Management of Helicobacter pylori infection
BMJ 2001; 323 doi: https://doi.org/10.1136/bmj.323.7320.1047 (Published 03 November 2001) Cite this as: BMJ 2001;323:1047All rapid responses
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Dear Sir,
after reading the brief, but comprehensive review by Harris and Misiewicz
(1), I noticed that Authors seem not to take into account the evidence
coming from a recent Japanese large-scale prospective, randomized
study.(2) Uemira et al., studying dyspeptic patients for 7.8 years mean
follow-up, found incidence of gastric cancer in almost 3 percent of the
H.pylori infected versus none in the non-infected. High cancer incidence
was found, when subgrouping, even in patients with nonulcer dyspepsia, for
whom eradication has remained until now an unsolved issue.
From these
results, the role of H.pylori as a gastric carcinogen seems undeniable now
more than ever.I wonder if the Authors will be willing to change the
approach to the controversy, and if giving raise to campaign of testing
(and treating) H.pylori on a population basis, even in absence of
megatrials, is our next (best) thing.
1. Harris A, Misiewicz JJ. ABC of the upper gastrointestinal tract:
Management of Helicobacter pylori infection. BMJ 2001;323:1042-1046
2. Uemura N, Okamoto S, Yamamoto S, Matsumura N, Yamaguchi S,
Yamakido M, Taniyama K, Sasaki N, Schlemper RJ. Helicobacter pylori
Infection and the Development of Gastric Cancer. N Engl J Med 2001;345:784
-789
Competing interests: No competing interests
Editor- I enjoyed Harris and Misiewicz’s paper on management of H.
pylori infection(1). They are congratulated for taking a balanced view of
the contentious issues surrounding treatment in non-ulcer patients.
However, several inconsistencies are apparent in their approach to ulcer
patients, for whom solid evidence for treatment is available.
The authors advocate only two attempts at eradication in duodenal and
gastric ulcer patients: failure of the second being followed by
maintenance anti-secretory therapy. Although the 90% success rate for one
course of eradication therapy is ideal, as quoted by the authors, combined
data from randomised controlled trials suggest eradication rates of 73-87%
are more usual(2). In everyday practice, without trialist enthusiasm,
rates of 64% or lower may be expected, depending on the regimen and
interest of the clinician(3). Thus after two courses of therapy,
potentially 1 in 8 patients may still be infected and failure to persevere
with eradication denies these patients a treatment that alters the natural
history of the disease by preventing ulcer recurrence and haemorrhage.
Continuous anti-secretory therapy is less convenient, less effective and
more costly, thus strategies must be constructed to improve overall
eradication rates.
In the light of this need to optimise success, the authors’ bias
towards proton pump inhibitor (PPI)-based therapies and obvious reluctance
to endorse ranitidine bismuth citrate (RBC)is surprising. RBC-based triple
therapies are at least equivalent to, and in some cases significantly
superior to PPI-based regimens as initial therapy(2). Bismuth-based
regimens (either RBC or colloidal bismuth) appear superior to others
following an initial failure(3,4). In this situation, RBC-tetracycline-
metronidazole triple therapy produced significantly better eradication
rates than the PPI-bismuth quadruple therapy advocated by the authors(5).
RBC-based therapies are effective and equivalent in cost to PPI-therapies,
it is unfortunate that the authors did not recommend their wider use.
There are relatively few data concerning 3rd line therapies. After
using both clarithromycin-, and nitroimidazole-containing regimes, there
is no logical combination. Although a PPI-rifabutin-amoxicillin
combination regimen appears promising in this situation, therapy directed
by endoscopy, culture and sensitivity testing seems better than empirical
choice(3). Using a 3-step algorithm >98% of patients requiring H.
pylori eradication can be successfully treated, removing the need for
continued drug therapy(3).
It is important that strategies for H. pylori eradication are not
based merely on first-line eradication rates but include appropriate
further steps to maximise success in those who will definitely benefit
from therapy.
References
1 Harris A, Misiewicz JJ. Management of Helicobacter pylori
infection. BMJ 2001;323:1047-1050.
2 Gisbert JP, Gonzalez L, Calvet X, Roque M, Gabriel R, Pajares JM.
Helicobacter pylori eradication: proton pump inhibitor vs. ranitidine
bismuth citrate plus two antibiotics for 1 week-a meta-analysis of
efficacy. Aliment Pharmacol Ther 2000;14:1141-50.
