A Multi-Center Randomized Trial to Assess the Efficacy of Gatifloxacin versus Ciprofloxacin for the Treatment of Shigellosis in Vietnamese Children

BackgroundThe 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. Methodology/Principal FindingsWe 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). ConclusionsWe conclude that in Vietnam, where nalidixic acid resistant Shigellae are highly prevalent, ciprofloxacin and gatifloxacin are similarly effective for the treatment of acute shigellosis. Trial RegistrationControlled trials number ISRCTN55945881研究背景 志贺氏菌属（Shigella）是引发细菌性痢疾的首要致病菌。近年来，临床分离株中对萘啶酸（nalidixic acid）耐药的志贺氏菌占比显著升高。尽管萘啶酸已不再被推荐用于志贺菌病的治疗，但氟喹诺酮类药物环丙沙星（ciprofloxacin）是目前世界卫生组织（World Health Organization）推荐的一线治疗药物。对萘啶酸耐药可作为志贺氏菌对环丙沙星等老一代氟喹诺酮类药物敏感性降低的标志物。本研究旨在评估加替沙星（gatifloxacin）对比环丙沙星治疗儿童单纯性细菌性痢疾的临床疗效。 研究方法与主要结果 本研究在越南南部两家医院开展了一项随机、开放标签、平行对照优效性试验。纳入符合入组标准的细菌性痢疾儿童受试者，按要求随机分为两组，分别接受3天疗程的治疗：加替沙星组予10mg/kg/日剂量，每日单次给药；环丙沙星组予30mg/kg/日剂量，分两次给药。本研究的主要结局指标为治疗失败率，次要结局指标为各单项临床症状消失所需时间。 共494名患者被随机分配至加替沙星组（n=249）与环丙沙星组（n=245），其中107例患者粪便志贺氏菌培养结果呈阳性。本研究未证实加替沙星的临床优效性，两组临床失败率相近：加替沙星组为12.0%，环丙沙星组为11.0%（p=0.72）。加替沙星组患儿从发病至所有症状消失的中位（四分位间距）时间为95（66~126）小时，环丙沙星组为93（68~120）小时（风险比[95%置信区间]=0.98[0.82~1.17]，p=0.83）。 研究结论 本研究结果显示，在萘啶酸耐药志贺氏菌高度流行的越南地区，环丙沙星与加替沙星治疗急性细菌性痢疾的临床疗效相当。 试验注册 临床试验编号：ISRCTN55945881