Current Trends in Acid-

Related Disease (limited to

Peptic Ulcer Disease)
Diagnosis and Treatment
Option

Erwin Budi Cahyono

Department of Internal Medicine
RSI Sultan Agung-Universitas Islam Sultan Agung
 Objectives

• At the end of this program, the participant should be able to

– Define peptic ulcer disease (PUD) and H. pylori (HP)
infection
– List the major causes of PUD and recognize its
multifactorial nature;
– List the clinical symptoms of PUD
– Described the proposed mechanism by which H. pylori is
transmitted
– Discuss the procedures used in the diagnosis of PUD and
H. pylori infection
– Discuss medical management of PUD and H. pylori
infection
– List the complications of PUD
Peptic Ulcer Disease (PUD)
 Definition

A circumscribed ulceration of
the gastrointestinal mucosa
occurring in areas exposed to
acid and pepsin and most often
caused by Helicobacter pylori
infection.
(Uphold & Graham, 2003)
 Peptic Ulcers:
Gastric & Dudodenal
 Definitions

• Peptic Ulcer Disease (PUD):

– refers to a group of disorders characterized by the
development of ulceration that may extend through the
muscularis mucosae of the GI tract

• Gastric Ulcer:
– ulceration through the muscularis mucosae of the lesser
curvature of the stomach

• Duodenal ulcer:
– ulceration through muscularis mucosae of the duodenum
 PUD

• Chronic PUD affects at least 10% of the

population (lifetime prevalence: 8-14%)
• 15 million American adults
• New cases close to 500,000 yearly
• Often associated with H. pylori or NSAID
use
• Now considered a curable disease rather
than a chronic condition
• Deaths due to complications- nearly 15,000
yearly
2005 PUD Guidelines (Univ. of Michigan Health System)
 Characteristics of DU and GU
Duodenal Ulcer Gastric Ulcer
• May present < age 40 • Usually seen in
• Rarely associated with 50-60 year olds
NSAID use • Strong relationship to
• Pain often on empty NSAID use
stomach, better with • Pain usually worse after
food or antacids meals
• H. pylori in 90% to 100% • H. pylori in 70% to 90%
Both
•most common symptom: diffuse epigastric pain
•may be pain free
•may be associated with dyspeptic symptoms
•can lead to bleeding, perforation, or obstruction
 Etiology
• A peptic ulcer is a mucosal break, 3 mm or
greater, that can involve the stomach or
duodenum.
• The most important contributing factors are H
pylori, NSAIDs, acid, and pepsin.
• Additional aggressive factors include smoking,
ethanol, bile acids, aspirin, steroids, and stress.
• Important protective factors are mucus,
bicarbonate, mucosal blood flow, prostaglandins,
hydrophobic layer, and epithelial renewal.
– Increased risk when older than 50 d/t decrease
protection
• When an imbalance occurs, PUD might develop.
PUD: Defensive Mechanisms
 H. pylori Defined

• Helicobacter pylori is a gram-negative

spiral-shaped bacterium that colonizes
the human stomach and is associated
with gastritis and PUD.
 H. pylori Infection:
Incidence and Prevalence1-5

Prevalence: 80-90%
Worldwide

Prevalence:
North America
~ 30%

Annual Incidence
In Developing > 3 per 100 persons
Countries

Annual Incidence
in Industrialized
Countries
0.5 per 100 persons
Mechanisms of Disease

PUD and H. pylori Infections

 Gastric Mucosa

Normal Gastric Damaged Gastric

Mucosa Mucosa
 H. Pylori: Mechanism of Disease

• Organism secretes the enzyme urease

which creates an alkaline environment
around the organism
• Produces mucolytic enzymes, i.e. lipase,
phospholipase, which help degrade mucus
barrier
• Thought to decr. the activity of somatastatin
• Chronic disease increase gastrin
levels=>more acid secreted
 Types of Peptic Ulcers

Antral Ulcer Benign Gastric Ulcer

Images courtesy of C. Mel Wilcox, MD.

