Sequential therapy using high-dose esomeprazole-amoxicillin followed by gatifloxacin for Helicobacter pylori infection.

BACKGROUND: The success rate of current anti-Helicobacter pylori triple therapies in now generally 80% or less. Sequential therapy has proved superior. AIM: To test a new sequential therapy for H. pylori eradication. METHODS: This was a pilot study of a sequential therapy consisting of 40 mg of esomeprazole and 1 g amoxicillin t.d.s., for 12 days. On days 6 through 12 gatifloxacin (400 mg in the morning) was added. Outcome was accessed 4 or more weeks after ending antibiotic therapy. Both naive and treatment failures were eligible. RESULTS: Thirty patients were entered in the study. One was lost to follow-up and one stopped early because of side effects. The success rate intention-to-treat was 80% (95% CI: 61-92%). The per-protocol eradication rate was 85.7% (95% CI: 67-95%); two of the four failures had pre-treatment gatifloxacin-resistant H. pylori. Side effects were reported by 13 patients (46%) and were generally mild with diarrhoea being most common (n = 6). Only one patient stopped medicine because of side effects of dizziness (severe) and diarrhoea (mild). CONCLUSIONS: Sequential therapy using the combination of a high dose of proton-pump inhibitor and amoxicillin followed gatifloxacin was effective, but pre-treatment susceptibility testing may become necessary as fluoroquinolone resistance increases.

Rabeprazole containing triple therapy to eradicate Helicobacter pylori infection on the Texas-Mexican border.

BACKGROUND: Antibiotic resistance and duration of therapy influence the success of proton-pump inhibitor-containing Helicobacter pylori eradication therapy. Clarithromycin resistance is associated with treatment failure. AIM: To examine the success of a 7-day rabeprazole-clarithromycin-amoxicillin therapy in the study population. METHODS: Adults from Ciudad Juarez with H. pylori infections identified by culture or histology received rabeprazole 20 mg, clarithromycin 0.5 g and amoxicillin 1 g, each b.d. for 7 days. Outcome was assessed by 13C-urea breath test carried out 4+ weeks after treatment. RESULTS: A total of 111 patients were enrolled and evaluated by urea breath test; 102 completed the full 7 days therapy. Two deviated from protocol, and five stopped because of adverse events. The cure rate (intention-to-treat) was 85% (95% CI: 78-91%); the per-protocol cure rate was 85% (95% CI: 78-91%). Side-effects were not serious and only 6.6% of those with adverse events stopped medication. Only three isolates were clarithromycin-resistant and none was cured. Compliance explained most of the successes. CONCLUSIONS: In the study population a 7-day rabeprazole triple eradication therapy was both effective and well-tolerated. Clarithromycin resistance was uncommon. We observed a slightly better outcome but consistent with results from recent large studies in US populations.

Novel bismuth-metronidazole-tetracycline triple-layer tablet for treatment of Helicobacter pylori.

BACKGROUND: Current anti-Helicobacter pylori treatment regimens are costly and because of the increasing antibiotic resistance, are becoming ineffective. AIM: To evaluate a triple-layer tablet containing 100 mg bismuth subcitrate, 250 mg metronidazole, and 250 mg tetracycline in a single triple-layer tablet. METHODS: H. pylori-infected adult patients received bismuth-metronidazole-tetracycline (two tablets, t.d.s.) and ranitidine (300 mg) once daily for 14 days. Efficacy was determined using 13C-urea breath testing. RESULTS: Thirty-three of 35 enrolled patients were available for evaluation; using the protocol-specified modified intention-to-treat analysis, five failed treatment, two were lost to follow-up (cure rate per-protocol = 85.7%, intention-to-treat = 78.7%). The cure rate among metronidazole-susceptible strains was 100% (22 of 22) (95% confidence interval 84-100%) compared with 55% (five of nine intention-to-treat) (95% confidence interval 21-86%) among metronidazole-resistant strains. In four cases, therapy was truncated at 4-7 days because of side-effects; yet the treatment was effective in three. The three metronidazole-susceptible but clarithromycin-resistant infections were cured. CONCLUSION: This novel triple-layer tablet combination therapy was effective in all patients with metronidazole-susceptible H. pylori and many of those with resistant organisms. A greater degree of acid suppression may further improve effectiveness.

