Unit 3 Gastrointestinal Disorders P2 Peptic Ulcer

KPJ Healthcare University College
UNIT 3 GASTROINTESTINAL DISORDERS P2

PEPTIC ULCER
APPLIED THERAPEUTICS I
BPH 4384
1
By Shashidharan Menon
Definition
v A break in the mucosal lining of the stomach or duodenum more than 5 mm in diameter, with depth to
the submucosa. Ulcers smaller than this or without obvious depth are called erosions.
v Peptic ulcers result from an imbalance between factors promoting mucosal damage (gastric acid, pepsin,

Helicobacter pylori infection, non-steroidal anti-inflammatory drug use) and those mechanisms promoting
gastroduodenal defense (prostaglandins, mucus, bicarbonate, mucosal blood flow).
2
Epidemiology
v Accurate estimates require endoscopic studies because symptoms are insensitive and non-specific
indicators of peptic ulcers. A recent large endoscopic study of a population sample from Sweden reported
a prevalence of 4% (2% gastric, 2% duodenal ulcers).

v A much-cited but old study from the US quotes a lifetime prevalence of about 10% and an annual
incidence of around 0.3%, with similar results in a large survey published in 1996. Incidence of peptic ulcer
increases with age; gastric ulcers peak in the fifth to seventh decades and duodenal ulcers 10 to 20 years
earlier.
v Both sexes are similarly affected.
v The epidemiology of peptic ulcer disease largely reflects the epidemiology of the 2 major aetiologic
factors, Helicobacter pylori infection and use of non-steroidal anti-inflammatory drugs (NSAIDs).
v In the developed world, H pylori incidence has been slowly declining over the past 50 years and NSAID use
has increased. This has resulted in a decline in duodenal ulcers (almost always associated with H pylori
infection) and an increase in gastric ulcers (the main site of ulcers caused by NSAIDs). 3
Aetiology
v The 2 major aetiologic factors responsible for peptic ulceration are infection by the gram-negative gastric
pathogen Helicobacter pylori and the use of aspirin and other non-steroidal anti-inflammatory drugs
(NSAIDs).
v Duodenal ulcers are almost always associated with H pylori infection, and gastric ulcers with NSAID use.

v Rarer causes include gastric ischaemia (responsible for the 'stress ulcers' that occur commonly in patients
with multiple organ failure in intensive care units), Zollinger-Ellison syndrome (a syndrome of gastric acid
hypersecretion caused by a gastrin secreting neuro-endocrine tumour), certain medications (e.g.,
potassium chloride, bisphosphonates), infections (CMV in patients with HIV, and occasionally HSV), and
Crohn's disease. A small but increasing proportion of peptic ulcers seem truly idiopathic
4
Pathophysiology
v Peptic ulcers result from an imbalance between factors that can damage the gastroduodenal mucosal
lining and defense mechanisms that normally limit the injury. Aggressive factors include gastric juice
(including hydrochloric acid, pepsin, and bile salts refluxed from the duodenum), H pylori , and NSAIDs.

v Mucosal defenses comprise a mucus bicarbonate layer secreted by surface mucus cells forming a viscous
gel over the gastric mucosa; the integrity of tight junctions between adjacent epithelial cells; and the
process of restitution, whereby any break in the epithelial lining is rapidly filled by adjacent epithelial and
mucosal stromal cells migrating and flattening to fill the gap.
v Mucosal defenses depend on an adequate blood supply and on formation within the gastric mucosa.
v In general, duodenal ulcers are the result of hypersecretion of gastric acid related to H pylori infection
(the majority of cases), whereas secretion is normal or low in patients with gastric ulcers.In chronic H
pylori infection confined mainly to the gastric antrum leads to impaired secretion of somatostatin and
consequently increased gastrin release, resulting in gastric acid hypersecretion.
v In Zollinger-Ellison syndrome, a gastrin-secreting neuro-endocrine tumour is the stimulus for high rates of 5
gastric acid secretion.
Pathophysiology
v In gastric ulcers, longstanding H pylori infection throughout the stomach accompanied by severe
inflammation results in gastric mucin degradation, disruption of tight junctions between gastric epithelial
cells, and the induction of gastric epithelial cell death.