Initial Evaluation and Management
of the Patient with Dyspepsia

• Dyspepsia- chronic or recurrent upper

abdominal pain or discomfort
– Frequent symptoms > once per week
– Need to rule out GERD, NSAID-induced, other
possible causes
• Management includes empirical H2RA or PPI
therapy, HP testing and treatment if results
are positive, continued acid suppressant
therapy if patient remains symptomatic

AGA Medical Position Statement: Evaluation of Dyspepsia

(Gastroenterology 2005; 129:1753-1755)
 Etiology of PUD

• “No acid, no ulcer” is a dogma

– Action of acid and pepsin
• Hypersectretory disorders
– e.g. Zollinger-Ellison Syndrome
• Presence of Helicobacter pylori
• Drug induced
– NSAIDs
– Corticosteroids
– Alcohol
• Smoking
 NSAIDs and PUD

• NSAIDs are taken intermittently by

approximately 13 million Americans; 1% of
population daily
• Independent risk factor for ulcers, as is
H. Pylori infection
• NSAID-induced ulcers are often associated
with other risk factors
– advance age
– high NSAID dose
– history of PUD +/or GI bleeds
– certain medications, i.e. prednisone
 NSAIDs and PUD-
Mechanism of Disease
• 3 types of mucosal damage
– superficial damage and erosions
» occurs shortly after drug ingestion, clinically significant
– endoscopic ulcers
» usually symptom free, verified by endoscopy only
– clinical ulcers
» small percentage of patients with endoscopic ulcers
• NSAIDs thought to cause inhibition of mucosal
prostaglandins
• No firm guidelines have been established for
management of NSAID-induced ulcers
 Risk Factors for NSAID-Associated
GI Complications
(from highest to lowest risk)

• Past history of PUD or complicated ulcers High

• Multiple NSAID use

• High-dose NSAID use
• Concomitant use of anticoagulants
• Age > 70 years
• SSRI use (Selective serotonin reuptake inhibitors)
• Corticosteroid use
Dalton S et al. Arch Intern Med. 2003;163:59-64
Gabriel S et al. Ann Intern Med. 1991;115:787-796
Low
Garcia Rodriguez et al. Lancet 1994;343-769-772
Silverstein F et al. Ann Intern Med. 1995;123:241-249
Diagnosing PUD
 Subjective Data

• Pain—”gnawing”, “aching”, or “burning”

– Duodenal ulcers: occurs 1-3 hours after a meal and
may awaken patient from sleep. Pain is relieved by
food, antacids, or vomiting.
– Gastric ulcers: food may exacerbate the pain while
vomiting relieves it.
• Nausea, vomiting, belching, dyspepsia, bloating,
chest discomfort, anorexia, hematemesis, &/or
melena may also occur.
– nausea, vomiting, & weight loss more common with
Gastric ulcers
 Objective Data

• Epigastric tenderness
• Guaic-positive stool resulting from occult blood
loss
• Succussion splash resulting from scaring or
edema due to partial or complete gastric outlet
obstruction
– A succussion splash describes the sound obtained by
shaking an individual who has free fluid and air or gas
in a hollow organ or body cavity.
– Usually elicited to confirm intestinal or pyloric
obstruction.
– Done by gently shaking the abdomen by holding either
side of the pelvis. A positive test occurs when a
 Differential Diagnosis

• Neoplasm of the stomach

• Pancreatitis
• Pancreatic cancer
• Diverticulitis
• Nonulcer dyspepsia (also called functional
dyspepsia)
• Cholecystitis
• Gastritis
• GERD
• MI—not to be missed if having chest pain
 Diagnosis

• Endoscopy (aka EGD or

gastroscopy)- gold
standard
• Biopsy and/or cytology
• Isolation of H. pylori
organism
• Complete drug history to
r/o NSAID-induced ulcers,
other ulcerogenic drugs
• History of smoking, alcohol
use
• Radiographic: Barium
swallow or upper GI series
• Analysis of gastric acid
 Endoscopy a MUST if:

