The Primary Resistance of Helicobacter pylori in Taiwan after the National Policy to Restrict Antibiotic Consumption and Its Relation to Virulence Factors-A Nationwide Study.
OBJECTIVE
The Taiwan Government issued a policy to restrict antimicrobial usage since 2001. We aimed to assess the changes in the antibiotic consumption and the primary resistance of H. pylori after this policy and the impact of virulence factors on resistance.


METHODS
The defined daily dose (DDD) of antibiotics was analyzed using the Taiwan National Health Insurance (NHI) research database. H. pylori strains isolated from treatment naïve (N=1395) and failure from prior eradication therapies (N=360) from 9 hospitals between 2000 and 2012 were used for analysis. The minimum inhibitory concentration was determined by agar dilution test. Genotyping for CagA and VacA was determined by PCR method.


RESULTS
The DDD per 1000 persons per day of macrolides reduced from 1.12 in 1997 to 0.19 in 2008, whereas that of fluoroquinolones increased from 0.12 in 1997 to 0.35 in 2008. The primary resistance of amoxicillin, clarithromycin, metronidazole, and tetracycline remained as low as 2.2%, 7.9%, 23.7%, and 1.9% respectively. However, the primary levofloxacin resistance rose from 4.9% in 2000-2007 to 8.3% in 2008-2010 and 13.4% in 2011-2012 (p=0.001). The primary resistance of metronidazole was higher in females than males (33.1% vs. 18.8%, p<0.001), which was probably attributed to the higher consumption of nitroimidazole. Neither CagA nor VacA was associated with antibiotic resistance.


CONCLUSIONS
The low primary clarithromycin and metronidazole resistance of H. pylori in Taiwan might be attributed to the reduced consumption of macrolides and nitroimidazole after the national policy to restrict antimicrobial usage. Yet, further strategies are needed to restrict the consumption of fluoroquinolones in the face of rising levofloxacin resistance.
Departments of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan.
Jyh-Ming
JM
Liou
Department of Internal Medicine, E- DA Hospital and I-Shou University, Kaohsiung County, Taiwan.
Chi-Yang
CY
Chang
Departments of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan.
Mei-Jyh
MJ
Chen
Departments of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan.
Chieh-Chang
CC
Chen
Departments of Internal Medicine, National Taiwan University Hospital, Yun-Lin Branch, National Taiwan University College of Medicine, Yun-Lin, Taiwan.
Yu-Jen
YJ
Fang
Departments of Internal Medicine, National Taiwan University Hospital, Yun-Lin Branch, National Taiwan University College of Medicine, Yun-Lin, Taiwan.
Ji-Yuh
JY
Lee
Department of Internal Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
Jeng-Yih
JY
Wu
Department of Medicine, National Yang-Ming University, School of Medicine, and Taipei Veterans General Hospital, Taipei, Taiwan.
Jiing-Chyuan
JC
Luo
Division of Gastroenterology, Department of Internal Medicine, Mackay Memorial Hospital, Taipei, Taiwan.
Tai-Cherng
TC
Liou
Division of Gastroenterology, Department of Internal Medicine, Mackay Memorial Hospital, Taipei, Taiwan.
Wen-Hsiung
WH
Chang
Department of Internal Medicine, E- DA Hospital and I-Shou University, Kaohsiung County, Taiwan.
Cheng-Hao
CH
Tseng
Division of Gastroenterology, Taichung Veterans General Hospital, Taichung, Taiwan, and Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan.
Chun-Ying
CY
Wu
Departments of Internal Medicine, National Taiwan University Hospital, Yun-Lin Branch, National Taiwan University College of Medicine, Yun-Lin, Taiwan.
Tsung-Hua
TH
Yang
Department of Internal Medicine, Taipei Medical University Hospital, Taipei, Taiwan.
Chun-Chao
CC
Chang
Departments of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan.
Hsiu-Po
HP
Wang
Institute of Clinical Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
Bor-Shyang
BS
Sheu
School of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan.
Jaw-Town
JT
Lin
Division of Gastroenterology, Department of Internal Medicine, Mackay Memorial Hospital, Taitung Branch, Taitung, Taiwan, and Department of Nursing, Meiho University, Pingtung, Taiwan.
Ming-Jong
MJ
Bair
Departments of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan.
Ming-Shiang
MS
Wu
D000658:Amoxicillin / Q000494:pharmacology / Q000627:therapeutic use; D000900:Anti-Bacterial Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D017291:Clarithromycin / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D005838:Genotype; D016481:Helicobacter Infections / Q000188:drug therapy*; D016480:Helicobacter pylori / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development*; D006801:Humans; D008297:Male; D008795:Metronidazole / Q000494:pharmacology / Q000627:therapeutic use; D013624:Taiwan; D013752:Tetracycline / Q000494:pharmacology / Q000627:therapeutic use; D037521:Virulence Factors
D000900:Anti-Bacterial Agents; D037521:Virulence Factors; D008795:Metronidazole; D000658:Amoxicillin; D013752:Tetracycline; D017291:Clarithromycin