Antimicrobial effectiveness of ketoconazole against metronidazole-resistant Helicobacter pylori isolates from Iranian dyspeptic patients.
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Biomedical subjects
Publications and source records attributed to S Massarrat.
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In a 65-year-old patient with ascites, jaundice and positive hepatitis B surface antigen (HBsAg), the histological diagnosis of cirrhosis with knodell total score 13 was made in 1995. The patient was followed up for 8 years. Spontaneous seroconversion of HBsAg appeared. Except for slight hyperbilirubinemia, all pathologic, clinical laboratory data remained normal from the second year of diagnosis till 8 years of follow-up. In the last follow up, the markers of liver fibrosis were all normal. The portal vein diameter was decreased and the esophageal varices disappeared. The imaging of liver by sonography and CT-scan did not reveal any abnormality.
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Helicobacter pylori infects the majority of the population in the developing countries. However, the rate of gastrointestinal complications such as peptic ulcers and gastric malignancies has no parallel with the infection. In order to determine whether cytotoxin (vacA) and its allelic polymorphism can serve as screening markers for such a population, H. pylori strains were isolated from one hundred and thirty two dyspeptic patients. H. pylori genomic DNA was extracted and underwent PCR-amplification for the cytotoxin alleles. Genotyping of the signal sequence region of the vacA gene identified 68% (70 out of 103) of patients with non ulcer dyspepsia (NUD) and 79% (23 out of 29) of the patients with peptic ulcer disease (PUD) possessing the s1 genotype. S1 strains were significantly more prevalent among patients with PUD as compared to the NUD (p < 0.05). In regard to the middle region, 55% of the patient isolates belonged to the m2 genotype with no correlation to disease. The s1m2 genotype was the most prevalent among all patients and significantly correlated with the PUD group (p < 0.05).
BACKGROUND: A definitive treatment for functional dyspepsia (FD), and the role of Helicobacter pylori eradication on the course of this disease are controversial. AIM: To investigate the effect of a combination of acid-suppressing and prokinetic drugs or eradication therapy on the course of H. pylori-positive FD. METHOD: A total of 157 patients with endoscopically-proven H. pylori-positive FD and no response to 4 weeks of antacid therapy were randomly divided into 2 groups. 84 were placed on bismuth subnitrate plus metronidazole and amoxicillin (group A) and 73 received ranitidine and metoclopramide for 4 weeks (group B). The severity of symptoms (7 items) were assessed on a 6-point categorical scale. Group B patients who failed to respond to their medication underwent eradication therapy after 3 months. All patients were followed and assessed for 9 months after the end of therapy by the same clinicians who initiated the therapy. RESULTS: At the end of the medication period, symptom's score decreased significantly, and to the same extent. At 3-month follow-up moderate or complete response was achieved in 27.4% (group A) and 19.2% (group B) by intention-to-treat analysis. 34 patients of group B, not responding to treatment, underwent eradication therapy and followed as group A. Eradication of H. pylori was successful in 60 of 110 controlled patients (54%). After 9-month follow-up, complete or moderate response was observed in only 30% of 60 patients in whom H. pylori had been eradicated (intention-to-treat analysis), compared to 38% in 50 noneradicated cases (p > 0.05, 95% CI: 19-43 vs. 24-52). CONCLUSION: Eradication therapy with bismuth compound is effective as ranitidine plus metoclopramide in a subgroup of patients with FD not responding to antacid therapy. There is no difference in improvement between patients cured or not cured from H. pylori infection. This suggests that bismuth compounds were effective in FD when used in the eradication regimen. Combination therapy with acid-suppressing drugs plus prokinetic and bismuth seems to hold promise for FD.
BACKGROUND: The eradication of Helicobacter pylori plays a pivotal role in the treatment of peptic ulcer disease. Metronidazole resistance, common in Iran, is claimed to be a major reason for the failure of metronidazole-containing regimens. Both clarithromycin and furazolidone are potential alternatives for metronidazole. AIM: To assess and compare the effectiveness of clarithromycin- and furazolidone-based regimens in eradicating H. pylori in a population with a high metronidazole resistance rate. METHODS: Patients with proven duodenal ulcer and H. pylori infection were randomly assigned to one of two groups. The patients received 2 weeks of omeprazole 20 mg b.d., amoxicillin 1000 mg b.d, bismuth subcitrate 240 mg b.d. and either clarithromycin 500 mg b.d. (the OABC group) or furazolidone 200 mg b.d. (the OABF group). RESULTS: A total of 118 patients were randomized, 55 in the OABC group and 63 in the OABF group. The intention-to-treat eradication rate was 84% and 85% for the OABF and OABC groups, respectively. The per protocol eradication rates were 90% for both groups. CONCLUSIONS: OABC and OABF are both effective in eradicating H. pylori in areas where metronidazole resistance is a problem. OABF is a good alternative in the face of growing resistance to clarithromycin in developed countries, and is attractive for developing countries where clarithromycin is not readily available.