• Anorexia is present
• Dysphagia is present
• GI bleeding (gross or occult)
• New onset symptoms in persons over 55
years of age
• Presence of mass
• Unexplained anemia
• Unexplained weight loss
• Severe vomiting
Clinical Manifestations
Clinical Manifestations of PUD

– No symptoms (asymptomatic)
– Epigastric pain (gnawing, burning, vague
abdominal discomfort) –may be temporarily
relieved by foods or antacids
– Usually occurs between meals or when
stomach is empty
– Often nocturnal pain
– Fullness, bloating, belching (eructation)
 Signs of Complicated PUD

• Signs of anemia or bleeding

• Nausea and vomiting (secondary to
obstruction)
• Penetration or perforation (severe
abdominal pain)
• Weight loss, anorexia (possible signs of
cancer)
 Other Common Factors of PUD

• Long term- persistence or recurrence

over months to years (common in
smokers, non-compliant patients,
patients with alcoholism)
• History of self-medication with
intermittent relief
Managing PUD
Therapeutic Strategies for
Ulcers
Diet Drug Therapy

Goals of Therapy
• Relieve symptoms
• Accelerate ulcer healing
• Reverse present complications
• Prevent ulcer recurrence
• Cure disease

Surgery Remove Causes

 Lifestyle Changes

• Discontinue NSAIDs and use Acetaminophen for

pain control if possible.
• Acid suppression--Antacids
• Smoking cessation
• No dietary restrictions unless certain foods are
associated with problems.
• Alcohol in moderation
– Men under 65: 2 drinks/day
– Men over 65 and all women: 1 drink/day
• Stress reduction
Optimal pHs to Prevent Ulcers

pH Observation
> 3.5 Decreased incidence of stress ulcers
4 Best pH to decrease acid and ulcers
> 4.5 Pepsin is inactivated
~5 99.9% of gastric acid neutralized
6 Best pH to decrease / stop GI bleeding
 Drugs used in the
Management of PUD

• Proton Pump • Antacids

Inhibitors (PPIs) • Sucralfate
• Histamine-2 • Antibiotics
Receptor • Misoprostol - for
Antagonists (H2RAs) PREVENTION of
NSAID-induced
ulcers
 PPIs

 These agents are often the drugs of

choice in the treatment of acid-peptic
disorders: GERD, PUD, and pathologic
gastrointestinal hypersecretory
conditions such as Zollinger-Ellison
Syndrome.
 PPIs

• Block the H+, K+ • Very similar in

ATPase pump, indications with
which inhibits acid minor exceptions
secretion. • The PPIs have
• Currently, IV demonstrated
pantoprazole similar efficacy and
esomeparole or safety data
lansoprazole can be • Generally well
used for in patients tolerated
unable to take the
oral formulation.
Mechanism of Action of the PPIs

Metz D. et al. Clin Gast. and Hepatology 2005:3:1169

 Key Points about the
Pharmacology of the PPIs

• They must be activated first before binding

to the proton pump
• FDT (Fast Disintegrating Tablet)
technology – Lansoprazole – formulations
in order to fast onset of action and prevent
early activation when in contact with
gastric acid BEFORE reaching their
specific site of binding
 Treatment Plan: H. Pylori

• Medications: Triple therapy for 14 days is considered the

treatment of choice.
– Proton Pump Inhibitor + clarithromycin and amoxicillin
» Omeprazole : 20 mg PO bid for 14 d or
Lansoprazole : 30 mg PO bid for 14 d or
Rabeprazole : 20 mg PO bid for 14 d or
Esomeprazole : 40 mg PO qd for 14 d plus
Clarithromycin : 500 mg PO bid for 14 and
Amoxicillin : 1 g PO bid for 14 d
» Can substitute Flagyl 500 mg PO bid for 14 d if allergic to PCN
– In the setting of an active ulcer, continue qd proton pump
inhibitor therapy for additional 2 weeks.
• Goal: complete elimination of H. Pylori. Once achieved
reinfection rates are low. Compliance!
 Treatment Plan: Not H. Pylori