v NSAIDs cause injury directly (involving trapping hydrogen ions) and indirectly (a systemic effect involving
the inhibition of cyclo-oxygenases, especially COX-1) and increase bleeding risk through anti-platelet
actions. Chronic gastric ischaemia underlies the stress ulcers of patients in intensive care.
6
Classification
v Peptic ulcer is generally divided into gastric and duodenal ulcers.
Primary prevention

Ø Aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) should be used with caution, especially
in people older than 60 years of age and those who are also taking corticosteroids. Concurrent use of a
proton- pump inhibitor (PPI) may help for patients on long-term aspirin therapy for their coronary artery
disease, or if the NSAID cannot be discontinued.
Ø Recent guidelines also suggest considering testing for and treating Helicobacter pylori before starting
long-term NSAID therapy.
Ø Misoprostol, a prostaglandin E1 analog, is used for preventing NSAID-induced ulcers. Compliance with
misoprostol is a problem, particularly at high doses, because of its gastrointestinal side effects (abdominal
cramping and diarrhoea), and it is no more effective than PPIs.
Ø Prophylactic use of a PPI is also appropriate for patients in the ICU, especially those who require 7
mechanical ventilation or who have a coagulopathy
History
v NSAID use, H pylori infection, smoking, increasing age, history (or family history) of peptic ulcer disease,
and an intensive care stay are all key risk factors.
v A common clinical feature is dyspepsia, a chronic or recurrent abdominal pain or discomfort centred in
the upper abdomen. This symptom is commonly related to eating and is often nocturnal. However, the

absence of epigastric pain does not rule out the diagnosis. In patients with duodenal ulcers, the
abdominal pain may be severe and radiate through to the back as a result of penetration of the ulcer
posteriorly into the pancreas.
v Nausea and vomiting are uncommon, but if present, nausea may be relieved by eating. Vomiting generally
occurs after eating. Weight loss and anorexia may also be present.
v NSAID use and relief of the discomfort by use of antacids may support the diagnosis. However, these are
neither sensitive nor specific indicators. It should be noted that most people with dyspepsia do not have
peptic ulcer disease.
v If diarrhoea is also present, this may indicate Zollinger-Ellison syndrome. Rarely, nausea, vomiting, and 8
early satiety indicate pyloric stenosis (a complication of peptic ulcer disease).
v Importantly, peptic ulcers may cause no symptoms, especially in older people and those taking NSAIDs.
Physical Examination
v There may be some epigastric tenderness on palpation of the abdomen, but often there are no other
signs on examination. The patient can generally show the site of pain with one finger ('pointing sign’).
v Atypical presentations of peptic ulcer disease also occur. Gastric and duodenal ulcers may cause occult

blood loss and iron deficiency anaemia. Also, presentation may be sudden, with the signs of bleeding
(haematemesis and/or melaena and shock), or perforation with peritonitis.
v Rarely, a succussion splash may be heard in patients with pyloric stenosis (caused by gastric outlet
obstruction).
Endoscopy
v Clinical guidelines have been established to aid the evaluation of patients with dyspepsia, and these
should be applied to patients with suspected peptic ulcer disease.If there are any “alarm features” (i.e.,
red flags that suggest upper GI cancer, such as weight loss, bleeding, anaemia, vomiting, early satiety, or
dysphagia, or if the patient develops dyspeptic symptoms over the age of 55 years), endoscopy indicated.
9
v In the absence of alarm features, endoscopy is often unnecessary and is only indicated if symptoms
persist after treatment.
H pylori testing
v In the absence of alarm features or in patients 55 years of age or under, the patient should be tested for H
pylori using noninvasive methods (i.e., breath or stool antigen tests). Antibody testing gives less accurate