Atrophic gastritis in young children and adolescents.

BACKGROUND: Helicobacter pylori associated gastric cancer arises via a multistage process, with atrophic gastritis being the precursor lesion. Helicobacter pylori is typically acquired in childhood, yet little is known of the prevalence of atrophic gastritis in childhood. AIM: To study atrophic gastritis among children from countries with high gastric cancer incidence. METHODS: Sections from topographically mapped gastric biopsy specimens from children undergoing clinically indicated endoscopy in Korea and Colombia were evaluated using visual analogue scales. Atrophy was defined as loss of normal glandular components, including replacement with fibrosis, intestinal metaplasia (IM), and/or pseudopyloric metaplasia of the corpus (identified by the presence of pepsinogen I in mucosa that was topographically corpus but phenotypically antrum). RESULTS: One hundred and seventy three children, 58 from Korea (median age, 14 years) and 115 from Colombia (median age, 13 years), were studied. Helicobacter pylori was present in 85% of Colombian children versus 17% of Korean children (p<0.01). Atrophic mucosa near the antrum-corpus border was present in 16% of children, primarily as pseudopyloric metaplasia (31%, IM; 63%, pseudopyloric metaplasia; 6%, both). The median age of children with corpus atrophy was 15 (range, 7-17) years. CONCLUSION: Gastric atrophy occurs in H pylori infected children living in countries with high gastric cancer incidence. Identification and characterisation of the natural history of H pylori gastritis requires targeted biopsies to include the lesser and greater curve of the corpus, starting just proximal to the anatomical antrum-corpus junction, in addition to biopsies targeting the antrum and cardia.

CagA in Barrett's oesophagus in Colombia, a country with a high prevalence of gastric cancer.

BACKGROUND: In the USA, atrophic gastritis and gastric cancer are rare, whereas gastro-oesophageal reflux disease (GERD) is common. Infection with Helicobacter pylori, especially a CagA positive strain, is unusual in patients with GERD/Barrett's oesophagus in the USA. AIM: To examine the relation between Barrett's oesophagus and CagA positive H pylori in Colombia, a country with a high prevalence of CagA positive H pylori associated atrophic gastritis and gastric cancer. METHODS: Helicobacter pylori and CagA status was determined among Colombian patients with long segment Barrett's oesophagus and a control group with simple H pylori gastritis. Helicobacter pylori status was determined using a triple stain and CagA status was determined by immunohistochemistry using a specific rabbit anti-CagA serum. RESULTS: Gastric and oesophageal mucosal biopsies were obtained from 51 patients--39 men (mean age, 57.8 years; SD, 13.1) and 12 women (mean age, 51.8 years; SD, 14.4)--with documented long segment Barrett's oesophagus. The results were compared with 24 Colombian patients with H pylori gastritis without oesophageal disease. Thirty two patients with Barrett's oesophagus had active H pylori infection. CagA status was evaluated in a subset of 23 H pylori infected patients with Barrett's oesophagus, and was positive in eight of these patients compared with 19 of 24 controls (p = 0.01). CONCLUSIONS: Although most Colombian patients with Barrett's oesophagus had H pylori infection, CagA positive infections were unusual. These data illustrate how consistent corpus inflammation reduces acid secretion, which prevents Barrett's oesophagus among those with abnormal gastro-oesophageal reflux barriers.

Early events in proton pump inhibitor-associated exacerbation of corpus gastritis.

