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Antimicrobial Agents and Chemotherapy, March 2007, p. 819-825, Vol. 51, No. 3
0066-4804/07/$08.00+0     doi:10.1128/AAC.00447-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

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

Christopher M. Parry,1,4* Vo Anh Ho,2 Le Thi Phuong,2 Phan Van Be Bay,2 Mai Ngoc Lanh,2 Le Thanh Tung,2 Nguyen Thi Hong Tham,2 John Wain,1,4,{dagger} Tran Tinh Hien,3 and Jeremy J. Farrar1,4

Oxford University Clinical Research Unit,1 Hospital for Tropical Diseases, Ho Chi Minh City,3 Dong Thap Provincial Hospital, Cao Lanh City, Dong Thap Province, Vietnam,2 Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, John Radcliffe Hospital, Oxford OX3 9DU, United Kingdom4

Received 10 April 2006/ Returned for modification 16 May 2006/ Accepted 27 November 2006

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, Nar) 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/Nar 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 Nar. 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 (Nar) can be successfully treated with a 7-day course of azithromycin.

* Corresponding author. Present address: Department of Medical Microbiology and Genitourinary Medicine, Duncan Building, University of Liverpool, Liverpool L69 3GA, United Kingdom. Phone: 44 151 706 4381. Fax: 44 151 706 5805. E-mail: cmparry{at}liv.ac.uk.

{triangledown} Published ahead of print on 4 December 2006.

{dagger} Present address: The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, United Kingdom.

Antimicrobial Agents and Chemotherapy, March 2007, p. 819-825, Vol. 51, No. 3
0066-4804/07/$08.00+0     doi:10.1128/AAC.00447-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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