results.
v Histology and biopsy urease testing are more invasive laboratory tests that are performed on stomach
biopsies obtained during endoscopy. Both tests can detect H pylori ; however, the histology determines if
the ulcer is neoplastic (very rarely) and/or if there is evidence of an NSAID being the likely cause. These
tests are reserved for patients in whom endoscopy is indicated.
v Tests may give false-negative results in patients taking proton-pump inhibitors, bismuth, or other
medications that can interfere with the test.
v Switching to an H2 antagonist for 2 weeks prior to endoscopy may be an alternative, especially in patients
without alarm features. The clinical utility of the H pylori test is limited to populations with a prevalence
of H pylori infection of at least 10% to 15%, because of false-positive results at low prevalence. In practice, 10
this includes most urban areas and those with large immigrant, poor, and elderly populations
Other investigations
v Patients with suspected disease should have a stool haem test for occult blood, although a positive result
is uncommon, even in the presence of disease.

v A FBC should be ordered if the patient seems clinically anaemic or has evidence of GI bleeding.
v Zollinger-Ellison syndrome should be considered in patients with multiple or refractory ulcers, diarrhoea,
ulcers distal to the duodenum, or a family history of multiple endocrine neoplasia type 1. In these
patients, a fasting serum gastrin level should be ordered to look for evidence of gastrin hypersecretion.
11
Risk factors (Strong)
Helicobacter pylori infection
Ø H pylori is known to have a role in the aetiology. If those taking non-steroidal anti-inflammatory drugs
(NSAIDs) are excluded, about 90% of patients with duodenal ulcers and more than 70% with gastric ulcers
have H pylori infection compared with 30% to 50% in the general population. Infection increases the

lifetime risk of peptic ulcers.
Ø The likely mechanisms are through gastrin and acid hyper-secretion (duodenal ulcers) and local mucosal
damage (gastric ulcers).Eradication of infection prevents recurrence of both peptic ulcer disease and
bleeding.
Non-steroidal anti-inflammatory drug (NSAID)
Ø Risk of NSAID-induced ulcers increases with the presence of specific risk factors (particularly people over
60 years and those with a history of peptic ulcer), high doses of NSAIDs and duration of use, H pylori
infection, and concurrent use of corticosteroids.
12
Ø NSAIDs more commonly cause gastric ulcers than duodenal ulcers and do so by impairing mucosal
defenses, mainly mediated through cyclo-oxygenase (COX)-1. Selective COX-2 inhibitors are less likely to
cause peptic ulcers.
Risk factors (Strong)
Non-steroidal anti-inflammatory drug (NSAID)
Ø In patients using NSAIDs, peptic ulcer disease is more common in H pylori -positive than in H pylori -
negative patients. Stopping NSAID use (and treating H pylori , if present) reduces ulcer recurrence. If
NSAID use cannot be stopped, coprescription with a proton-pump inhibitor reduces recurrence.

Smoking
Ø Smoking is a risk factor for peptic ulcers. One meta-analysis found that smoking was responsible for 23%
of all peptic ulcers. The mechanisms are likely multi-factorial. While early studies reported that ulcers heal
faster after people stop smoking, the effect has not been seen when H pylori is treated.
Increasing age
Ø The incidence of peptic ulcers and their complications increases with age.
13
History & Examination Factors
Key diagnostic factors abdominal pain (common)
Ø Dyspepsia, a chronic or recurrent abdominal pain or discomfort centred in the upper abdomen, is a
common clinical feature.
Ø Commonly related to eating and is often nocturnal.

