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Volume 48, Number 1, February 2015

Comparative in vitro antimicrobial susceptibility and synergistic activity of antimicrobial combinations against Helicobacter pylori isolates in Taiwan 

Aristine Cheng, Wang-Huei Sheng, Jyh-Ming Liou, Hsiu-Po Wang, Ming-Shiang Wu, Jaw-Town Lin, Shan-Chwen Chang

Received: April 30, 2012    Revised: June 3, 2012    Accepted: July 12, 2012   


Corresponding author:

* Corresponding author. Division of Infectious Diseases, Department of Internal Medicine, National Taiwan University Hospital, No. 7,
Chung-Shan South Road, Taipei 100, Taiwan.
E-mail address: (W.-H. Sheng). 


Background and purpose: 

Antimicrobial resistance is a major determinant of Helicobacter pylori treatment failures. We conducted a population-based survey to monitor changing antimicrobial susceptibility of H. pylori isolates in Taiwan, with a focus on combinatorial effects of synergism and the influence of acidity. 



H. pylori isolates from endoscopic specimens taken from patients enrolled at two medical centers were obtained between January 2008 and December 2009. Minimum inhibitory concentrations (MICs) were determined by agar dilution and Etest methods. Agar media of varying pH (pH 7.3, 6.0, or 5.0) were used to assess whether acidity influences the bactericidal effects of the agents tested. Time-kill assays were used to assess for synergism between different drug combinations. 



A total of 176 non-duplicate H. pylori isolates from endoscopic specimens were tested. The following MIC90 (mg/L) (susceptible) results were obtained at neutral pH 7.3: amoxicillin, 0.25 (100%); tetracycline, 0.5 (100%); metronidazole, 32 (67.6%); clarithromycin, 0.25 (90.3%); ciprofloxacin, 1 (92.0%); gemifloxacin, 0.5 (94.9%); levofloxacin, 1 (93.2%); and moxifloxacin, 1 (91.5%). A decrease in pH from 6.0 to 5.0 significantly decreased the antimicrobial activity of levofloxacin and moxifloxacin against H. pylori. For clarithromycin-susceptible isolates, levofloxacin combined with clarithromycin provided both synergistic and bactericidal effects. For clarithromycin-resistant isolates with amoxicillin hypersusceptibility (MIC <0.01 mg/L), levofloxacin with amoxicillin or minocycline had at best additive effect but no bactericidal effects. 



Amoxicillin, tetracycline, clarithromycin, and fluoroquinolones, but not metronidazole, showed good in vitro anti-H. pylori activity (>90% susceptible). Synergism was only observed for clarithromycin-susceptible isolates. Acidity adversely influenced the antimicrobial activity of levofloxacin against H. pylori. 


Key words:

Acidity, Antibiotic combination, Antimicrobial activity, Helicobacter pylori, Microbial susceptibility, Minimum inhibitory concentration