BACKGROUND AND AIM: We sought to compare the efficacy and tolerability of an omeprazole/clarithromycin/bismuth/tetracycline-based quadruple therapy to that of a ranitidine/metronidazole/bismuth/tetracycline-based quadruple therapy of 2 or 3 weeks duration in a population with a high prevalence of metronidazole-resistant Helicobacter pylori and low triple therapy eradication rates. METHODS: Two hundred and twenty-one patients who presented endoscopically proven duodenal ulcers and a positive rapid urease test were randomized to receive either: (i) omeprazole 20 mg b.i.d., clarithromycin 250 mg b.i.d., bismuth subcitrate 240 mg b.i.d. and tetracycline 500 mg b.i.d (OCBT) for 2 weeks; (ii) ranitidine 300 mg b.i.d., metronidazole 500 mg b.i.d, bismuth subcitrate 240 mg b.i.d. and tetracycline 500 mg b.i.d. (RMBT2) for 2 weeks; or (iii) ranitidine 300 mg b.i.d., metronidazole 500 mg b.i.d, bismuth subcitrate 240 mg b.i.d. and tetracycline 500 mg b.i.d. (RMBT3) for 3 weeks. Patients were interviewed 2 weeks after the completion of therapy to review compliance and side-effects. Eradication of H. pylori was assessed 8 weeks after the completion of therapy with the use of a 14C-urea breath test. RESULTS: The per-protocol eradication rate was significantly higher with OCBT (88%) than RMBT2 (73%) or RMBT3 (71%) (P<0.05). The intent-to-treat eradication rate was numerically higher with OCBT (80%) than RMBT2 (68%) or RMBT3 (68%), although this difference did not reach statistical significance (P=0.09). Per-protocol or intent-to-treat eradication rates were similar with RMBT2 and RMBT3. There were significantly greater side-effects with the RMBT2 regimen. CONCLUSIONS: The omeprazole/clarithromycin/bismuth/tetracycline-based quadruple therapy provides higher H. pylori eradication rates than the ranitidine/metronidazole/bismuth/tetracycline-based quadruple therapy when administered per protocol. The prolongation of the latter regimen from 2 to 3 weeks did not increase eradication rates.
BACKGROUND: Prevalence of gallstone disease is different depending on the geographic region involved. Few studies, in Asia but not from Iran, about the frequency of gallstone disease have been published. The aim of this study is to examine the prevalence of gallstone disease in Iran. METHODS: Four hundred and seventy-seven nomads from southern Iran, 513 industrial laborers older than 34 years, and 421 laborers from a pharmaceutical company above 30 years of age, and 471 elderly persons from three nursing homes near Tehran underwent abdominal sonography. RESULTS: There were 1373 men and 509 women. Eighty-nine subjects had gallstone disease and 10.1% of them were cholecystectomized. While the prevalence in the men and women in the age group 31-40 years was very low (0.3% in men and 1.8% in women), it increases sharply in men older than 60 years and women older than 50 years to more than 10-fold (12.5 and 24.6% in male and female with an age 71-80 years, respectively). CONCLUSION: In Iran, gallstone disease is very uncommon in middle-aged people, but increases sharply in older people. However, this does not reach the high prevalence seen in Western countries. The intake of a high fiber-containing diet, a low number of overweight people, smoking habit and hyperlipidemia are probably the cause for this low prevalence.