BACKGROUND: Antisecretory therapy may exacerbate Helicobacter pylori corpus gastritis. The rate and mechanism(s) remain unknown. AIM: To investigate the early events in proton pump inhibitor therapy on antral and corpus H. pylori gastritis. METHODS: Nine H. pylori-infected volunteers underwent gastric biopsy with jumbo forceps for culture and histology. Histology was scored in the range 0-5 using a visual analogue scale. The depth of inflammation in gastric pits was scored in the range 1-3 (superficial or less than one-third, one-third to two-thirds and greater than two-thirds of the gastric pit, respectively). Tissue interleukin-1 beta and interleukin-8 levels were measured by enzyme-linked immunoabsorbent assay. Omeprazole, 20 mg b.d., was given for 6.5 days and biopsies were repeated on day 7. RESULTS: Proton pump inhibitor therapy resulted in a fall in H. pylori density in the antrum and corpus. Inflammation and tissue levels of interleukin-8 and interleukin-1 beta decreased in the antrum and increased in the corpus mucosa. There was a significant increase in the depth of inflammation to include the proliferative zone in the corpus. CONCLUSIONS: Within 1 week of starting proton pump inhibitor therapy, there was a marked extension of corpus inflammation into the gastric pit and an increase in corpus mucosal interleukin-1 beta and interleukin-8 levels. H. pylori eradication should be considered for all patients receiving long-term antisecretory therapy.

One-week triple therapy with omeprazole, amoxycillin and clarithromycin for treatment of Helicobacter pylori infection.

BACKGROUND: Multi-drug regimens are generally required to reliably cure H. pylori infection. We previously demonstrated that a 2-week three-times-a-day regimen of amoxycillin and clarithromycin was effective against H. pylori infection. OBJECTIVES: To evaluate the efficacy and side-effects of a 1-week twice-daily dosing schedule for the treatment of H. pylori infection. METHODS: We studied the efficacy of 1-week of therapy with 20 mg of omeprazole, 1 g of amoxycillin and 250 mg of clarithromycin, all twice daily H. pylori status was determined at entry and 4 or more weeks after completing antimicrobial therapy using histology (Genta stain) and culture. RESULTS: Thirty-one patients with documented peptic ulcer disease and H. pylori infection were treated. The H. pylori infection was cured in 24 (77%, 95% CI = 58-90%) (intention-to-treat). In a per protocol analysis the cure rate was 23 of 29 patients (79%, 95% CI = 60-92%). One patient took only 43% of the study drugs and another withdrew following development of an anaphylactic reaction to study medication. Mild side-effects were reported by 16% including diarrhoea, headache and altered taste. Compliance averaged 95%. Pretreatment clarithromycin resistance averaged 5% and had not been acquired by any strains post-therapy. CONCLUSION: This combination of omeprazole, amoxycillin and low-dose clarithromycin resulted in a relatively low cure rate even in patients with clarithromycin-sensitive isolates. Large comparative studies will be needed to define the optimal duration, dose and dosing interval if this combination of drugs is to become competitive.

High-dose proton pump inhibitor plus amoxycillin for the treatment or retreatment of Helicobacter pylori infection.

BACKGROUND: The combination of 120 mg of omeprazole (40 mg t.d.s.) and amoxycillin has been reported to be effective for treating H. pylori infections. METHODS: Normal volunteers with H. pylori infection received high-dose omeprazole (40 mg t.d.s.) or lansoprazole (60 mg t.d.s.) plus amoxycillin 750 mg t.d.s. for 14 days. The studies were open label and not randomized as those receiving omeprazole plus amoxycillin had previously failed lower dose omeprazole (20 mg b.d.) plus amoxycillin therapy more than 6 months previously. Those receiving lansoprazole plus amoxycillin had not been previously treated. Four to 6 weeks after ending antimicrobial therapy, H. pylori status was determined by Genta stain of gastric mucosal biopsies. RESULTS: Forty-three volunteers entered the study and 41 completed it. The overall success with high-dose proton pump inhibitor plus amoxycillin was 34.9%. For the individual regimens the per-protocol results were 48% (95% CI = 28-69%) with lansoprazole and 12.5% (95% CI = 2-38%) with omeprazole. Compliance was > 95% for both regimens. Side-effects were experienced by four lansoprazole and three omeprazole subjects, and caused two omeprazole subjects to withdraw. Cure rates were similar among different races and ethnic groups, between men and women, and between smokers and non-smokers. The level of the pre-treatment urea breath test also did not predict outcome. CONCLUSION: High-dose proton pump inhibitor plus amoxycillin combinations for treatment of H. pylori infection yielded unacceptable results, as the 95% confidence intervals did not include an 80% cure rate. These combinations do not yield consistent results worldwide and cannot be recommended as primary therapy.