3 Beales IL. Efficacy of Helicobacter pylori eradication therapies:
a single centre observational study. BMC Gastroenterol 2001;1:7
4 Kearney DJ. Retreatment of Helicobacter pylori infection after
initial treatment failure. Am J Gastroenterol 2001;96:1335-9.
5 Gisbert JP, Gisbert JL, Marcos S, Gravalos RG, Carpio D, Pajares
JM. Seven-day 'rescue' therapy after Helicobacter pylori treatment
failure: omeprazole, bismuth, tetracycline and metronidazole vs.
ranitidine bismuth citrate, tetracycline and metronidazole. Aliment
Pharmacol Ther 1999;13:1311-1316.
Competing Interests
Dr Beales has received research funding from AstraZeneca and financial
support and sponsorship for educational activities from AstraZeneca,
Jannssen-Cilag and Wyeth. Dr Beales has investments in a number of unit
trusts which have holdings in a number of pharmaceutical companies
including AstraZeneca and GlaxoSmithKline.
Competing interests: No competing interests
To the editor,
Helicobacter pylori (HP) infection is very prevalent worldwide and
triple drug schemes have been shown to be the most effective approach to
erradicate HP infection.
Nevertheless, high rates of resistance against some antibiotics as
well as high costs affect the effectiveness of these therapies.(1)
The Latin-American Consensus Conference on Helicobacter pylori
infection (2) suggest the use of furazolidone, an old but cheap
antibiotic, as a good alternative to metronidazole in triple therapy for
Helicobacter pylori eradication in areas where metronidazole resistant
bacteria are common.
We report a cost-effective alternative for the therapy of HP
infection in low income populations with a high prevalence of infection
with this bacteria.
In a prospective, open, simple blind study De Idiaquez et al (3)
included 59 peruvians patients with diagnosis
of HP infection. They received the following scheme for 10 days:
tetracycline 500 mg qid., furazolidone 100 mg qid.,
and colloidal bismuth subcitrate 120 mg qid.
HP erradication was achieved in 54 patients (91.5%). Control biopsies
showed improvement in the following parameters: presence and density of
HP (p<_0.001 presence="presence" depth="depth" and="and" grade="grade" of="of" chronic="chronic" gastritis="gastritis" p0.001="p0.001" inflammatory="inflammatory" activity="activity" extent="extent" mucinous="mucinous" damage="damage" lymphoid="lymphoid" follicles="follicles" p0.001.="p0.001." p="p"/> Also in Peru Ramirez-Ramos A et al (4) in a study involved three
randomized trials show that furazolidone combined with bismuth
subsalicylate and amoxicillin, erradicated infection in 82% of patients.
Another authors as Segura et al (5) evaluate the combination of
subcitrate 240 mg b.d.,
furazolidone 100 mg q.d.s. and amoxycillin 500 mg
q.d.s. for 14 days in 30 patients for the treatment of H. pylori infection
in Colombia. 25 patients were cured (86%, 95% CI: 65-94%). Mild, well-
tolerated side-effects were reported by six patients (20%).
This evidence suggest furazolidone-containing therapies may become
especially useful in developing countries as an
effective, simple and inexpensive non-metronidazole
therapy for H. pylori infection.
Walter H. Curioso, medical student
Universidad Peruana Cayetano Heredia, Apartado 4314, Lima-100, Peru
E-
mail: 03892@upch.edu.pe
Walter I. Curioso, MD., Chief of gastrointestrinal endoscopy
Hospital Alberto Sabogal Sologuren, Callao, Peru
References
1) Harris A, Misiewicz JJ. Management of Helicobacter pylori
infection. BMJ. 2001 Nov 3;323(7320):1047-1050.
2) Coelho LG, Leon-Barua R, Quigley EM. Latin-American Consensus
Conference on Helicobacter pylori infection. Latin-American National
Gastroenterological Societies affiliated with the Inter-American
Association of Gastroenterology (AIGE). Am J Gastroenterol. 2000
Oct;95(10):2688-91.
3) De ldiáquez D, Bussalleu A, Rodrigo I, et al.
Erradicación de la infección por Helicobacter pylori utilizando
Tetraciclina, Furazolidona y Bismuto en pacientes dispépticos con y sin
úlcera péptica.
