MIC Levels of Resistance Affect H pylori Eradication

Minimum inhibitory concentration levels of resistance to either clarithromycin or metronidazole may play a role in Helicobacter pylori therapy outcome.

Minimum inhibitory concentration (MIC) levels of resistance to either clarithromycin or metronidazole may play a role in Helicobacter pylori therapy outcome, according to a study recently published in the Journal of Antimicrobial Chemotherapy.

The cure rate of standard eradication regimens for H pylori infection is significantly affected by primary antibiotic resistance of clarithromycin and metronidazole. However, despite the presence of single or combined resistant to these antimicrobial agents, evidence suggests that bacterial eradication is still attainable in a definite percentage of patients. Antibiotic resistance of H pylori is assessed by using Etest, a culture-based method performed on gastric biopsies in clinical practice. According to European Committee on Antimicrobial Susceptibility Testing recommendations, MIC values >0.5 mg/L for clarithromycin and >8 mg/L for metronidazole identified resistant H pylori strains. 

However, MICs for resistant strains of H pylori range widely, >0.5 to 256 mg/L for clarithromycin and 0.8 to 256 mg/L for metronidazole, suggesting that it may be clinically valuable to study whether efficacy of eradication therapy depends on different MIC levels of resistance to certain antibiotics rather than an on/off effect. Therefore, this post hoc analysis evaluated whether the efficacy of H pylori eradication therapy may be affected by various MIC values of clarithromycin and/or metronidazole resistance.

Data were collected from a therapeutic trial that included patients (n=1006) with antibiotic susceptibility testing who received first-line sequential therapy. Antibiotic resistance level was classified according to MIC values into low (MIC from >0.5mg/L to £8mg/L for clarithromycin and 8mg/L to £32 mg/L for metronidazole) and high (MIC >8mg/L to 256 mg/L for clarithromycin and >32mg/Lto 256 mg/L for metronidazole). There were 520 (57.1%) patients with susceptible strains, 136 (13.5%) with clarithromycin-resistant strains, 144 (14.3%) with metronidazole-resistant strains, and 206 (20.5%) with clarithromycin- and metronidazole-resistant strains.

In the presence of dual resistance to both clarithromycin and metronidazole, the cure rate was high when MIC levels were low (92.7%) and the cure rate was reduced only when MIC levels of both antibiotics were high (83.9%). However, the cure rates between patients with single antibiotic-resistant strains, regardless of MIC values, did not differ significantly.

Overall, the study authors concluded that, “our data suggest that MIC levels of resistance to either clarithromycin or metronidazole are a matter for concern in H pylori therapy and that bacterial resistance becomes relevant in vivo when strains with dual clarithromycin and metronidazole resistance have high MIC values of at least one of these antibiotics. These results would encourage further research that might lead to a re-evaluation of current MIC breakpoints.”

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De Francesco V, Zullo A, Fiorini G, Saracino IM, Pavoni M, Vaira D. Role of MIC levels of resistance to clarithromycin and metronidazole in Helicobacter pylori eradication [published online November 26, 2018]. J Antimicrob Chemother. doi: 10.1093/jac/dky469