Metronidazole, ranitidine and clarithromycin combination for treatment of Helicobacter pylori infection (modified Bazzoli's triple therapy).

BACKGROUND: Multi-drug regimens are generally required to reliably cure Helicobacter pylori infection. Metronidazole, clarithromycin and omeprazole has proven to be an effective combination therapy with a cure rate of 90% or greater. METHODS: We evaluated a 14-day combination regimen for H.pylori infection consisting of metronidazole 500 mg b.d., clarithromycin 250 mg b.d. and ranitidine 300 mg b.d. (MRC) instead of omeprazole. Ranitidine alone was continued for an additional 4 weeks. H. pylori status was determined by rapid urease testing, histopathology using the Genta stain, and by culture at entry and 4 weeks after completing antimicrobial therapy. RESULTS: Twenty-seven patients with documented peptic ulcer disease and H. pylori infection were treated. Five had previously failed macrolide-based antimicrobial therapy; none had received metronidazole. All ulcers were healed at week 6 except one patient taking naproxen; his H. pylori infection was cured. Overall, H. pylori infection was cured in 78% (95% CI = 58-91%). In patients with clarithromycin-sensitive isolates, the cure rate was 20 of 23 (87%, 95% C.I. = 66-97%); only one of four patients (25%) with clarithromycin-resistant isolates was cured. In contrast, four of five patients with metronidazole-resistant isolates were cured (80%). In patients with isolates sensitive to both antibiotics, the cure rate was 16 of 18 (89%, 95% C.I. = 65-99%). Mild side effects were reported by 27%, including diarrhoea and altered taste. Compliance averaged 98%. CONCLUSION: These results suggest that the combination of metronidazole, ranitidine and clarithromycin results in high cure rates in patients with clarithromycin-sensitive isolates. Omeprazole may not be required for Bazzoli's triple therapy; and large multicentre comparative trials are indicated.

Twice a day quadruple therapy (bismuth subsalicylate, tetracycline, metronidazole plus lansoprazole) for treatment of Helicobacter pylori infection.

BACKGROUND: Quadruple therapy (bismuth, metronidazole and tetracycline (BMT) + proton pump inhibitor) is touted as being > 95% effective, regardless of metronidazole resistance. We tested a 10-day b.d. quadruple therapy for treatment of H. pylori infection. METHODS: Anti-H. pylori therapy consisted of lansoprazole 15 mg b.d. plus tetracycline 500 mg b.d., metronidazole 500 mg b.d., and swallowable Pepto-Bismol caplets (2 b.d.) for 10 days. H. pylori status was evaluated by culture and histology before and 4 or more weeks after therapy. RESULTS: The cure rate for intention-to-treat was 70%. Treatment success was calculated overall and separately in relation to antimicrobial resistance patterns. The cure rate among the metronidazole-sensitive isolates was 89.7% (26 of 29) vs. 41.2% (7 of 17) of the metronidazole-resistant isolates (P < 0.005). Moderate (n = 1) or severe (n = 3) side-effects were experienced in four patients with only one withdrawing because of side-effects. CONCLUSION: Twice a day quadruple therapy is effective for metronidazole-sensitive strains but its usefulness is markedly reduced by the presence of pre-treatment metronidazole resistance. Twice a day quadruple therapy can be recommended in locations where background metronidazole resistance is uncommon. Possibly, 14-day therapy or a higher dosage of metronidazole provide better results with metronidazole-resistant H. pylori.