INTRODUCTION: One of the most economical and effective therapeutic regimens for eradication of Helicobacter pylori is the classic triple therapy with amoxycillin or tetracycline, metronidazole and a bismuth derivative. Addition of H2-receptor antagonists to these drugs may heighten the rate of eradication and shorten the duration. We therefore performed a randomized controlled trial comparing twice daily metronidazole, bismuth derivative and amoxycillin for 2 weeks with additional ranitidine for 1 or 2 weeks. PATIENTS AND METHODS: In total, 240 adult patients with duodenal ulcer and H. pylori infection were randomly assigned to one of the following regimens: (1) amoxycillin 1 g bid, metronidazole 500 mg bid, bismuth sub-citrate 240 mg bid and ranitidine 300 mg bid for 1 week; (2) triple therapy without ranitidine for 2 weeks; or (3) triple therapy plus ranitidine 300 mg bid for 2 weeks. Side-effects of the drugs were evaluated two weeks after starting the treatment. The rapid urease test and histology from antrum and corpus, and/or 14C- urea breath test were used to determine H. pylori eradication six weeks after starting the treatment. RESULTS: In total, 195 patients were followed up for 6 weeks. The most frequent drug side-effects were unpleasant taste (46%), dry mouth (41%) and fatigue (26%), which had an equal distribution in all treatment groups. Endoscopy and 14C- urea breath test were performed for 178 and 123 patients, respectively. Eradication of H. pylori was documented in 19/64 (29.7%), 29/63 (46%) and 50/68 (73.5%) of patients in groups 1, 2 and 3, respectively (P < 0.000001 for group 1 versus group 3; P < 0.0014 for group 2 versus group 3; difference not significant for group 1 versus group 2). An intention-to-treat analysis showed eradication rates of 19/80 (23.75%), 29/80 (36.25%) and 50/80 (62.5%) for groups 1, 2 and 3, respectively. At four weeks post-treatment, the most sensitive test for evaluation of eradication of H. pylori was histology. CONCLUSION: Although combined use of an H2-receptor antagonist and twice daily triple therapy in a two-week regimen is more effective than two-week triple or one-week quadruple therapy in Iranian patients, none of these regimens is ideal in countries with a probable high rate of resistant and strongly toxic strains of H. pylori.
BACKGROUND/AIM: In developing countries the standard quadruple therapy containing metronidazole results in suboptimal eradication rates of Helicobacter pylori (<75%). In a retrospective study, we undertook to evaluate efficacy and tolerability of a furazolidone-based regimen (omeprazole, furazolidone, bismuth, and tetracycline) in patients who had previously failed the standard metronidazole-based regimen (omeprazole, metronidazole, bismuth, and amoxicillin). METHODS: The records of H. pylori infected patients who were referred to outpatient clinic (from March 1999 to August 1999) and who underwent previous eradication regimens were studied. A total of 320 cases were noted to have received a metronidazole-based quadruple regimen. From these 320 patients, 80 were noted to have failed this regimen based on a urea breath test. These 80 patients were enrolled in the study and given the furazolidone-based regimen. Side effects were assessed at follow-up visits. At least 2 months after the end of each therapy regimen, a (14)C-urea test was performed in each subject to document the cure of the patients. RESULTS: A total of 80 patients (39 males and 41 females) with a mean age of 43.8 +/- (SD) 13.3 years were studied. The H. pylori eradication rate was 90% with the furazolidone-based regimen. The side effects of this regimen were minor. CONCLUSIONS: A furazolidone-based regimen is effective in patients who do not achieve cure of H. pylori infection with the metronidazole-based quadruple therapy. In areas where the metronidazole resistance is high, initial therapy with a furazolidone-based regimen is recommended.
OBJECTIVE: Furazolidone, an old but cheap antibiotic, was shown to be a good alternative to metronidazole in triple therapy for Helicobacter pylori eradication in areas where metronidazole resistant bacteria are common, but randomized studies are lacking. AIM: A randomized controlled trial to determine the efficacy and safety of furazolidone compared to metronidazole in classic quadruple therapy for eradication of H. pylori infection in duodenal ulcer patients. METHODS: Patients with endoscopically proven duodenal ulcer and positive urease test were randomized to receive ranitidine 300 mg, amoxycillin 1000 mg and bismuth subcitrate 240 mg b.d, with either furazolidone 200 mg b.d (RABF), or metronidazole 500 mg b.d. (RABM) for 2 weeks. Compliance and side-effects were monitored and recorded by table diary. H. pylori eradication was assessed at least 4 weeks after the completion of therapy with 14C-urea breath test. RESULTS: A total of 106 patients were enrolled and 101 (59 male, 42 female, mean age=40 +/- 11 years) completed the study. Endoscopic findings and demographic data were comparable in both groups. Intention-to-treat eradication rates were 75% and 55% (P=0.03) and per protocol eradication rates were 82 and 56% (P=0. 006) in the RABF and RABM groups, respectively. Side-effects were reported by 13 patients (27%) in the RABF group (one stopped treatment) compared to five patients (10%) in the RABM group (P=0. 04). CONCLUSION: Quadruple therapy containing furazolidone, instead of metronidazole, results in a significantly higher H. pylori eradication rate in Iranian duodenal ulcer patients.
