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Helicobacter pylori
Should Triple Therapy for Helicobacter pylori
Be Abandoned as No Longer Effective?
a report by
Yoshio Yamaoka, MD, PhD,
1
David Y Graham, MD
1
and Hong Lu, MD, PhD
2
1. Department of Medicine, Michael E DeBakey Veterans Affairs Medical Center, and Baylor College of Medicine, Houston;
2. Department of Internal Medicine, Shanghai Jiao Tong University School of Medicine, and Shanghai Institute of Digestive Disease
Helicobacter pylori causes gastric mucosal inflammation and is now Improving Anti-Helicobacter pylori Therapy
recognized as the causative agent in gastric atrophy, peptic ulcer disease, The initial studies of antimicrobial therapy for H. pylori were performed primarily
gastric adenocarcinoma, and primary gastric B-cell lymphoma. H. pylori has in patients with peptic ulcer disease. It turns out that the cure rate of
an unusual history for an infectious disease, as the majority of the clinical antimicrobial therapy is the highest in that group and lower in patients without
studies to identify effective therapies were performed by gastroenterologists ulcer disease.
11,24,28,29
Initially, the duration of most therapies was
and not by members of the infectious disease community. The requirement 14 days. Although a truly successful therapy had not yet been identified,
that the US Food and Drug Administration (FDA) provide a ‘level playing pharmaceutical companies pushed for shorter duration to achieve marketing
field’ may also be responsible for the current confusion regarding what is advantages. Over time seven days became the recommended duration despite
the best therapy. Part of the confusion is that eradication rates in most the evidence that shorter duration was associated with a reduction, in many
clinical trials are given with little regard to the prevalence of antimicrobial countries, in effectiveness (estimated to be between 9 and 17%, with an
resistance in the population studied. Few would expect comparative studies average of about 12%),
30
as marketing advantage clearly trumped effectiveness
of antibiotics in urinary tract, skin, or pulmonary infections to even include as the primary outcome variable. Shorter duration was sometimes presented as
patients who harbored bacteria resistant to the drugs being tested and then a cost-effectiveness concern,
31
setting aside the true goal of therapy, i.e. to cure
to include them in the overall outcome, yet this is the standard for most the infection. Cost-effectiveness should first be based on achieving a target
reports regarding H. pylori. cure rate and the true cost is the cost of failure to achieve that goal. Failed
therapy results in the patient remaining exposed to the risks of the infection and
As a general rule, the goal of treatment of an infectious disease is to cure its outcomes of gastric atrophy, peptic ulcer, gastric cancer, and transmission to
100% of infections. After a near 100% effective regime is identified, others. Failure should also require re-testing and re-treating, as well as additional
attempts may then be made to simplify the protocol via alternations in follow-ups and all their attendant costs. Typically, these real costs are not
dose, formulation, number or timing of drug administrations, duration of
therapy, etc. Anti-H. pylori therapy has been largely driven by marketing
concerns, particularly in relation to duration of therapy. Large studies of
Yoshio Yamaoka, MD, PhD, is an Associate Professor of
Medicine-Gastroenterology at Baylor College of Medicine, and
dose, duration, formulation, and timing of drug administration are rare,
Director of the Molecular Pathogenesis Laboratory in the
and these topics have not been approached systematically. Worldwide, Digestive Disease Division at the Michael E DeBakey Veterans
the most commonly recommended therapy has been triple therapy
Affairs Medical Center in Houston, Texas. He is the recipient of
research grant support from the National Institutes of Health
consisting of a proton pump inhibitor (PPI), amoxicillin, and clarithromycin
(NIH). Dr Yamaoka is on the Editorial Board of the World Journal
(or metronidazole/tinidazole). of Gastroenterology.
Since 1989, a successful therapy has been defined as one that cures more
David Y Graham, MD, is a Professor in the Departments of
than 80% of patients.
1
By 1995, it seemed that 90% was achievable,
2
and Medicine and Molecular Virology and Microbiology at Baylor
there was hope for 95%. In 2001, Hopkins suggested raising the bar to
College of Medicine in Houston, and also Chief of the Digestive
Disease Section at Baylor College of Medicine and the Michael E
90% intention to treat (ITT) and to 95% with susceptible organisms.
3
The
DeBakey Veterans Affairs Medical Center in Houston. He is a
initial Maastricht consensus conference defined a useful therapy as one Past President of the American College of Gastroenterology
with a cure rate of >80% ITT. This seemingly low hurdle has remained the
(ACG). Dr Graham is the Editor of Helicobacter and the author of
more than 700 scientific papers and several books.
standard through subsequent consensus conferences.
4
In reality, ITT
outcome is a more realistic standard than per protocol in H. pylori
infections considering that pre-treatment susceptibility testing is rarely
Hong Lu, MD, PhD, is an Associate Professor of Medicine in the
Department of Internal Medicine, Shanghai Jiao Tong University
available. While achieving an 80% ITT success rate is a low target,
School of Medicine and the Shanghai Institute of Digestive
increasing resistance and shorter therapy duration have led to the Disease. She is a recipient of the Chinese National Natural
effectiveness of a PPI plus amoxicillin and clarithromycin triple therapy to
Science Fund and a Councillor in the Executive Committee of
young investigators of the Chinese Society of Gastroenterology.
generally fall below that threshold for acceptability in the US and Europe
Dr Lu’s research focuses on the pathogenesis and treatment of
(see Table 1).
5–27
Here, it is proposed that it should be abandoned except Helicobacter pylori-related gastrointestinal diseases.
for in countries with low rates of clarithromycin-resistant H. pylori or for
patients with known susceptible organisms.
© TOUCH BRIEFINGS 2008
65
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