Metronidazole, omeprazole and clarithromycin: an effective combination therapy for Helicobacter pylori infection.

BACKGROUND: Successful treatment of Helicobacter pylori infection results in cure of peptic ulcer disease. Multi-drug regimens are needed to cure this infection. We studied the effectiveness and side effect profile of two antibiotics active against Helicobacter pylori, metronidazole and clarithromycin, combined with omeprazole. METHODS: We evaluated a combination therapy for H. pylori infection consisting of metronidazole (500 mg b.d.), omeprazole (20 mg b.d.), and clarithromycin (250 mg b.d.) for 2 weeks, followed by ranitidine 300 mg daily for 4 weeks. RESULTS: Thirty-three patients with documented H. pylori infection were studied. Twenty had previously failed antimicrobial therapy, including one with metronidazole-based triple therapy and eight with macrolide-based therapy (five with clarithromycin-based therapy), and 11 with amoxycillin, tetracycline, and bismuth. H. pylori status was determined by histopathology using the Genta stain and by culture. H. pylori status was determined at entry and 4 weeks after completing antimicrobial therapy. The H. pylori infection was cured in 88% (95% CI = 72%-96%) including 90% of those who had failed previous anti-H. pylori therapies. Mild side effects were reported by 18%. CONCLUSION: We conclude that the combination of metronidazole, omeprazole and clarithromycin is an effective treatment for H. pylori infection.

Ranitidine bismuth citrate, tetracycline, clarithromycin twice-a-day triple therapy for clarithromycin susceptible Helicobacter pylori infection.

BACKGROUND: Although many combination therapies have been proposed, there is still interest in identifying simple, inexpensive, effective protocols that have high rates of success. AIM: To investigate the role of the new soluble form of bismuth, ranitidine bismuth citrate, in twice-a-day therapy for Helicobacter pylori infection. METHODS: Patients with histologically and culture proven H. pylori infection received ranitidine bismuth citrate 400 mg, tetracycline HCl 500 mg, and clarithromycin 500 mg, each b.d. for 14 days, followed by 300 mg ranitidine once a day for 4 additional weeks. Outcome was assessed 4 or more weeks after the end of antimicrobial therapy by repeat endoscopy with histology and culture (49 patients) or urea breath testing (14 patients). RESULTS: Sixty-three patients completed the therapy, 59 men and four women (average age 56.7 years; range 31-75 years). All patients had clarithromycin-susceptible strains prior to therapy. H. pylori infection was cured in 94% (95% CI: 85-98%). There was a therapy failure in one patient who took the medicine for only 1 day and stopped because of side-effects. Three of the isolates from treatment failures were available post-failure; two were clarithromycin-resistant and one was susceptible. Side-effects were severe in two patients (3%) and moderate in three (primarily diarrhoea). CONCLUSIONS: Twice-a-day ranitidine bismuth citrate, tetracycline, clarithromycin triple therapy was well tolerated and effective for the treatment of H. pylori infection in patients with clarithromycin-susceptible H. pylori.

Nitrofurantoin quadruple therapy for Helicobacter pylori infection: effect of metronidazole resistance.