Ø In patients with duodenal ulcers, pain may be severe and radiate through to back as a result of
penetration of the ulcer posteriorly into the pancreas. 'pointing sign' (uncommon)
Ø Patient can show site of pain with one finger.
v Other diagnostic factors epigastric tenderness (common) :May occur on palpation of the abdomen.
v Nausea or vomiting (uncommon)

• Nausea is relieved by eating. • Vomiting occurs after eating. • May indicate pyloric stenosis.
v Weight loss or anorexia (uncommon): Patients may experience weight loss or anorexia. Diarrhoea
v Symptoms of anaemia (uncommon): Gastric and duodenal ulcers may cause iron deficiency anaemia.
Symptoms generally include fatigue, pica (abnormal craving or appetite for nonfood substances such as 14
dirt, ice, paint, or clay), and nail changes. Bleeding may be either occult (stool haem test positive) or overt
(haematemesis and/or melaena). This is a complication of peptic ulcer disease.
Diagnostic Tests

15
Diagnostic Tests

16
Differential Diagnosis

17
Differential Diagnosis

18
Step By Step Treatment Approach

19
Active Bleeding Ulcer
v Requires hospital admission. Most bleeding can be treated endoscopically. Concurrent use of an
intravenous infusion of a proton-pump inhibitor (PPI) reduces rebleeding and the need for surgery,
although it has no effect on all-cause mortality.

v Surgery is reserved for perforated ulcers and where endoscopic haemostasis of bleeding ulcers fails. Non-
steroidal anti-inflammatory drugs (NSAIDs), including aspirin, should be ceased before treatment.
v Blood transfusion can be considered to resuscitate acute volume loss, and a more restrictive transfusion
strategy (transfusion only for haemoglobin <70 g/L [7 g/dL]) has been shown to significantly improve
patient outcomes.
v After treatment, the presence of Helicobacter pylori should be assessed and the patient treated as for
patients with no active bleeding.
v In patients at increased risk of cardiovascular disease, restarting low-dose aspirin was associated with
increased recurrent bleeding but reduced overall mortality in a small controlled study.
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Active Bleeding Ulcer
Proton Pump Inhibitor
v Esomeprazole: 80 mg intravenous bolus given over 30 minutes initially, followed by an 8 mg/hour infusion
for 72 hours, then switch to oral dose and continue for 4-8 weeks after discharge

v Pantoprazole: 80 mg intravenous bolus given over 30 minutes initially, followed by an 8 mg/hour infusion
v Omeprazole: 80 mg intravenous bolus given over 30 minutes initially, followed by an 8 mg/hour infusion
v Concurrent use of an intravenous infusion of a PPI reduces rebleeding and the need forsurgery, although
it has no effect on all-cause mortality. After 72 hours, patient should be switched to oral dosing and
continue for 4 to 8 weeks after discharge.
2nd surgery
v Reserved for perforated ulcers and where endoscopic hemostasis of bleeding ulcers fails. 21
v After treatment, the presence of Helicobacter pylori should be assessed, and the patient treated
according to the guidelines for patients with no active bleeding.
No Active Bleeding: H Pylori Negative
v NSAIDs (including aspirin) should be discontinued, as this is the most likely cause in these patients. If this
is not possible, or if the patient takes low-dose aspirin for prophylaxis of cardiovascular disease,
prophylactic acid inhibitory therapy should be taken long term.

v To reduce the risk of gastroduodenal toxicity, including ulceration, a cyclo-oxygenase (COX-2) inhibitor
may be considered instead of the NSAID. However, due to the cardiovascular adverse effects associated
with COX-2 inhibitors, these drugs should be used only in patients who are at low risk for cardiovascular
disease.
v Ulcer healing therapy should then be instituted. If the patient has alarm features, endoscopy should be
performed before treatment is started. However, in the absence of alarm features, empirical treatment
with a PPI is appropriate.
v PPIs are the drug of choice for ulcer healing, given the simplicity of their dosing schedule and their
efficacy. Both PPIs and H2 antagonists inhibit acid secretion, but PPIs inhibit acid secretion to a greater
extent and heal peptic ulcers more rapidly.
22
v However, H2 antagonists may be used if the patient is unresponsive to PPIs.
v Sucralfate has similar ulcer healing rates to H2 antagonists. The mechanism of action is unknown; it
probably coats the ulcer base, thereby promoting ulcer healing. The frequent dosing schedule and large
tablet size is not conducive to good compliance and this drug is rarely recommended.