• Medications—treat with Proton Pump

Inhibitors or H2 receptor antagonists to
assist ulcer healing
– H2 receptor antagonists: for up to 8 weeks
– PPI: for 4-8 weeks.
 Prevention
• Consider prophylactic therapy for the following patients:
– Pts with NSAID-induced ulcers who require daily NSAID
therapy
– Pts older than 60 years
– Pts with a history of PUD or a complication such as GI
bleeding
– Pts taking steroids or anticoagulants or patients with
significant comorbid medical illnesses
• Prophylactic regimens that have been shown to dramatically
reduce the risk of NSAID-induced gastric and duodenal
ulcers include the use of a prostaglandin analogue or a
proton pump inhibitor.
– Misoprostol 100-200 mcg PO 4 times per day
– Omeprazole 20-40 mg PO every day
– Lansoprazole 15-30 mg PO every day
 Complications

• Perforation & Penetration—into pancreas,

liver and retroperitoneal space
• Peritonitis
• Bowel obstruction, Gastric outflow
obstruction, & Pyloric stenosis
• Bleeding--occurs in 25% to 33% of cases and
accounts for 25% of ulcer deaths.
• Gastric Carcinoma
 Prognosis/Complications of PUD

• Prognosis
– If adequately diagnosed, reduction or
removal of risk factors, and no
complications- excellent prognosis
• Complications
– Bleeding
– Obstruction
– Penetration or perforation
 Gastric Cancer

• The persistent chronic

inflammation with with
H. pylori increases the risk
of distal gastric
adenocarcinoma.
• It is evident by the results of
numerous studies that there
is a clear correlation
between H. pylori infection
and the risk of gastric
cancer Image courtesy of
C. Mel Wilcox, MD.
 Surgery

• People who do not respond to medication, or

who develop complications:
– Vagotomy - cutting the vagus nerve to interrupt
messages sent from the brain to the stomach to
reducing acid secretion.
– Antrectomy - remove the lower part of the stomach
(antrum), which produces a hormone that stimulates
the stomach to secrete digestive juices. A vagotomy is
usually done in conjunction with an antrectomy.
– Pyloroplasty - the opening into the duodenum and
small intestine (pylorus) are enlarged, enabling
contents to pass more freely from the stomach. May
be performed along with a vagotomy.
Evaluation/Follow-up/Referrals

• H. Pylori Positive: retesting for tx efficacy

» Urea breath test—no sooner than 4 weeks after therapy
to avoid false negative results
» Stool antigen test—an 8 week interval must be allowed
after therapy.
• H. Pylori Negative: evaluate symptoms after one
month. Patients who are controlled should cont.
2-4 more weeks.
• If symptoms persist then refer to specialist for
additional diagnostic testing.
PPIs: Adverse Effects/Precautions

• Generally well tolerated when used short term (< 12

weeks)
– the most common adverse effects are headache, diarrhea,
abdominal pain, and nausea
• Long term (> 12 weeks)
• No evidence that long-term PPIs promote
development of
– gastric adenocarcinoma
– gastric hyperplasia, dysplasia or carcinoids
– atrophic gastritis
– intestinal metaplasia
• No change in serum cobalamin or nutrient absorption
Am Fam Physician 2002;66:273
 PPIs: Metabolism

• All are extensively metabolized by the

CYP450 enzyme system
– 2C19 isoform and CYP3A4 play roles in PPI
biotransformation
• Omeprazole, esomeprazole also inhibit the
CYP isoforms (CYP219 and CYP2C8)
– This has not been found to be of clinical
significance when it comes to potential drug-drug
interactions
 Patients Who are Poor CYP2C19
Metabolizers

• Greater response with PPIs requiring

this enzyme for metabolism:
– All except rabeprazole
• Poor CYP2C19 responders include
patients of Asian descent
• Greatest risk for toxicity appears with
omeprazole and esomeprazole

Ref: Roche V. Am J Pharm Ed. 2006; 70 (5): 101

 Summary Info on the PPIs

• PPIs have become the mainstay in the

treatment of acid-related gastrointestinal
diseases
• Fast Disintegrating Tablet (Lansoprazole)
• PPIs can heal active ulcers even if NSAID is
continued
• PPIs are the most potent antisecretory agents
available
 Summary Info on the PPIs (contd.)

