College of Basic Medical Sciences, Army Medical University, Chongqing, 400042, China.
Department of Gastroenterology, Daping Hospital, Army Medical University, 10 Changjiang Branch Road, Chongqing, 400042, China.
BMC Microbiol. 2019 Aug 5;19(1):176. doi: 10.1186/s12866-019-1558-8.
Clarithromycin-resistance is becoming a global health concern in the treatment of Helicobacter pylori (H. pylori). The mutant prevention concentration (MPC) represent the propensities of antimicrobial agents to select resistant mutants. The concentration range between the minimum inhibitory concentration (MIC) and the MPC is defined as mutant selection window (MSW). In this study, we aimed to determine the cause of increasing clarithromycin resistance by investigating the MSW for clinical isolates of H. pylori.
A retrospective subgroup, which included 68 clarithromycin-sensitive H. pylori strains, was selected from a double-blind trial. The MICs and MPCs were determined using agar plate assays. Genotypic tests were performed using Sanger sequencing. All isolates were wild-type, and 33.82% (23/68) had a 0.016 mg/L MIC, 45.59% (31/68) had a 0.031 mg/L MIC, 16.18% (11/68) had a 0.062 ≤ MIC ≤ 0.125 mg/L, and 4.41% (3/68) had a 0.25 mg/L MIC. The MPC (mg/L) of the isolates were: 0.062/0.125, 0.125/0.5, 0.25/0.25 and 1/2, respectively. The MPCs showed a moderate correlation with the MICs (r = 0.65, P < 0.0001). Using published data and MPC, we calculated the time inside the MSW (T) for low- and high-dose (200 or 500 mg bid) clarithromycin that were 6 and 0 h, 24 and 4 h, 15 and 2 h, 5 and 17 h for the strains with MICs (mg/L) of 0.016, 0.031, 0.062-0.125, and 0.25, respectively.
This study showed that in the clarithromycin-sensitive clinical isolates of H. pylori, low-dose clarithromycin may lead to decreased drug sensitivity or even clarithromycin resistance; strains with a 0.25 mg/L MIC display a high risk of treatment failure.
克拉霉素耐药性在幽门螺杆菌（H. pylori）的治疗中成为一个全球健康关注问题。突变预防浓度（MPC）代表了抗菌药物选择耐药突变体的倾向。最低抑菌浓度（MIC）和 MPC 之间的浓度范围定义为突变选择窗（MSW）。在这项研究中，我们旨在通过研究 H. pylori 临床分离株的 MSW 来确定克拉霉素耐药性增加的原因。
从一项双盲试验中选择了一个包含 68 株克拉霉素敏感的 H. pylori 菌株的回顾性亚组。使用琼脂平板测定法测定 MIC 和 MPC。使用 Sanger 测序进行基因测试。所有分离株均为野生型，33.82%（23/68）的 MIC 为 0.016mg/L，45.59%（31/68）的 MIC 为 0.031mg/L，16.18%（11/68）的 MIC 为 0.062mg/L ≤MIC ≤0.125mg/L，4.41%（3/68）的 MIC 为 0.25mg/L。分离株的 MPC（mg/L）分别为：0.062/0.125、0.125/0.5、0.25/0.25 和 1/2。MPC 与 MIC 呈中度相关（r=0.65，P<0.0001）。使用已发表的数据和 MPC，我们计算了低剂量（200 或 500mg bid）和高剂量（200 或 500mg bid）克拉霉素在 MIC（mg/L）分别为 0.016、0.031、0.062-0.125 和 0.25 的菌株中处于 MSW 内的时间（T），分别为 6 和 0 小时、24 和 4 小时、15 和 2 小时、5 和 17 小时。
本研究表明，在克拉霉素敏感的 H. pylori 临床分离株中，低剂量克拉霉素可能导致药物敏感性降低甚至克拉霉素耐药；MIC 为 0.25mg/L 的菌株治疗失败的风险较高。