v Antacids are relatively ineffective and slow to produce healing, and are also not recommended.
v Acid suppressive therapy is generally continued for 4 weeks in patients with H pylori -negative duodenal
ulcers and for 8 weeks in patients with H pylori -negative gastric ulcers.
v Misoprostol is an option for the prevention of NSAID-induced gastric ulcers in patients who need to
continue NSAID therapy.
23
Proton Pump Inhibitor
Ø Omeprazole: 20-40 mg orally once daily OR

Ø Lansoprazole: 15-30 mg orally once daily OR

Ø Rabeprazole: 20 mg orally once daily OR
Ø Esomeprazole: 20-40 mg orally once daily
Ø Omeprazole/sodium bicarbonate: 20-40 mg orally once daily
Ø Dexlansoprazole: 30-60 mg orally once daily
H2 Antagonist
Ø Ranitidine: 150 mg orally twice daily

Ø Famotidine: 20 mg orally twice daily
Ø Nizatidine: 150 mg orally twice daily
v Sucralfate: 1 g orally four times daily

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v Misoprostol: 100-200 micrograms orally four times daily
No active bleeding: H pylori Positive
v If H pylori is present, eradication therapy should be started. If the patient has alarm features, endoscopy
should be performed before treatment is started. If patient is taking an NSAID (including aspirin), it should
be discontinued if possible.

v Triple therapy (a PPI plus 2 antibiotics) has historically been preferred over quadruple therapy (a PPI plus
bismuth plus 2 antibiotics) for initial treatment because of its relative simplicity; however, bismuth-based
regimens and sequential therapy (i.e., 5 days of a PPI plus amoxicillin, followed by 5 days of a PPI plus
clarithromycin and tinidazole) may provide improved eradication rates due to problems with increasing
antibiotic resistance with H pylori .
v All regimens contain antibiotics and therefore may cause diarrhoea, promote opportunistic infections,
and interfere with absorption of many other drugs, including oral contraceptives.
v Check for eradication of H pylori 1 month after the end of therapy. Continuation of acid suppressive
therapy after treatment of infection is not necessary in most cases.
v If the first treatment fails, at least 1 alternative regimen should be tried. If the organism cannot be 25
eradicated despite repeated attempts, long-term acid suppression therapy may be necessary to control
symptoms.
H pylori Positive
v If H pylori is present, eradication therapy should be started. If the patient has alarm features, endoscopy
should be performed before treatment is started. If patient is taking an NSAID (including aspirin), it should
be discontinued if possible.

v Eradication therapy leads to ulcer healing and a dramatic decrease in ulcer recurrence. Most regimens are
70% to 90% efficacious in practice, limited mainly by antibiotic resistance and patient adherence to the
regimen.
v Ideally, treatment with triple therapy is recommended for 14 days, as this duration has led to a
significantly increased H pylori eradication rate. Therapy should not be prescribed without documented
infection.
v Triple therapy (a PPI plus 2 antibiotics) has historically been preferred over quadruple therapy (a PPI plus
bismuth plus 2 antibiotics) for initial treatment because of its relative simplicity; however, bismuth-based
regimens and sequential therapy (i.e., 5 days of a PPI plus amoxicillin, followed by 5 days of a PPI plus
clarithromycin and tinidazole) may provide improved eradication rates due to problems with increasing
antibiotic resistance with H pylori . 26
Initial Antibiotic Therapy
v The choice of initial antibiotic regimen to treat H. pylori should
be guided by the presence of risk factors for macrolide
resistance and the presence of a penicillin allergy . In patients
with risk factors for macrolide resistance, clarithromycin-based

therapy should be avoided.
v Patients with risk factors for macrolide resistance — In patients

with risk factors for macrolide resistance, we use bismuth
quadruple therapy
v Patients without risk factors for macrolide resistance — In