• PPIs lead to more rapid healing and

relief of symptoms than other anti-ulcer
drugs
• Best time to take PPIs would be 30-60
mins. before a meal
• All 5 PPIs are acid-labile and are
formulated as enteric-coated products
 Advantages of
Current PPI therapy

• Superior acid suppression as compared

to H2RAs
• Ease of use (once to twice daily dosing)
• Availability in oral and IV dosage forms
• Proven clinical efficacy for a variety of
acid-related disorders including H. pylori
associated ulcers and NSAID-induced
gastric ulcers
 Limitations of
Current PPI Therapy
• Variability of effect- a proportion of
individuals exhibit mutations to
CYP2C19 (poor metabolizers) 1

• Not optimal in handling nocturnal acid

breakthrough1,2

1. Vakil N. Aliment. Pharmcol. Ther. 2004; 19: 1041-1049

2. 2. Small R. P&T. 2005;30(12):698713
Characteristics of an Ideal PPI:
Meeting Unmet Needs
• Faster onset of action and symptom control1,2
• Sustained 24-hr effect with better nocturnal acid
control2
• Better control of atypical or extra-esophageal
symptoms2
• High oral bioavailability formulations effective in
patients at risk for SRMD in the ICU2
• Liquid dosage form for patients who cannot swallow
intact capsules or tablets1
• Optimal and safe co-therapy with NSAIDs2
• Effective in poor metabolizers an nonresponders2
1. Small R. P&T. 2005;30(12):698713
2. Hunt R. Aliment Pharmacol Ther. 2005; 22(Suppl. 3): 10-19
 PUD Algorithm
Peptic Ulcer

No No
HP Stop NSAIDs
Response
Monotherapy PPI

Yes No
Response

Yes * Routine
HP Treatment Follow-up
Further
Evaluation * Consider maintenance
therapy in selected patients
Peptic Ulcer Disease
 PUD Demographics
• Higher prevalence in developing countries
– H. Pylori is sometimes associated with
socioeconomic status and poor hygiene
• In the US:
– Lifetime prevalence is ~10%.
– PUD affects ~4.5 million annually.
– Hospitalization rate is ~30 pts per 100,000
cases.
– Mortality rate has decreased dramatically in
the past 20 years
» approximately 1 death per 100,000 cases
Comparing Duodenal
and Gastric Ulcers
 Duodenal Ulcers

• duodenal sites are 4x as common as gastric sites

• most common in middle age
– peak 30-50 years
• Male to female ratio—4:1
• Genetic link: 3x more common in 1st degree
relatives
• more common in patients with blood group O
• associated with increased serum pepsinogen
• H. pylori infection common
– up to 95%
• smoking is twice as common
 Gastric Ulcers

• common in late middle age

– incidence increases with age
• Male to female ratio—2:1
• More common in patients with blood group A
• Use of NSAIDs - associated with a three- to four-
fold increase in risk of gastric ulcer
• Less related to H. pylori than duodenal ulcers –
about 80%
• 10 - 20% of patients with a gastric ulcer have a
concomitant duodenal ulcer
 Subjective Data

• Pain—”gnawing”, “aching”, or “burning”

