Asghar Qasim

Treatment of Helicobacter pylori Infection

This article aims to examine current best practice in the field reference to first‐line, second‐line, rescue and emerging treatment regimens for Helicobater pylori eradication. The recommended first‐line treatment in published guidelines in Europe and North American is proton pump inhibitor combined with amoxicillin and clarithromycin being the favoured regimen. Rates of eradication with this regimen however are falling alarmingly due to a combination of antibiotic resistance and poor compliance with therapy. Bismuth based quadruple therapies and levofloxacin based regimes have been shown to be effective second line regimens. Third‐line options include regimes based on rifabutin or furazolidone, but susceptibility testing is the most rational option here, but is currently not used widely enough. Sequential therapy is promising but needs further study and validation outside of Italy. Although the success of first line treatments is falling, if compliance is good and a clear treatment paradigm adhered to, almost universal eradication rates can still be achieved. If compliance is not achievable, the problem of antibiotic resistance will continue to beset any combination of drugs used for H. pylori eradication.

Rifabutin- and furazolidone-based Helicobacter pylori eradication therapies after failure of standard first- and second-line eradication attempts in dyspepsia patients

Background : Optimal management approach is not well defined for subjects who fail initial first‐ and second‐line Helicobacter pylori eradication attempts and are dealt on a case‐by‐case basis by the specialists.

Treatment of Helicobacter pylori infection and factors influencing eradication

Currently available Helicobacter pylori eradication therapies are considered very effective and safe. The most recent eradication guidelines proposed in the Maastricht 2‐2000 Consensus Report recommend the use of proton pump inhibitors (standard b.d.) along with clarithromycin (500 mg b.d.) and amoxycillin (1000 mg b.d.) or metronidazole (500 mg b.d.) for a minimum of 7 days. The combination of amoxycillin and clarithromycin is preferred because it may favour best results with a second‐line proton pump inhibitor quadruple therapy. The recommended second‐line therapy includes a combination of a proton pump inhibitor (standard b.d.) with bismuth salt (subsalicylate/subcitrate 120 mg q.d.s.), metronidazole (500 mg t.d.s.), and tetracycline (500 mg q.d.s.) for a minimum of 7 days. Extended proton pump inhibitor‐based triple therapy can be used if bismuth is not available. Specialists should manage subsequent failures. Based on direct and indirect evidence from well‐designed studies and clinical experience, eradication is recommended in gastric and duodenal ulcers, MALToma, atrophic gastritis, postgastric cancer resection, and in first‐degree relatives of gastric cancer patients. The most common reason for treatment failure is poor compliance with eradication guidelines. Antibiotic resistance may be a significant factor in certain geographical areas. Proton pump inhibitors are an integral part of the eradication regimens as proved by meta‐analyses of clinical trials. Novel agents used in secondary failure are few and depend on the use of new antibiotics. The role of H. pylori‐specific antibiotics, probiotics, and vaccines is not established as yet. Widespread acceptance of the eradication guidelines should be regarded as the single most important factor in eradication success.

Coeliac disease in Europe

Coeliac disease is a condition predominantly of the small bowel, resulting from sensitivity to ingested gluten, a protein found in wheat, barley and rye. Coeliac disease may be present in approximately 1 in 150–300 Europeans, yet it remains underdiagnosed in most countries. Coeliac disease as a clinical entity has been recognized for many years. As far back as the second century AD, Aretaeus from Cappadocia described what is believed to be the first report of a gastrointestinal condition resembling coeliac disease when he outlined a chronic wasting illness associated with diarrhoea. The first detailed description of the ‘coeliac affection’ was in 1888 by Samuel Gee, a paediatrician in St Bartholomew’s Hospital, London, who was also the first to propose dietary manipulation as the mainstay of treatment. However, his diets were quite restrictive, and although patients improved, few could be prevailed upon to endure the regimen for long. During World War II, food shortages, in particular of cereal, led Dicke, a Dutch paediatrician, to the conclusion that a ‘wheat factor’ led to coeliac disease. Affected children thrived when cereal was in short supply and deteriorated once the products became widely available again.

Helicobacter pylori resistance to metronidazole and clarithromycin in Ireland.

Introduction Helicobacter pylori eradication rates have fallen considerably in recent years. Antibiotic resistance is thought to be rising. Objectives To examine the levels of resistance to metronidazole (MTZ) and clarithromycin (CLA) in H. pylori, isolates were taken in a reference centre in Ireland from 2007 to 2008 and were compared to a similar cohort from a study in 1997. Method Antimicrobial susceptibilities were tested by E-test. Frequencies of spontaneous metronidazole and clarithromycin resistance were measured on an agar plate containing the antibiotics at concentrations of 2× and 4× minimum inhibition concentration values. Clinical data were obtained from charts, laboratory and endoscopy reports. Results Two hundred and twenty-two patients were analyzed, 98 were females. Colonies amenable to culture were grown in 219 patients. Thirty-seven had prior attempts at eradication therapy (all with amoxicillin–CLA–proton pump inhibitor. A total of 31.5% of the patients had strains resistant to MTZ and 13.2% of the patients were noted to have strains resistant to CLA. About 8.6% of the patients had strains resistant to both the agents. CLA resistance was 9.3% in those who had no prior eradication therapy compared with 32.4% of those who had. CLA resistance increased from 3.9%, among treatment-naive patients in 1997, to 9.3% in our study. MTZ resistance was 29.1% in the treatment-naive population. In 1997, MTZ resistance in the treatment-naive cohort was 27.1%. MTZ resistance was more likely to occur in females (35.4 vs. 28.5%) than in males. Conclusion This study shows that resistance to CLA among Irish patients infected with H. pylori has increased since 1997. The future of treatment may well lie in the widespread use of sensitivity testing before the treatment. This would promote an accurate treatment.