patients without risk factors for macrolide resistance, we use
clarithromycin-based triple therapy with a proton pump
inhibitor (PPI), amoxicillin, and clarithromycin
v Other potential first-line treatment regimens include

clarithromycin-based hybrid or sequential therapy 27
Initial Antibiotic Therapy
Duration of therapy
v Recommend clarithromycin-based triple therapy and bismuth quadruple treatment regimens for H. pylori
be administered for 14 days. Our recommendations are largely consistent with current guidelines which
recommend extended (10 to 14 days) treatment with all antibiotic regimens for H. pylori.

Tolerability and compliance
v Side effects are reported in up to 50 percent of patients taking one of the triple therapy regimens. The
adverse effects are usually mild; fewer than 10 percent of patients stop treatment due to side effects .
Clarithromycin-based triple therapy and bismuth quadruple therapy appear to have similar efficacy,
compliance, and tolerability.
Bismuth quadruple therapy

v Bismuth quadruple therapy consists of bismuth subsalicylate, metronidazole, tetracycline, and a PPI given
for 14 days . A combination capsule containing bismuth subcitrate, metronidazole, and tetracycline
(Pylera) has been approved by the United States Food and Drug Administration. A regimen using the
combination capsule (three capsules four times daily plus PPI twice daily) is somewhat simpler than
standard quadruple therapy (four to eight pills four times daily and a PPI twice daily). 28
29
Clarithromycin-based therapy
Triple therapy
v Clarithromycin triple therapy consists of clarithromycin, amoxicillin, and a PPI, all given twice daily. We
suggest treatment for 14 days, as longer duration of treatment may be more effective in curing infection .
Metronidazole can be substituted for amoxicillin in penicillin-allergic individuals. PPI-clarithromycin-
metronidazole and PPI-clarithromycin-amoxicillin regimens are equivalent.

Concomitant therapy
v Concomitant therapy consists of a clarithromycin, amoxicillin, a nitroimidazole (tinidazole or
metronidazole), and a PPI administered together. If concomitant therapy is used to treat H. pylori, the
regimen should be continued for 10 to 14 days.
Hybrid therapy
v Hybrid therapy consists of amoxicillin and a PPI for seven days followed by amoxicillin, clarithromycin, a
nitroimidazole, and a PPI for seven days . Hybrid therapy has been suggested as an alternative to
clarithromycin triple therapy. However, the complexity of the treatment regimen has limited its use as a
first-line regimen in the treatment of H. pylori.
30
Sequential therapy
v The 10-day clarithromycin-containing sequential therapy regimen consists of amoxicillin and a PPI for five
days, followed by clarithromycin and tinidazole (eg, metronidazole) plus a PPI for five days .
Levofloxacin Based Therapy
Levofloxacin triple therapy
v Levofloxacin triple therapy consists of levofloxacin, amoxicillin, and a PPI for 10 to 14 days. In a network
meta-analysis eradication rates with levofloxacin triple therapy for 10 to 14 days were significantly higher
than clarithromycin triple therapy for seven days (90 versus 73 percent) . Metronidazole can be

substituted for amoxicillin in penicillin-allergic individuals.
Levofloxacin quadruple therapy

v Limited data support the use of quadruple therapy with levofloxacin, omeprazole, nitazoxanide, and
doxycycline (LOAD). In an open label prospective trial, H. pylori treatment-naïve patients randomized to
LOAD for 7 or 10 days had significantly higher eradication rates as compared with clarithromycin triple
therapy for 10 days (89, 90, and 73 percent, respectively) .
Levofloxacin sequential therapy

v Levofloxacin sequential therapy consists of amoxicillin and a PPI for five to seven days followed by
levofloxacin, amoxicillin, a nitroimidazole and a PPI for five to seven days. A meta-analysis of six
international trials compared the efficacy of fluoroquinolone sequential therapy for 10 to 14 days and
either clarithromycin triple therapy for 7 to 14 days or standard sequential therapy for 10 days [39]. The 31
pooled eradication rate with fluoroquinolone sequential therapy was significantly higher as compared
with clarithromycin triple or standard sequential therapies combined (88 versus 71 percent).
Confirmation of Eradication
v Tests to confirm eradication should be performed in all patients treated for H. pylori. Eradication may be
confirmed by a urea breath test, fecal antigen test, or upper endoscopy performed four weeks or more
after completion of antibiotic therapy.