– Duodenal ulcers: occurs 1-3 hours after a meal and
may awaken patient from sleep. Pain is relieved by
food, antacids, or vomiting.
– Gastric ulcers: food may exacerbate the pain while
vomiting relieves it.
• Nausea, vomiting, belching, dyspepsia, bloating,
chest discomfort, anorexia, hematemesis, &/or
melena may also occur.
– nausea, vomiting, & weight loss more common with
Gastric ulcers
 Objective Data

• Epigastric tenderness
• Guaic-positive stool resulting from occult blood
loss
• Succussion splash resulting from scaring or
edema due to partial or complete gastric outlet
obstruction
– A succussion splash describes the sound obtained by
shaking an individual who has free fluid and air or gas
in a hollow organ or body cavity.
– Usually elicited to confirm intestinal or pyloric
obstruction.
– Done by gently shaking the abdomen by holding either
side of the pelvis. A positive test occurs when a
 Differential Diagnosis

• Neoplasm of the stomach

• Pancreatitis
• Pancreatic cancer
• Diverticulitis
• Nonulcer dyspepsia (also called functional
dyspepsia)
• Cholecystitis
• Gastritis
• GERD
• MI—not to be missed if having chest pain
 Diagnostic Plan

• Stool for fecal occult blood

• Labs: CBC (R/O bleeding), liver function test,
amylase, and lipase.
• H. Pylori can be diagnosed by urea breath test, blood
test, stool antigen assays, & rapid urease test on a
biopsy sample.
• Upper GI Endoscopy: Any pt >50 yo with new onset of
symptoms or those with alarm markings including
anemia, weight loss, or GI bleeding.
– Preferred diagnostic test b/c its highly sensitive for dx of
ulcers and allows for biopsy to rule out malignancy and rapid
urease tests for testing for H. Pylori.
 Summary

• Defined peptic ulcer disease (PUD) and H. Pylori

(HP) infection
• List the major etiology and pathogenesis of PUD and
HP
• List the clinical symptoms of PUD
• Described the proposed mechanism by which H.
pylori causes ulcers
• Discussed the procedures used in the diagnosis of
PUD and H pylori infection
• Discuss medical management of PUD and H. pylori
infection
• List the complications of PUD
• Discussed controversial topics related to HP therapy
 H. pylori Infections
Marshall and Warren were awarded the
Nobel Peace Prize in 2005 for their pioneering
work with Helicobacter pylori.
 H. pylori (HP) Infection

• PUD is the most studied disease related

to HP infection
– HP may also be involved in GERD, certain
lymphomas, iron deficiency anemia, and
skin disorders
• Oral-oral and fecal-oral routes are
common methods of transmission
• More common in developing countries
Helicobacter pylori Gastritis

Images courtesy of
C. Mel Wilcox, MD.
 Risk Factors for Acquiring
H. pylori Infection

• Living in a developing country

• Poor socioeconomic status
• Asian ethnicity
• Family overcrowding
• Ethnic and genetic predisposition
– In the US- 60% of Hispanics have HP,
compared to 29% of Whites
– Is not a significant cause of mortality
 H. pylori Infection

• Testing
– Tests to identify active infection
» Fecal HP antigen test
» Carbon-13 Urea Breath Test
– Tests to detect antibodies (exposure)
» HP Serology
Diagnostic Testing for H. pylori

Invasive and Noninvasive Testing

 Invasive Test Sensitivity Specificity Usefulness
(%) (%)
Strategy of choice in
Endoscopy with children with
Biopsy persistent/severe
symptoms
Sensitivity reduced
Histology >95 100 by PPIs, bismuth,
antibiotics
Sensitivity reduced
by PPIs, bismuth,
Urease Activity 93 -97 >95 antibiotics, active
bleeding
Technically
Culture 70 – 80 100 demanding

Ables A et al. Amer Fam Physician 2007; 75(3):351-358

 Non-Invasive Sensitivity Specificity Usefulness
Test (%) (%)
Sensitivity and
Serology for specificity vary
85 79
IgG widely

