi with reduced susceptibility to
fluoroquinolones (Na(r)) can be successfully treated with a 7-day course of
azithromycin.