v PPI therapy should be withheld for one to two weeks prior to testing . Endoscopy with biopsy for culture
and sensitivity should be performed in patients with persistent H. pylori infection after two courses of
antibiotic treatment.
32
Treatment Failure
Factors associated with antibiotic treatment failure —
v Factors associated with treatment failure include poor patient compliance and resistance of the patient’s
H. pylori strain to prescribed antibiotics. H. pylori is naturally resistant to several commonly used

antibiotics, including vancomycin, trimethoprim, and sulfonamides.
v A specific mutation leading to clarithromycin resistance appears to be associated with a reduced

likelihood of eradication.
v Prior use of macrolide antibiotics, metronidazole, and levofloxacin increases the risk of H. pylori resistance
to these antibiotics. Clarithromycin resistance has a greater effect on treatment efficacy as compared
with metronidazole resistance .
v The impact of metronidazole resistance can be overcome by increasing the dose, duration, or frequency
of administration of metronidazole. Resistance rates to amoxicillin, tetracycline, and rifabutin are low (<5
percent).
33
Salvage therapy for persistent H. pylori infection
v In patients with persistent H. pylori infection, the choice of antibiotic therapy should be guided by the
patient’s initial treatment regimen, the use of other antibiotics, and the presence of relevant antibiotic
allergies. Antibiotics included in the initial regimen should generally be avoided .

v However, amoxicillin can be reused as resistance rarely develops. Patients with a reported history of
penicillin allergy should be referred to an allergist to determine if they have a true penicillin allergy.
v Culture with antibiotic sensitivity testing should be performed to guide antibiotic treatment in patients
who have failed two prior treatment regimens. Compliance with medications should also be reinforced.
We reserve the use of rifabutin-containing regimens for patients with ≥3 previous antibiotic failures.
34
Salvage therapy for persistent H. pylori infection

35
36
Salvage Regimens
Bismuth quadruple therapy
v Bismuth quadruple therapy should be used for 14 days when used as salvage regimen. In randomized
trials performed in Europe, United States, and Asia eradication rates with 14-day salvage bismuth
quadruple therapy were approximately 80 percent .

v Eradication rates were significantly higher in studies performed in Asia as compared with Europe and the
United States (82 versus 74 percent) . The overall eradication rate for 14-day bismuth quadruple therapy
in these trials was higher in patients who had previously failed clarithromycin-based regimens without
bismuth as compared with bismuth quadruple treatment (100 versus 53 percent).
Levofloxacin triple therapy
v Levofloxacin-based triple therapy has demonstrated efficacy as a salvage regimen in patients who have
failed initial clarithromycin triple therapy or bismuth quadruple therapy. Levofloxacin triple therapy has
also demonstrated efficacy in patients who have failed two prior attempts at treatment.
37
v In a pooled analysis from six European cohort studies, when used as a salvage regimen in patients who
had failed two previous eradication attempts, levofloxacin triple therapy administered for 10 days has a
pooled eradication rate of 73 percent.
Salvage Regimens
High-dose dual therapy
v High dose dual therapy with amoxicillin and proton pump inhibitor (PPI) for 14 days is a salvage treatment
option, particularly in patients in whom dual metronidazole/clarithromycin resistance or levofloxacin
resistance is suspected. The pooled eradication rate of high-dose dual therapy with amoxicillin and PPI as