Sensitivity reduced
Urea Breath by PPIs, bismuth,
95-100 91-98 antibiotics
Test

Test for cure 7 days

H pylori Stool after therapy is
91-98 94-99
Antigen accurate

Ables A et al. Amer Fam Physician 2007; 75(3):351-358

Managing H. pylori Infections
 H. pylori

NIH CONSENSUS STATEMENT (1994)

 “All patients with gastric or duodenal ulcers

who are infected..should be treated with
antimicrobials..”
 Therapy should not be initiated without
confirmation of the presence of H. Pylori
 Treatment recommendations should not be
influenced by NSAID use
 H. pylori
MIC90 FOR ACID SUPPRESSANT DRUGS

DRUG MIC90 (mcg/ml)

lansoprazole 6.25
ranitidine bismuth citrate 12.5
omeprazole 25.0
cimetidine 1,600.0
sucralfate 3,200.0
ranitidine 12,800.0
 H. pylori

ERADICATION RATES OF
H. PYLORI THERAPIES
100% 92%
84% 86%
82%
80% 77%
74% 73%
64%
60%

40%

20%
4
1 2 3

0%
Biaxin/Prilosec Biaxin/tritec Helidac Prevpac
 Eradication Rates of
FDA-Approved Therapies

100%
90% 92% Each pair of bars represents
84% 86% the two principal, pivotal U.S.
82%
77% 77% 77% studies cited in the prescribing
80% 74% 73% information* for each
66% combination, and thus, the
64%
range of eradication rates for
60% each therapy.
OC=Prilosec/Biaxin
LA=Prevacid/Amoxil
40%
RBC/C=Tritec/Biaxin
BMT/H2RA=Helidac
20% OAC=Prilosec/Amoxil/Biaxin
LAC=Prevacid/Amoxil/Biaxin
0% *evaluable analysis
OC LA RBC/C BMT/H2RA OAC LAC
 Treating Patients with HP

• Treat all H. pylori-infected ulcer patients

• Need to educate patients about adherence to
regimens
• No optimal single treatment regimen exists
• Use antibiotics and anti-ulcer drugs together
for treatment
• Maintenance therapy should only be used for
refractory or complicated ulcers
 Therapeutic Approaches
Drugs Dosage Duration
• Lansoprazole+ 30 mg BID
clarithromycin+ 500 mg BID
amoxicillin 1 g BID 14
• Omeprazole+ 40 mg QD
clarithromycin 500 mg TID 14
followed by omeprazole 20 mg QD 14
• Lansoprazole+ 30 mg TID
amoxicillin 1 g TID 14
• Ranitidine bismuth citrate+ 400 mg BID
clarithromycin 500 mg TID 14
followed by ranitidine bismuth 400 mg BID 14
• Bismuth subsalicylate+ 525 mg QID
metronidazole+ 250 mg QID
tetracycline+ 500 mg QID
H2 antagonist recommended dosage 14
 for patients with clarithromycin allergy or intolerance, or when H. pylori resistance is known or suspected.
 Antibiotics in H. pylori Regimens

• Antibiotics are effective in curing the infection

• Overuse can lead to resistance
• Treatment should be only for prescribed
period.
• Resistance problem has begun the use of
“rescue regimens” with antibiotics such as
levofloxacin and rifabutin
– Controversies exists concerning the use of rescue
regimens
 Emerging Problems with
HP Treatments

• Macrolide resistance a growing problem

– Mutations in HP may be the cause
– Of concern when seen in children
• High incidence of adverse effects
– Nausea, metallic taste
– D/C if skin rash, vomiting or diarrhea occur
• Should we treat patients without ulcers
but HP (+)? Current consensus says
YES.
 Adverse Effects with Antibiotics

• Clarithromycin
– diarrhea, nausea, abnormal taste, dyspepsia,
abdominal discomfort, headache
• Metronidazole
– Disulfiram-like reaction
– Metallic taste, nausea, headache, diarrhea,
peripheral neuropathy
• Amoxicillin- nausea, vomiting diarrhea
• Tetracycline- epigastric distress,
photosensitivity, hepatic, renal dysfunction
 Duration of Therapy