BACKGROUND: Classic triple therapy with bismuth, tetracycline and metronidazole is one of the most economic and effective regimens for the eradication of Helicobacter pylori. The aim of the study was to assess the efficacy of two different doses of tetracycline (TET) and metronidazole (MET) on cure of H. pylori infection and its MET-resistant strains. MATERIAL AND METHODS: A total of 131 patients with duodenal ulcer were randomized into three groups and received the following medication for 2 weeks: group A, colloidal bismuth subcitrate (CBS) 3 x 120 mg + TET 3 x 500 mg + MET 3 x 250 mg/day; group B, CBS 3 x 120 mg + TET 3 x 500 mg + MET 3 x 125 mg/day; group C, CBS 3 x 120 mg + TET 3 x 250 mg + MET 3 x 125 mg/day. Control endoscopy was performed after 6 weeks. Two biopsy specimens from antral and three from corpus mucosa were taken for a urease test, histology and culture. Eradication was concluded if all three tests were negative for H. pylori. MET resistance was determined by the disc diffusion method. RESULTS: In total, 121 patients completed the study. Only two of the 43 patients in group A discontinued the therapy due to intolerance. Cure of H. pylori infection was achieved by per protocol analysis in 33 of 43 patients in group A (76.7%), in 20 of 40 patients in group B (50%) and in 20 of 38 patients in group C (52.6%) (P < 0.05 for A versus B or C). Forty-two out of 112 patients had H. pylori strains resistant to MET (42%). In each group, the cure rate of infection was higher in patients with MET-sensitive H. pylori than in MET-resistant H. pylori (80.7% versus 64.2% in group A, 60% versus 38.8% in group B and 52.6% versus 40% in group C, respectively). Increase of MET dose from 375 mg (in groups B and C) to 750 mg/day (in group A) seems to augment the eradication of MET-sensitive as well as MET-resistant strains (up from 52% to 84% and from 39% to 64%, respectively; P < 0.05). CONCLUSION: Cure rate of H. pylori infection under classic triple therapy remains unaffected by dose reduction of tetracycline but not of metronidazole. In countries with a high prevalence of metronidazole resistance, such as Iran, higher doses of metronidazole are probably needed to increase the cure rate of bismuth triple therapy.
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OBJECTIVE: To determine the speed of the healing process of duodenal ulcers during eradication regimens with and without a high-dose anti-secretory drug. SETTING: An outpatient department of a university hospital as a community-based and referral centre. MATERIALS: A total of 101 patients with proven duodenal ulcer and a positive urease test were randomized into two groups: one group received the classic triple therapy (bismuth subnitrate 3 x 375 mg for 4 weeks + tetracycline 3 x 500 mg + metronidazole 3 x 250 mg daily, both for 2 weeks ), the other group received dual therapy comprising amoxicillin 2 x 1000 mg + omeprazole 2 x 20 mg daily, both for 2 weeks. All patients underwent a control endoscopy 2 and 6 weeks after the beginning of treatment. Eradication was assumed if a urease test and culture were negative in all specimens taken from antral and corpus mucosa. RESULTS: In total, 93 patients completed all 6 weeks of the study (45 patients in the triple therapy group and 48 patients in the dual therapy group). The disappearance of ulcer pain was faster in the group under the regimen including omeprazole (dual therapy) than in the group with triple therapy (2.4+/-2.7 days versus 4.5+/-3.5 days; P< 0.01). The two-week healing rate was significantly higher in the patients treated with dual therapy than in the group treated with triple therapy (77% versus 33.3%; P< 0.01); however, 12 out of 37 patients with a healed ulcer in the dual therapy group had an ulcer relapse at 6 weeks (six became symptomatic). Only in one of these 12 patients was Helicobacter pylori eradicated. Fifteen of the 45 patients with triple therapy had healed ulcers at 2 weeks, and of these 14 remained healed at 6 weeks (H. pylori was eradicated in eight patients). The six-week healing rate with dual therapy was the same as with classic triple therapy (64.6% versus 77.6%); the eradication rate was lower in the former group than in the latter (30.4% versus 51.1% respectively; P=0.056). CONCLUSION: A high dose of a proton pump inhibitor (PPI) combined with amoxicillin results in rapid ulcer healing and pain disappearance, but is associated with early ulcer relapse due to lack of eradication of H. pylori. Its addition to regimens with bismuth and antibiotics is not necessary to achieve ulcer healing.
