A multi-center randomized trial to assess the efficacy of gatifloxacin versus ciprofloxacin for the treatment of shigellosis in Vietnamese children

• Published in: PLoS neglected tropical diseases Vol. 5; no. 8; p. e1264
• Main Authors: Vinh, Ha, Anh, Vo Thi Cuc, Anh, Nguyen Duc, Campbell, James I, Hoang, Nguyen Van Minh, Nga, Tran Vu Thieu, Nhu, Nguyen Thi Khanh, Minh, Pham Van, Thuy, Cao Thu, Duy, Pham Thanh, Phuong, Le Thi, Loan, Ha Thi, Chinh, Mai Thu, Thao, Nguyen Thi Thu, Tham, Nguyen Thi Hong, Mong, Bui Li, Bay, Phan Van Be, Day, Jeremy N, Dolecek, Christiane, Lan, Nguyen Phu Huong, Diep, To Song, Farrar, Jeremy J, Chau, Nguyen Van Vinh, Wolbers, Marcel, Baker, Stephen
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.08.2011; Public Library of Science (PLoS)
• Subjects: Acids; Anti-Bacterial Agents - adverse effects; Anti-Bacterial Agents - therapeutic use; Antimicrobial agents; Biology; Child, Preschool; Children & youth; Ciprofloxacin - therapeutic use; Clinical trials; Comparative analysis; Developing countries; Drug resistance in microorganisms; Drug therapy; Dysentery; Dysentery, Bacillary - blood; Dysentery, Bacillary - drug therapy; Dysentery, Bacillary - metabolism; Feces - microbiology; Female; Fluoroquinolones - adverse effects; Fluoroquinolones - therapeutic use; Gatifloxacin; Health aspects; Hospitalization; Hospitals; Humans; Hyperglycemia - microbiology; Hypoglycemia - microbiology; Infant; Infections; LDCs; Male; Medicine; Pediatrics; Proportional Hazards Models; Public health; Quinolone antibacterial agents; Quinolones; Risk factors; Shigella - isolation & purification; Shigellosis; Treatment Outcome; Tropical diseases; Vietnam; Vietnam; Fluoroquinolones; Humans; Proportional Hazards Models; Child, Preschool; Infant; Male; Treatment Outcome; Hypoglycemia; Anti-Bacterial Agents; Hyperglycemia; Vietnam; Hospitals; Female; Dysentery, Bacillary; Feces; Ciprofloxacin; Shigella
• ISSN: 1935-2735; 1935-2727; 1935-2735
• DOI: 10.1371/journal.pntd.0001264

The bacterial genus Shigella is the leading cause of dysentery. There have been significant increases in the proportion of Shigella isolated that demonstrate resistance to nalidixic acid. While nalidixic acid is no longer considered as a therapeutic agent for shigellosis, the fluoroquinolone ciprofloxacin is the current recommendation of the World Health Organization. Resistance to nalidixic acid is a marker of reduced susceptibility to older generation fluoroquinolones, such as ciprofloxacin. We aimed to assess the efficacy of gatifloxacin versus ciprofloxacin in the treatment of uncomplicated shigellosis in children. We conducted a randomized, open-label, controlled trial with two parallel arms at two hospitals in southern Vietnam. The study was designed as a superiority trial and children with dysentery meeting the inclusion criteria were invited to participate. Participants received either gatifloxacin (10 mg/kg/day) in a single daily dose for 3 days or ciprofloxacin (30 mg/kg/day) in two divided doses for 3 days. The primary outcome measure was treatment failure; secondary outcome measures were time to the cessation of individual symptoms. Four hundred and ninety four patients were randomized to receive either gatifloxacin (n=249) or ciprofloxacin (n=245), of which 107 had a positive Shigella stool culture. We could not demonstrate superiority of gatifloxacin and observed similar clinical failure rate in both groups (gatifloxacin; 12.0% and ciprofloxacin; 11.0%, p=0.72). The median (inter-quartile range) time from illness onset to cessation of all symptoms was 95 (66-126) hours for gatifloxacin recipients and 93 (68-120) hours for the ciprofloxacin recipients (Hazard Ratio [95%CI]=0.98 [0.82-1.17], p=0.83). We conclude that in Vietnam, where nalidixic acid resistant Shigellae are highly prevalent, ciprofloxacin and gatifloxacin are similarly effective for the treatment of acute shigellosis.