Rev Gastroenterol Peru 1999;19(3):179-94. Full-text available (in
spanish):
http://200.10.68.58/bibvirtual/revistas/gastro/vol_19n3/trabajos01.htm
4) Ramirez-Ramos A, Gilman RH, Leon-Barua R, et al.
Rapid recurrence of Helicobacter pylori infection in
Peruvian patients after successful eradication.
Clin Infect Dis 1997 Nov;25(5):1027-31
5) Segura AM, Gutierrez O, Otero W, et al.
Furazolidone, amoxycillin, bismuth triple therapy for
Helicobacter pylori infection. Aliment Pharmacol Ther 1997 Jun;11(3):529-
32
Competing interests: No competing interests
Dear Sirs,
Having followed and enjoyed your G.I. series with great interest, I
was rather alarmed to find an incorrect drug dosage ten times higher than
the intended amount which is stated in the final table of your article,
surely this should be Omeprazole 40mgs. once daily rather than Omeprazole
400mgs!
Whilst it may be an obvious typing error it may lead to a grave
clinical error occuring.
Competing interests: No competing interests
Editor-We read with great interest the excellent clinical review
article by Harris and Misiewicz (3 November issue) concerning the
management of Helicobacter pylori infection (1).
Nevertheless, in our opinion, a great question we would underline is
whether to treat the majority of infected individuals when they are
asymptomatic. Some literature data suggest that chronic diseases may have
an infectious component (2). For example, even is contradictory, several
lines of research indicate that common chronic infections (including
cytomegalovirus, herpesviruses, Chlamydia pneumoniae, dental infections,
and ultimately Helicobacter pylori) are plausible candidate for triggering
and perpetuating inflammatory changes that may contribute to the
development of atherosclerosis through the generation of a persistent low-
grade inflammatory stimulus. Now, the discovery that transmissible agents
may play roles in diseases non suspected of being infectious in origin may
have important implications for treatment. There is a simple strategy that
states: testing an infection in the individual patient for any reason and
with any method should always be followed up with treatment. Therefore, in
our opinion, the major priority in the future could become not whom to
treat but rather whom to test.
Giovanni Cammarota, MD, Investigator
Massimo Montalto, MD, Fellow of Internal Medicine
Giovanni GAsbarrini, MD, Director, Professor of Internal Medicine
References.
1. Harris A, Misiewicz JJ. BMJ 2001;323:1047-1050.
2. Libby P, Egan D, Skarlatos S. Roles of infectious agents in
atherosclerosis and restenosis: an assessment of the evidence and need for
future research. Circulation 1997;96:4095-103.
Competing interests: No competing interests
I was a little surprised to see no mention at all, in this review
paper on management of H.
pylori infection, of the potential reservoir of H. pylori in dental plaque
on teeth. Because
this is a biofilm, no antibiotic will penetrate it and if it carries the
organism, it is essential
to remove it mechanically with oral hygiene, scaling and root planing,
exactly as for
periodontal diseases caused by plaque microorganisms (1).
The effect of removal and control of dental plaque on the plaque
reservoir of H. pylori
was shown clearly in a short study published this year (2). Triple
therapy alone
(omeprazole, clarithromycin + metronidazole) was wholly ineffective, but
scaling
followed by chlorhexidine mouthrinse eradicated H. pylori in 80-90% of
patients.
Everyone dealing with bacterial diseases should remember that if biofilms
are involved,
antibiotics alone are unlikely to be sufficient treatment. Similarly, the
mouthrinse is
useless without the scaling.
Biofilms like dental plaque provide a ready source for re-infection.
They are complex
communities of many bacterial species with powerful defences against
chemical and
pharmacological threats (3), but some organisms may not gain a foothold in
them because
of bacterial antagonisms. This means that not all patients with H. pylori
infection will
necessarily have the organism in their dental plaque, which may have
misled some
investigators in the past. Re-infection from plaque will also be subject
to variable host
defences, and therefore not occur consistently in all cases where
conventional H. pylori
therapy is used.
1. Watts TLP. Periodontitis for medical practitioners. BMJ 1998;
316: 993-996.
2. Butt AK, Khan AA, Suleman BA, Bedi R. Randomized clinical trial
of Helicobacter
pylori from dental plaque. Br J Surg 2001; 88: 206.
3. Watts TLP. Periodontics in Practice. London: Martin Dunitz,
2000, p 47-52.