In almost all eradication regimens, which contain antibiotics and bismuth derivatives, the administration of acid suppressing drugs for 4-6 weeks is recommended for healing of duodenal ulcer. The aim of this multicenter double blind study is to elucidate the effect of two classic antibiotics tetracycline (CAS 60-54-8) and metronidazole (CAS 443-48-1) alone or combined with ranitidine (CAS 66357-35-5) on the healing of duodenal ulcer and eradication of Helicobacter Pylori. Patients with duodenal ulcer were randomized to two treatment groups: group A received either ranitidine 4 x 150 mg or tetracycline 4 x 500 mg or metronidazole 3 x 250 mg for 2 weeks. Group B received 4 x placebo + tetracycline and metronidazole as in group A for 2 weeks. A final endoscopy was performed after 8 weeks. Four biopsy specimens were obtained from the antrum (two) and corpus (two) for both urease test and hematoxylin stain for detection of H. pylori. Out of 201 patients entering the study 156 completed the study (78 in A and 78 in B). The healing rate of duodenal ulcer was 98.7% in group A and 97.5 in group B. The eradication rate was only 33.3% in group B but 64% in group A (p < 0.001), when additionally ranitidine was given. The present study shows that treatment with the two antibiotics tetracycline and metronidazole alone results in a very low H. pylori eradication, but almost complete healing of duodenal ulcer after 8 weeks. Prolonged administration of antisecretory drugs in eradication regimens containing two antibiotics is not necessary for duodenal ulcer healing. However, the addition of H2-receptor antagonists or proton pump inhibitors to antibiotics increases the eradication rate.
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OBJECTIVE: To determine the prevalence of peptic ulcer disease, irritable bowel syndrome (IBS) and chronic constipation in two Iranian populations (pastoral nomads and industrial labourers) with different life styles, and to evaluate the risk factors associated with these diseases. SUBJECTS: A total of 455 randomly selected pastoral nomads and 492 industrial labourers (all male) aged between 35-55 years. METHODS: Demographic and social data were obtained by interviews. An upper gastrointestinal tract endoscopy was performed and biopsy specimens were taken from subjects complaining of abdominal symptoms and randomly selected asymptomatic subjects. A urease test was performed on antral specimens. Serum pepsinogen I concentrations and Helicobacter pylori antibody titres were measured by radioimmunoassay and immunoglobulin (Ig) G enzyme-linked immunosorbent assay tests, respectively. RESULTS: Serum pepsinogen I concentrations were similar in both nomads and industrial labourers, and the percentage with positive antibody titres for H. pylori was high in both populations (86.3 and 91% in nomads and industrial labourers, respectively). Industrial labourers were twice as likely to have duodenal ulcer (P < 0.05) than nomads. The prevalence of duodenal ulcer disease and gastric ulcer was 4.6 and 0.6% in nomads and 10.3 and 0.4% in industrial labourers, respectively. The prevalence of IBS was similar in nomads (3.1%) and industrial labourers (3.6%). Fewer nomads (1.4%) than industrial labourers (3.3%) had chronic constipation. Logistic regression analysis showed that being an industrial labourer, or smoker and having undergone previous non-gastric surgery were risk factors for duodenal ulcer disease. When the variable 'urease test' was included in the logistic regression analysis, smoking, a positive urease test and the quantity of fruit eaten per week were associated risk factors. The risk factors associated with IBS were the use of analgesics and back pain. The only risk factor associated with chronic constipation was being an industrial labourer. CONCLUSIONS: Industrial labourers were twice as likely to have duodenal ulcer disease as nomads. The prevalence of IBS and chronic constipation in the two male Iranian populations was lower than that found in western countries. Duodenal ulcer disease was associated with H. pylori colonization but not with a positive serum antibody titre for H. pylori. H. pylori colonization of the antral mucosa and smoking are causative factors for duodenal ulcer disease and fruit intake is possibly an associated factor.