Abstract
BackgroundClarithromycin-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.ResultsA 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 MPC50/90 (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 (rs = 0.65, P < 0.0001). Using published data and MPC90, we calculated the time inside the MSW (TMSW) 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.ConclusionsThis 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.
Highlights
Clarithromycin-resistance is becoming a global health concern in the treatment of Helicobacter pylori (H. pylori)
Clarithromycin is the most powerful antimicrobial agent used in the treatment of Helicobacter pylori (H. pylori) infection [1], yet it is recognized as a major cause of peptic ulcers [2]
The MIC90 and MPC90 represented the boundaries of the mutant selection window (MSW) [21]
Summary
Clarithromycin-resistance is becoming a global health concern in the treatment of Helicobacter pylori (H. pylori). Clarithromycin is the most powerful antimicrobial agent used in the treatment of Helicobacter pylori (H. pylori) infection [1], yet it is recognized as a major cause of peptic ulcers [2]. Clarithromycin-containing bismuth quadruple therapies are recommended by many international guidelines in the treatment of H. pylori. The eradication rate has been severely reduced with clarithromycin-containing bismuth quadruple therapies [7]. While it is known that a history of prior clarithromycin use can influence the failure rate of standard triple therapies in patients [13], the mechanisms by which it affects the MICs and the reasoning for the skyrocketing increase in resistance to clarithromycin is unknown [1]
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