BACKGROUND: Antibiotic resistance has increasingly been recognized as the major cause of treatment failure for Helicobacter pylori infection. New therapies for patients with metronidazole- or clarithromycin-resistant H. pylori are needed. AIM: To investigate the role of nitrofurantoin quadruple therapy for the treatment of H. pylori. METHODS: Patients with confirmed H. pylori infection received nitrofurantoin (100 mg t.d.s.), omeprazole (20 mg b.d.), Pepto-Bismol (two tablets t.d.s.), and tetracycline (500 mg t.d.s.) for 14 days. Four or more weeks after the end of therapy, outcome was assessed by repeat endoscopy with histology and culture or urea breath testing. RESULTS: Thirty patients were entered, including 25 men and five women; the mean age was 54.9 years. The most common diagnoses were duodenal ulcer (23%) and GERD (18%). The intention-to-treat cure rate was 70% (95% CI: 50.6-85%). Nitrofurantoin quadruple therapy was more effective with metronidazole-sensitive strains (88%; 15 out of 17) than with metronidazole-resistant strains (33%; three out of nine; P=0.008). Two of the treatment failures had pre-treatment isolates susceptible to metronidazole, which were resistant after therapy. CONCLUSIONS: Because nitrofurantoin quadruple therapy performed inadequately in the presence of metronidazole resistance, we conclude that nitrofurantoin is unlikely to find clinical utility for the eradication of H. pylori.

Meta-analysis: proton pump inhibitor or H2-receptor antagonist for Helicobacter pylori eradication.

AIM: To compare H2-receptor antagonists and proton pump inhibitors as adjuvants to triple therapy for Helicobacter pylori eradication. METHODS: H. pylori-infected patients with peptic ulcer were randomized to receive either 300 mg nizatidine or 30 mg lansoprazole plus 1 g amoxicillin and 500 mg clarithromycin taken b.d. for 7 days. H. pylori eradication was assessed 4 weeks after therapy. Using meta-analytical techniques, we combined the results of this study with other randomized controlled comparisons of H2-receptor antagonists and proton pump inhibitors as adjuvants to triple therapy. RESULTS: One hundred and one patients were randomized. H. pylori eradication was 94% (47/50) [95% confidence interval (CI), 83-99%] (intention-to-treat) in the H2-receptor antagonist group vs. 86% (44/51) (95% CI, 74-94%) in the proton pump inhibitor group (P = 0.3). There has been a total of 12 similar studies (1415 patients). The overall efficacy was similar in intention-to-treat analysis: 78% (549/701) with H2-receptor antagonists vs. 81% (575/714) with proton pump inhibitors (odds ratio, 0.86; 95% CI, 0.66-1.12). A non-significant trend favouring H2-receptor antagonist (79% vs. 69%; odds ratio, 1.14; 95% CI, 0.76-1.71; P = 0.5) was seen in the comparison of clarithromycin-containing regimens. In contrast, in non-clarithromycin-containing trials, there was a slight, but significant, advantage with proton pump inhibitors (85% vs. 78%; odds ratio, 0.64; 95% CI, 0.45-0.92; P = 0.02). CONCLUSION: Overall, proton pump inhibitor and H2-receptor antagonist antisecretory agents appear to be similarly effective as adjuvants for H. pylori triple therapy. It is unlikely that the direct anti-H. pylori effect of proton pump inhibitors is responsible for their ability to enhance anti-H. pylori therapy.

Review article: Mycobacterium avium subsp. paratuberculosis as one cause of Crohn's disease.

A number of theories regarding the aetiology of Crohn's disease have been proposed. Diet, infections, other unidentified environmental factors and immune disregulation, all working under the influence of a genetic predisposition, have been viewed with suspicion. Many now believe that Crohn's disease is a syndrome caused by several aetiologies. The two leading theories are the infectious and autoimmune theories. The leading infectious candidate is Mycobacterium avium subspecies paratuberculosis (Mycobacterium paratuberculosis), the causative agent of Johne's disease, an inflammatory bowel disease in a variety of mammals including cattle, sheep, deer, bison, monkeys and chimpanzees. The evidence to support M. paratuberculosis infection as a cause of Crohn's disease is mounting rapidly. Technical advances have allowed the identification and/or isolation of M. paratuberculosis from a significantly higher proportion of Crohn's disease tissues than from controls. These methodologies include: (i) improved culture techniques; (ii) development of M. paratuberculosis-specific polymerase chain reaction assays; (iii) development of a novel in situ hybridization method; (iv) efficacy of macrolide and anti-mycobacterial drug therapies; and (v) discovery of Crohn's disease-specific seroreactivity against two specific M. paratuberculosis recombinant antigens. The causal role for M. paratuberculosis in Crohn's disease and correlation of infection with specific stratification(s) of the disorder need to be investigated. The data implicating Crohn's as an autoimmune disorder may be viewed in a manner that supports the mycobacterial theory. The mycobacterial theory and the autoimmune theory are complementary; the first deals with the aetiology of the disorder, the second deals with its pathogenesis. Combined therapies directed against a mycobacterial aetiology and inflammation may be the optimal treatment of the disease.