a salvage regimen in three randomized trials performed in Europe and Asia was 78 percent.
Clarithromycin based concomitant therapy
v Of the clarithromycin-based regimens, only concomitant therapy (clarithromycin, amoxicillin, a

nitroimidazole, and a PPI) should be used as a salvage regimen. Clarithromycin-based therapy should be
used only in patients with no risk factors for macrolide resistance (no prior macrolide exposure and local
clarithromycin resistance known to be <15 percent).
Rifabutin triple therapy
v The rifabutin-based triple regimen consists of rifabutin, amoxicillin, and a PPI twice daily for 10 days. In a 38
meta-analysis of cohort studies that evaluated the efficacy of rifabutin triple therapy as salvage
treatment, pooled eradication rates as a second, third, or fourth/fifth line agent were 79, 66, and 70
percent respectively.
Adjuvant Therapies
Statins
v Addition of statin therapy as an adjuvant to triple therapy has been associated with a reduction in H.
pylori mediated inflammation and an increase in H. pylori eradication rates . However, large trials are

needed to confirm these findings.
Probiotics
v Probiotics may have an inhibitory effect on H. pylori. In addition, they may improve compliance with
treatment by reducing antibiotic side effects. A meta-analysis that included 10 clinical trials of adjuvant
probiotics in patients with H. pylori infection demonstrated higher cure rates and a reduction in the
incidence of side effects in patients who received probiotic supplementation (pooled OR 2.1 and 0.3,
respectively).
Vonoprazan
v Limited data from retrospective studies suggest that the use of vonoprazan, an oral potassium- 39
competitive acid blocker (PCAB), rather than a proton pump inhibitor, with amoxicillin and clarithromycin
may increase H. pylori eradication rates
Treatment During Pregnancy and Lactation
v When peptic ulcer disease is diagnosed in a woman who is pregnant, the mainstay of treatment is
typically acid suppression .
v If H. pylori is present, treatment is typically deferred until after delivery. However, with the exception of

bismuth, fluoroquinolones, and tetracycline, the other medications used for H. pylori eradication are low
risk in pregnancy, especially after 14 weeks.
v This includes clarithromycin, amoxicillin, and probably metronidazole. Moreover, there is some evidence
that H. pylori can cause severe nausea and vomiting in pregnancy, including hyperemesis gravidarum.
Thus, if indicated, H. pylori treatment should be considered in pregnancy.
v Some of the medications typically used for the treatment of H. pylori are possibly unsafe for nursing
infants (eg, bismuth, metronidazole, levofloxacin).
40
Monitoring
v Patients with a gastric ulcer may have an endoscopy 6 to 8 weeks after treatment is started to check ulcer
healing and to rule out gastric cancer as a small number of gastric cancers may present as gastric ulcers.
v However, recent guidelines are less strict about this. Patients with uncomplicated duodenal ulcers do not

need follow-up endoscopy.
v Patients with documented Helicobacter pylori infection should be evaluated for eradication 1 month after
the end of antimicrobial therapy.
41
42
Case & Answer
v A 62-year-old man presents with abdominal pain and heartburn that occur two to three times per week.
He also reports a 10-pound (4.5-kg) weight loss in the last 6 weeks, despite not dieting or increasing
physical activity. He does not report any recent antibiotic use.

v PMH: Hypertension × 5 years
v FH: Mother alive at 84 with hypertension, type 2 diabetes;
v father deceased at 68 following MI
v SH: Smokes half pack per day; no alcohol or illicit drug use
v Allergies: Penicillin
v Meds: Lisinopril/hydrochlorothiazide 20/25 mg daily, acetaminophen 500 mg as needed for headache
1. Based on this patient’s clinical presentation, what is the most appropriate course of action to establish a
diagnosis?
2. The patient receives a diagnosis of H. pylori infection based on the diagnostic method recommended.
What eradication therapy would you recommend?
43
3. The patient completed the course of eradication therapy recommended; however, he returns with
similar symptoms 3 months later. What regimen would you recommend for eradication therapy?

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