Competing interests: No competing interests
Dear Dr. Adam Harris and Dr. J J Misiewicz,
concerning your excellent clinical review article "Management of
Helicobacter pylori infection" in BMJ 2001;323:1047-1050, I wonder about
the high dose of omeprazole of 400 mg/daily for eradication therapy of H.
pylori on page 1050, flow sheet for choosing a treatment regimen for H
pylori eradication. Do you recommend such a high doses or should it be 40
mg/daily?
Sincerely yours,
B. Vogt, MD
Nephrology/Hypertension,
Inselspital,
3010 Berne,
Switzerland
Competing interests: No competing interests
H pylori eradication therapy in patients undergoing endoscopy can be individually tailored
Helicobacter pylori eradication therapy in patients undergoing
endoscopy can be individually tailored to avoid resistance and treatment
failure.
Editor--In their review on the management of Helicobacter pylori
infection Harris and Misiewicz1 suggest that patients "likely" to have
metronidazole resistant H pylori infection should be treated with non-
nitroimidazole containing eradication regimens. However, prediction of
resistance to antimicrobials in H pylori infection relies on the
availability of resistance data in the given geographic area of practice.
Few hospitals carry out sensitivity testing of H pylori therefore local
data is seldom available. In addition, although the authors rightly point
out that metronidazole resistance is commoner in women and patients from
developing countries, translation of this knowledge into prescribing
practice is difficult in the treatment of individual patients.
Our study of 1064 consecutive patients in Sheffield found to be H
pylori culture-positive at endoscopy showed metronidazole resistance rates
to be 45% for women compared to 37% for men (odds ratio 1.48; 95%
confidence interval 1.15-1.91) and for patients 60 years or over
resistance was 34% compared to 44% for patients <_60 years="years" or="or" _0.62="_0.62" _95ci="_95ci" _0.48-0.82.="_0.48-0.82." a="a" pragmatic="pragmatic" approach="approach" to="to" h="h" pylori="pylori" eradication="eradication" treatment="treatment" may="may" be="be" exclude="exclude" nitroimidazoles="nitroimidazoles" from="from" regimens.="regimens." in="in" our="our" view="view" this="this" would="would" not="not" advised="advised" as="as" metronidazole="metronidazole" is="is" cheap="cheap" and="and" effective="effective" antibiotic="antibiotic" when="when" used="used" regimes="regimes" treat="treat" sensitive="sensitive" strains.="strains." also="also" increased="increased" use="use" of="of" clarithromycin="clarithromycin" replacement="replacement" for="for" likely="likely" result="result" significantly="significantly" more="more" disruption="disruption" induction="induction" resistance="resistance" host="host" microflora3="microflora3" thereby="thereby" reduce="reduce" the="the" efficacy="efficacy" macrolides="macrolides" other="other" infectious="infectious" conditions.="conditions." p="p"/> Culture and sensitivity testing of H pylori is well established and
requires few special facilities. As the authors discuss management of H
pylori following endoscopy, it would seem appropriate to recommend taking
an additional biopsy at the time of procedure for microbiological culture.
The patients could be treated with proton pump inhibitors, if indicated,
while sensitivity results are obtained (approximately one week) and then
prescribed a specific, effective eradication regime. In this era of
increasing resistance to antimicrobials optimisation of therapy is of
paramount importance in our clinical practice.
Helena K Parsons
research fellow in infection and immunity
h.k.parsons@shef.ac.uk
David S Sanders
research fellow in gastroenterology
Martyn J Carter
specialist registrar in gastroenterology
Alan J Lobo
consultant gastroenterologist
Gastroenterology and Liver Unit,
Royal Hallamshire Hospital,
Sheffield S10 2JF
1 Harris A, Misiewicz JJ. Management of Helicobacter pylori
infection. BMJ 2001; 323: 1047-1050.
2 Parsons HK, Carter MJ, Sanders DS, Winstanley T, Lobo AJ. Rates of
Helicobacter pylori antimicrobial resistance in the United Kingdom and the
effect of age, sex and socio-economic status. Aliment Pharmacol Ther 2001;
3 Adamsson I, Nord CE, Ludquist P, et al. Comparative effects of
omeprazole, amoxycillin plus metronidazole versus omeprazole,
clarithromycin plus metronidazole on the oral, gastric and intestinal
microflora of Helicobacter pylori-infected patients. J Antimicrob
Chemother 1999; 44: 629-40.
Competing interests: No competing interests