Randomized Controlled Comparison of Ofloxacin, Azithromycin, and an Ofloxacin-Azithromycin Combination for Treatment of Multidrug-Resistant and Nalidixic Acid-Resistant Typhoid Fever

<jats:title>ABSTRACT</jats:title> <jats:p>Isolates of <jats:italic>Salmonella enterica</jats:italic> serovar Typhi that are multidrug resistant (MDR, resistant to chloramphenicol, ampicillin, and trimethoprim-sulfamethoxazole) and have reduced susceptibility to fluoroquinolones (nalidixic acid resistant, Na<jats:sup>r</jats:sup>) 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<jats:sup>r</jats:sup> 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 <jats:italic>S. enterica</jats:italic> serovar Typhi, 1 <jats:italic>Salmonella enterica</jats:italic> serovar Paratyphi A). Eighty-seven percent (163/187) of the patients were children; of the <jats:italic>S. enterica</jats:italic> serovar Typhi isolates, 88% (165/187) were MDR and 93% (173/187) were Na<jats:sup>r</jats:sup>. The clinical cure rate was 64% (40/63) with ofloxacin, 76% (47/62) with ofloxacin-azithromycin, and 82% (51/62) with azithromycin (<jats:italic>P</jats:italic> = 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]) (<jats:italic>P</jats:italic> &lt; 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 (<jats:italic>P</jats:italic> = 0.006). Both antibiotics were well tolerated. Uncomplicated typhoid fever due to isolates of MDR <jats:italic>S. enterica</jats:italic> serovar Typhi with reduced susceptibility to fluoroquinolones (Na<jats:sup>r</jats:sup>) can be successfully treated with a 7-day course of azithromycin.</jats:p>