• Most recommended regimens have a

duration of therapy 10-14 days
• Recent studies have evaluated 1, 5, and
7-day therapies
– More evaluation needed
– Potential benefits of shorter regimens
include better adherence, reduced costs,
and fewer ADRs
Ables A et al. Amer Fam Physician 2007; 75(3):351-358
Short Course HP Therapy
 Short-course Therapies

1. Bismuth subsalicylate 524 mg QID +

amoxicillin 2 g QID + metronidazole
500 mg QID + lansoprazole 60 mg (one dose)
– 1 day duration
– 80 HP (+) patients with dyspepsia studied
– 95% eradication rate
2. Clarithromycin 500 mg BID – amoxicillin 1 g
BID + lansoprazole 30 mg BID
– 7 days duration
– 80 HP (+) patients with dyspepsia studied
– 90% eradication rate
 5-day HP Regimens
1. Amoxicillin 1 g BID + metronidazole 400 mg BID +
clarithromycin 250 mg BID + lansoprazole 30 mg BID
– 83 HP(+) pts with dyspepsia for at least 3 months of
endoscopically-confirmed ulcers
– 89% eradication rate
2. Same regimen as #1, with ranitidine 300 mg BID substituting for
lansoprazole
– 80 HP(+) pts with dyspepsia for at least 3 months of
endoscopically-confirmed ulcers
– 89% eradication rate
3. Same regimen as #1 with pre-treatment using
lansoprazole 30 mg BID x 2 day
– 80 HP(+) pts with dyspepsia for at least 3 months of
endoscopically-confirmed ulcers
– 81% eradication rate
 HP Treatment

• How do we treat the pregnant patient?

– Drugs to avoid include tetracycline,
bismuth subsalicylate (in third trimester)
• Follow-up with repeat UBT 4-12 weeks
after end of treatment.
• Good prognosis with adequate
treatment
• Reinfection rate is low with adequate
treatment
 Use of Probiotics

• Probiotics are live, nonpathogenic microbial food or

food supplements
• They can normalized GI flora
• The effects of various Pbs, in particular lactic acid-
producing bacteria such as Lactobacillus spp. and
Bifidobacterium spp., on H. pylori have been
investigated.
• Studies suggest that Lactobacillus and/or
Bifidobacterium supplementation may boost H. pylori
eradication rates, and with fewer side effects
• Combining these probiotics with standard HP therapy
may be beneficial; however it is unknown what is the
optimal probiotic dosage and duration of therapy
 Take Home Points
• Regimens must have at ● Eradication rates over
least 1 antibiotic 90%
• Regimens which contain ● Adherence issues
2 or more antibiotics
● H2RAs and PPIs can
may decr. resistance
be interchanged
• Don’t substitute
antibiotics in the same ● Select regimen based
class for those in FDA- on efficacy, safety,
approved regimens cost
• In general, no need for ● Watch for drug
H. Pylori by post- interactions, antibiotic
treatment testing (due to resistance
expense)
 Resistance

• Resistance to antibiotics, especially

macrolides and nitroimidazoles is
problematic
• Resistance is rare with amoxicillin and
tetracyline
• Quadruple drug therapy may be needed
 Recurrence

• Recurrence
– (+) UBT or fecal antigen test > 6 months
after treatment
– Risk factors include nonulcer dyspepsia,
persistence of chronic gastritis, female sex,
younger age, higher UBT test values,
higher rates of primary infection
– Retreat with another HP regimen
 Controversial Issues Involving
HP Treatment

• Dyspepsia
– Does HP cause dyspepsia in the absence of
ulcers?
– Does eradication of HP control dyspeptic
symptoms?
• GERD
– What is the relationship between HP and GERD?
– Should GERD patients be tested for HP?
• Confirmatory HP Testing
– If patient is asymptomatic, should a confirmatory
test after HP therapy be conducted?