Department of Infectious Diseases, Sahlgrenska University Hospital, Göteborg, Sweden.
Lancet. 2012 Aug 4;380(9840):484-90. doi: 10.1016/S0140-6736(12)60608-4. Epub 2012 Jun 21.
Acute pyelonephritis is a common infection in adult women, but there is a paucity of controlled trials of its treatment and the optimum duration of antibiotic treatment has not been properly defined. We compared the efficacy of ciprofloxacin for 7 days and 14 days in women with community-acquired acute pyelonephritis.
In a prospective, non-inferiority trial undertaken at 21 centres of infectious diseases in Sweden, women (aged ≥18 years) who were not pregnant and had a presumptive diagnosis of acute pyelonephritis were randomly assigned to oral treatment with ciprofloxacin 500 mg twice daily for 7 days or 14 days. The first week was open label. A computer-generated randomisation list in block sizes of two was used for treatment allocation in a 1:1 ratio. The study was double-blind and placebo-controlled during the second week of treatment, which was either continuation of ciprofloxacin 500 mg or placebo tablets twice daily according to the randomisation code. Patients, carers, site investigators, and trial coordinating centre staff were masked to group assignment. The primary endpoint was the clinical and bacteriological outcome 10-14 days after completion of treatment with active drug. Analysis was by per protocol. This trial is registered with EudraCT, number 2005-004992-39, and ClinicalTrials.gov, number ISRCTN73338924.
126 of 248 patients were randomly assigned to 7 days and 122 to 14 days of ciprofloxacin. 73 and 83 patients, respectively, were analysed. Short-term clinical cure occurred in 71 (97%) patients treated with ciprofloxacin for 7 days and 80 (96%) treated for 14 days (difference -0·9%; 90% CI -6·5 to 4·8; p=0·004; non-inferiority test). Cumulative efficacy at long-term follow-up was 93% in each group (68 of 73 vs 78 of 84; -0·3%; -7·4 to 7·2; p=0·015). Both regimens were well tolerated. Two patients discontinued ciprofloxacin because of myalgia with 7 days of treatment and itching exanthema with 14 days. Four (5%) of 86 patients assigned to 7 days of treatment who complied with study criteria and six (6%) of 93 assigned to 14 days reported an adverse event after the first week of treatment that was possibly or probably related to the study drug. In those assigned to 7 days, no patient had mucosal candida infection after the first week versus five treated for 14 days (p=0·036).
Our results show that acute pyelonephritis in women, including older women and those with a more severe infection, can be treated successfully and safely with oral ciprofloxacin for 7 days. Short courses of antibiotics should be favoured in an era of increasing resistance.
Swedish Strategic Programme against Antibiotic Resistance (Strama).
急性肾盂肾炎是成年女性常见的感染，但针对其治疗的对照试验较少，且抗生素治疗的最佳持续时间尚未得到恰当界定。我们比较了环丙沙星治疗社区获得性急性肾盂肾炎 7 天与 14 天的疗效。
在瑞典 21 个传染病中心进行的一项前瞻性非劣效性试验中，我们纳入了年龄≥18 岁、非妊娠且疑似急性肾盂肾炎的女性患者，将其随机分配接受口服环丙沙星 500 mg，每日 2 次，治疗 7 天或 14 天。第 1 周为开放性标签治疗。采用计算机生成的、大小为 2 的区组随机化列表，以 1:1 的比例进行治疗分配。研究在第 2 周的治疗期间为双盲和安慰剂对照，根据随机化代码，继续给予环丙沙星 500 mg 或安慰剂片剂，每日 2 次。患者、照料者、现场研究者和试验协调中心工作人员对分组情况不知情。主要终点是治疗完成后 10-14 天的临床和细菌学结局。分析采用方案设定。本试验在 EudraCT 注册，编号为 2005-004992-39，在 ClinicalTrials.gov 注册，编号为 ISRCTN73338924。
共有 248 例患者入组，126 例被随机分配至 7 天组，122 例被随机分配至 14 天组。分别有 73 例和 83 例患者被纳入分析。接受 7 天环丙沙星治疗的 71 例（97%）和接受 14 天治疗的 80 例（96%）患者在短期临床治愈（差异 0.9%；90%CI -6.5 至 4.8；p=0.004；非劣效性检验）。两组在长期随访时的累积疗效均为 93%（分别为 73 例中的 68 例和 84 例中的 78 例；差异 -0.3%；-7.4 至 7.2；p=0.015）。两种方案均耐受良好。各有 2 例患者因 7 天疗程中的肌痛和 14 天疗程中的瘙痒性出疹而停止使用环丙沙星。在接受 7 天治疗且符合研究标准的 86 例患者中，有 4 例（5%）和在接受 14 天治疗的 93 例患者中，有 6 例（6%）在第 1 周治疗后报告了可能或很可能与研究药物有关的不良事件。在接受 7 天治疗的患者中，第 1 周后没有黏膜念珠菌感染的患者，而接受 14 天治疗的患者中有 5 例（p=0.036）。
我们的结果表明，包括老年女性和感染更严重的女性在内的急性肾盂肾炎可成功且安全地接受口服环丙沙星治疗 7 天。在抗生素耐药性日益增加的时代，应提倡使用较短疗程的抗生素。
瑞典抗生素耐药性战略计划（Strama）。