Furazolidone combination therapies for Helicobacter pylori infection in the United States.

BACKGROUND: Antibiotic resistance has begun to impair the ability to cure Helicobacter pylori infection. AIM: To evaluate furazolidone as a component of combination therapies for treatment of H. pylori infection in the United States. METHODS: Patients with active H. pylori infection received furazolidone combination therapy for 14 days (furazolidone 100 mg and tetracycline 500 mg t.d.s.; omeprazole 20 mg o.d. in the morning and, depending on the pre-treatment antimicrobial susceptibility pattern, 500 mg of metronidazole or clarithromycin t.d.s.). RESULTS: A total of 27 patients received the metronidazole containing combination (cure rate 100%) and seven received the clarithromycin combination (cure rate 86%). Overall the cure rates for intention-to-treat was 97% (95% CI: 85% to 100%). The single failure took the clarithromycin containing combination for only 2 days (per protocol cure rate = 100%). Side-effects were common and led to discontinuation of therapy in 26% of patients. An attempt to eliminate metronidazole and clarithromycin and use furazolidone, tetracycline, and lansoprazole b.d. produced an unsatisfactory cure rate of 72%. CONCLUSION: Furazolidone combination therapy appears to be effective. Additional studies with different antimicrobial combinations and duration of therapy are warranted.

Clarithromycin, amoxycillin and H2-receptor antagonist therapy for Helicobacter pylori peptic ulcer disease in Korea.

BACKGROUND: Effective anti-Helicobacter pylori therapies with few side-effects are needed. We previously showed that the regimen of amoxycillin, clarithromycin and an H2-receptor antagonist was effective in the United States. The current study tested whether this therapy would also be successful in Korea. METHODS: Patients with gastric or duodenal ulcers received amoxycillin (750 mg t.d.s.) plus clarithromycin (500 mg t.d.s.) for 2 weeks and nizatidine 300 mg at bedtime for 6 weeks. Endoscopic examinations were performed before treatment and 4 or more weeks after ending antimicrobial therapy. H. pylori status was confirmed by rapid urease testing and histological examination of gastric antrum and corpus biopsies using the Genta stain. Antibiotic resistance was tested using the E-test method. Cure was defined as no evidence of H. pylori infection 4 or more weeks after ending therapy. RESULTS: Seventy-two patients (59 males and 13 females; mean age 46 years), including 35 with duodenal ulcers, 30 with gastric ulcers and seven with both, were studied. H. pylori infection was cured in 95.8% (69/72 patients; 95% CI = 88.3-99.1%). Two of the treatment failures had culture data and one had pre-treatment resistance to clarithromycin. Smoking did not have an adverse effect on therapy. Ten patients (15%) developed side-effects during treatment, but all were mild and did not require treatment interruption. No case of reinfection was noted during follow-up. CONCLUSION: The combination of amoxycillin, clarithromycin and an H2-receptor antagonist is effective in Korean patients with H. pylori infection.

Metronidazole containing quadruple therapy for infection with metronidazole resistant Helicobacter pylori: a prospective study.

