title: Randomized controlled comparison of ofloxacin, azithromycin, and an ofloxacin-azithromycin combination for treatment of multidrug-resistant and nalidixic acid-resistant typhoid fever.
abstract: 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.
authors.affiliation: Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam. cmparry@liv.ac.uk
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Parry
authors.forename: Vo Anh
authors.initials: VA
authors.lastname: Ho
authors.forename: Le Thi
authors.initials: le T
authors.lastname: Phuong
authors.forename: Phan Van Be
authors.initials: PV
authors.lastname: Bay
authors.forename: Mai Ngoc
authors.initials: MN
authors.lastname: Lanh
authors.forename: Le Thanh
authors.initials: le T
authors.lastname: Tung
authors.forename: Nguyen Thi Hong
authors.initials: NT
authors.lastname: Tham
authors.forename: John
authors.initials: J
authors.lastname: Wain
authors.forename: Tran Tinh
authors.initials: TT
authors.lastname: Hien
authors.forename: Jeremy J
authors.initials: JJ
authors.lastname: Farrar
mesh_terms: D000293:Adolescent; D000328:Adult; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D017963:Azithromycin / Q000627:therapeutic use*; D001772:Blood Cell Count; D002648:Child; D002675:Child, Preschool; D004338:Drug Combinations; D024901:Drug Resistance, Multiple, Bacterial; D005260:Female; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D009268:Nalidixic Acid / Q000494:pharmacology*; D015242:Ofloxacin / Q000627:therapeutic use*; D019779:Salmonella enterica / Q000187:drug effects; D016896:Treatment Outcome; D014435:Typhoid Fever / Q000188:drug therapy* / Q000382:microbiology
chemical_list: D000900:Anti-Bacterial Agents; D004338:Drug Combinations; D009268:Nalidixic Acid; D017963:Azithromycin; D015242:Ofloxacin