PMID- 18416582
OWN - NLM
STAT- MEDLINE
DCOM- 20080909
LR  - 20211020
IS  - 0012-6667 (Print)
IS  - 0012-6667 (Linking)
VI  - 68
IP  - 6
DP  - 2008
TI  - Therapy for Helicobacter pylori infection can be improved: sequential therapy and 
      beyond.
PG  - 725-36
AB  - As with other bacterial infections, successful treatment of Helicobacter pylori 
      infections depends on the use of antibacterial agents to which the organism is 
      susceptible. In this article, we use the proposed report card grading scheme 
      (i.e. grade A, B, C, D, F) for the outcome of clinical trials, where 
      intention-to-treat cure rates >95% = A, 90-95% = B, 85-89% = C, 81-84% = D and 
      <81% = F. The goal of therapy is to consistently cure >95% of patients (e.g. 
      provide grade A results). Like tuberculosis, H. pylori infections are difficult 
      to cure and successful treatment generally requires the administration of several 
      antibacterial agents simultaneously. Duration of therapy is also important and 
      depends upon whether resistance is present; 14 days is often best. With few 
      exceptions, worldwide increasing macrolide resistance now undermines the 
      effectiveness of the legacy triple therapy (e.g. a proton pump inhibitor [PPI], 
      clarithromycin and amoxicillin) and, in most areas, cure rates have declined to 
      unacceptable levels (e.g. grade F). The development of sequential therapy was one 
      response to this problem. Sequential therapy has repeatedly been shown in 
      head-to-head studies to be superior to legacy triple therapy. Sequential therapy, 
      as originally described, is the sequential administration of a dual therapy (a 
      PPI plus amoxicillin) followed by a Bazzoli-type triple therapy (a PPI plus 
      clarithromycin and tinidazole) and has been shown to be especially useful where 
      there is clarithromycin resistance. However, the cure rates of the original 
      sequential treatment are grade B and can probably be further improved by changes 
      in dose, duration or administration, such as by continuing the amoxicillin into 
      the triple therapy arm. The sequential approach may also be more complicated than 
      necessary, based on the fact that the same four drugs have also been given 
      concomitantly (at least nine publications with >700 patients) as a quadruple 
      therapy with excellent success. This article discusses the approach to therapy in 
      the modern era where antimicrobial resistance is an increasing problem and legacy 
      triple therapy is no longer an acceptable initial choice. Methods to achieve 
      acceptable eradication rates (e.g. grade A or B results) are discussed and, 
      specifically, sequential therapy is considered both conceptually and practically. 
      Suggestions are provided regarding how sequential therapy might be improved to 
      become a grade A therapy as well as how to identify situations where it can be 
      expected to yield unacceptable results. New uses for current drugs are discussed 
      and suggestions for subsequent randomized comparisons to overcome phenotypic and 
      genotypic resistance are given. We propose a change in focus from comparative 
      studies (designed to prove that a new therapy is superior to a known inferior 
      therapy) to demanding that efficacious therapies meet or exceed a pre-specified 
      level of success (i.e. grade A or B result). To do so, coupled with less concern 
      about the effect of recommendations on the pharmaceutical industry, should 
      provide clinicians with much higher quality information, and improve the quality 
      of medical care and recommendations regarding treatment. Ultimately, there is 
      little or no justification for comparative testing that includes an arm with 
      known unacceptably low results. H. pylori gastritis is an infectious disease and 
      should be approached and treated as such.
FAU - Graham, David Y
AU  - Graham DY
AD  - Department of Medicine, Michael E. DeBakey Veterans Affairs Medical Center, 
      Houston, Texas 77030, USA. dgraham@bcm.tmc.edu
FAU - Lu, Hong
AU  - Lu H
FAU - Yamaoka, Yoshio
AU  - Yamaoka Y
LA  - eng
GR  - DK56338/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - New Zealand
TA  - Drugs
JT  - Drugs
JID - 7600076
RN  - 0 (Anti-Bacterial Agents)
RN  - 0 (Proton Pump Inhibitors)
SB  - IM
MH  - Anti-Bacterial Agents/*administration & dosage/economics
MH  - Clinical Trials as Topic
MH  - Cost-Benefit Analysis
MH  - Drug Administration Schedule
MH  - Drug Costs
MH  - Drug Resistance, Bacterial
MH  - Drug Therapy, Combination
MH  - Helicobacter Infections/*drug therapy/microbiology
MH  - *Helicobacter pylori
MH  - Humans
MH  - Practice Guidelines as Topic
MH  - Proton Pump Inhibitors/*administration & dosage/economics
MH  - Research Design
MH  - Treatment Outcome
EDAT- 2008/04/18 09:00
MHDA- 2008/09/10 09:00
CRDT- 2008/04/18 09:00
PHST- 2008/04/18 09:00 [pubmed]
PHST- 2008/09/10 09:00 [medline]
PHST- 2008/04/18 09:00 [entrez]
AID - 6861 [pii]
AID - 10.2165/00003495-200868060-00001 [doi]
PST - ppublish
SO  - Drugs. 2008;68(6):725-36. doi: 10.2165/00003495-200868060-00001.