BACKGROUND: Metronidazole remains a key component of H. pylori infection therapy. It has been suggested that despite resistance, metronidazole may be effective when given at high dose with bismuth, tetracycline, and a proton pump inhibitor (quadruple therapy). AIM: To prospectively evaluate metronidazole quadruple therapy for treatment of metronidazole resistant H. pylori infection in the United States. METHODS: Patients infected with metronidazole resistant H. pylori were prospectively prescribed 14 days of quadruple therapy consisting of metronidazole 500 mg t.d.s., tetracycline 500 mg q.d.s., two bismuth subsalicylate tablets q.d.s., and omeprazole 20 mg o.d. RESULTS: A total of 26 patients were entered into the study; 22 for their first treatment and four as re-treatment for failed therapy. Of the 26 patients, 24 were cured (cure rate 92%; 95% CI: 78-99%). Both treatment failures reported full compliance to 14 days of therapy. Side-effects were common and resulted in premature discontinuation of therapy in 31%. Premature discontinuation did not reduce the cure rate. CONCLUSION: Quadruple metronidazole combination therapy is effective despite the presence of metronidazole resistance and should be considered as either first line therapy or for failures of twice-a-day combination therapies.

Evaluation of gastric mucosal biopsy site and number for identification of Helicobacter pylori or intestinal metaplasia: role of the Sydney System.

Pathologists are frequently asked to evaluate gastric mucosal biopsy specimens for the presence of Helicobacter pylori infection and for potentially important changes such as intestinal metaplasia. No agreed-on system is both available and prospectively shown to provide reliable estimates of the underlying pathological condition. The Sydney System combined topographical, morphological, and causative information for evaluation of gastric biopsy specimens and provided recommendations regarding biopsy site and number. Both the biopsy sites and number were changed in 1994. Gastric biopsy specimens from patients who had multiple biopsies performed on predetermined sites were examined to compare the original and the revised Sydney Systems for the detection of intestinal metaplasia and H pylori. The diagnosis based on both versions of the Sydney System was then compared with that obtained by evaluating all specimens. Forty-six patients were studied, 20 with H pylori infection and 36 with intestinal metaplasia. Using either version of the Sydney System correctly categorized H pylori infection status in 100%. Both the original and the revised Sydney recommendations seriously underestimated the prevalence of intestinal metaplasia. Intestinal metaplasia was missed in more than 50% of those with confirmed intestinal metaplasia. No set or site of biopsy specimens was found that could reliably exclude the presence of intestinal metaplasia. Current and future studies that use the Sydney System as basis for detecting intestinal metaplasia are not likely to be reliable. Likewise, using the Sydney System to test posttherapy or with time will not accurately reflect the true status of intestinal metaplasia.

Histological features do not define NSAID-induced gastritis.

Nonsteroidal anti-inflammatory drug (NSAID) use is a common cause of peptic ulcer. This study investigated the nature, frequency, and topographic distribution of histological abnormalities of the gastric mucosa associated with chronic NSAID use. A set of 3 to 11 mapped gastric biopsy specimens were obtained from 108 chronic users of NSAIDs and 61 controls. Each specimen was graded from 0 to 3 for each of the following features: foveolar hyperplasia, smooth muscle fibers, edema, neutrophils, intestinal metaplasia, eosinophils, mononuclear cells, mucosal hemorrhage, atrophy, and Helicobacter pylori. We found that foveolar hyperplasia, considered one of the characteristic features of chemical gastropathy, was absent in 66% of NSAID users. Foveolar hyperplasia was present in 37 NSAID users (34%) and in 10 controls (18%); prominent smooth muscle fibers were found in 51 NSAID users (47%) and 10 of the controls (16%). Concurrent H pylori gastritis obscured the histopathologic changes of NSAID use. All other parameters, including H pylori infection rate (57% v 51%) were similar in NSAID users and controls. We conclude that the histological features characteristic of NSAID users were present only in a subset of patients. No single histological feature can be used to characterize or diagnose chemical gastropathy and no simple set of diagnostic criteria can be applied for this purpose.