Analysis of drug resistance and virulence-factor genotype of Irish Helicobacter pylori strains: is there any relationship between resistance to metronidazole and cagA status?

Background  Helicobacter pylori infection is eradicated with antimicrobial agents and drug‐resistant strains make successful treatment difficult. Geographical variations in virulence‐factor genotype also exist.

Efficacy and safety of 6-thioguanine in the management of inflammatory bowel disease

Objective. 6-thioguanine has been used as an alternative immunomodulator in the treatment of inflammatory bowel disease but data on its efficacy and safety are limited. The aim of this study was to analyse our experience of the efficacy and safety of 6-thioguanine in inflammatory bowel disease. Material and methods. Patients attending the inflammatory bowel disease clinic who were started on 6-thioguanine therapy were included in this prospective observational study. Indications for initiating 6-thioguanine therapy and other related clinical, pharmacological and laboratory parameters prior to and during therapy were recorded to determine the efficacy and safety of 6-thioguanine. Results. A total of 40 patients were treated with 6-thioguanine, 28 with Crohns disease, 10 with ulcerative colitis and 2 with indeterminate colitis, at a fixed daily dose of 40 mg and continued for a median duration of 34 weeks (range 2–90 weeks). The indications for 6-thioguanine therapy included previous clinical resistance to thiopurine analogues (n=21), intolerance to thiopurine analogues (n=8) and de novo 6-thioguanine use in steroid refractory disease (n=11). Disease remission was reached in 44%, 73% and 89% of these patient groups at 3, 6 and 12 months, respectively. Inflammatory markers and steroid use were significantly lower during 6-thioguanine therapy compared with in the period before therapy. Therapy was discontinued in 13 patients (33%), mainly because of thrombocytopenia and associated hepatotoxicity. Conclusions. 6-thioguanine is a useful addition to treatment in inflammatory bowel disease but the frequent occurrence of hepatotoxicity limits its routine use.

Helicobacter pylori eradication: role of individual therapy constituents and therapy duration.

Treatment of Helicobacter pylori (H. pylori) infection has become a key factor in the management of dyspepsia and is the treatment of choice for peptic ulcer disease. First‐line eradication regimens combining a proton pump inhibitor (PPI) with clarithromycin and amoxicillin or metronidazole are considered most effective when given for a minimum period of 1 week. Eradication regimens of shorter duration have shown promising results but clinical experience remains limited. Pharmacological properties such as bioavailability and plasma concentrations of individual PPIs differ between individuals but it remains unclear whether these differences impact on the efficacy of eradication therapy and are influenced by renal or hepatic impairment. Bioavailability of PPIs also differs and is impacted on by factors including intragastric pH, metabolic pathways, potency on an mg‐for‐mg basis and intrinsic antibacterial activity. Several significant pharmacokinetic differences between the PPIs do not seem to influence overall H. pylori eradication rates for first‐line triple therapy. However, comparison of factors including pharmacokinetics and treatment duration may prove important in achieving successful eradication with second‐ and third‐line treatments. Based on the factors which influence therapy outcome, we suggest an algorithm for the use of H. pylori eradication therapies.

Pylera® for the eradication of Helicobacter pylori infection

An ideal antibiotic regimen for Helicobacter pylori should achieve eradication rates of approximately 90%. Current 7-day triple therapy is successful in about two-thirds of patients. A novel treatment is required to achieve higher eradication with minimal induction of bacterial resistance. The aim of this article is to evaluate the safety and efficacy of a single triple capsule (Pylera®) containing bismuth, metronidazole and tetracycline, given with omeprazole for the eradication of H. pylori infection. Extensive literature searches were conducted using PubMed data from 1982 to 2007. This search included headings of H. pylori, bismuth and eradication therapy. The triple capsule Pylera, when given with omeprazole, achieved eradication rates ranging between 84 and 97%. Eradication rates were similar for clarithromycin- and metronidazole-resistant strains. Eradication rates with an omeprazole, bismuth, metronidazole and tetracycline regimen appeared comparable for metronidazole-resistant and -sensitive strains. This effect is not seen with the use of triple therapy in cases of clarithromycin resistance. Clinical trials did not report any serious side effects from bismuth-based regimens and compliance was similar to standard triple therapy. Bismuth-based triple therapy using Pylera is a simplified, effective and well-tolerated regimen achieving cure rates of above 90%.

Primary prevention of colorectal cancer: are we closer to reality?

Colorectal cancer is one of the leading causes of morbidity and mortality worldwide. An early detection of colorectal cancer determines therapeutic outcomes, while primary prevention remains a challenge. Our aim was to review the dietary, geographical and genetic factors in the causation and their possible role in the primary prevention of colorectal cancer. Data from experimental and clinical studies and population screening programmes were analysed to determine the factors responsible for causation of colorectal cancer. The role of dietary constituents, including the consumption of fat, red meat, fibre content, alcohol consumption, and other lifestyle issues, including obesity, lack of exercise and geographical variations in cancer prevalence were reviewed. The role of genetic and lifestyle factors in causation of colorectal cancer is evident from the experimental, clinical and population-based studies. Dietary factors, including the consumption of fat, fibre, red meat and alcohol, seem to have a significant influence in this regard. The role of micronutrients, vitamins, calcium may be relevant but remain largely unclear. In conclusion, there is ample evidence favouring the role of various dietary and lifestyle factors in the aetiology of colorectal cancer. Modification of these factors is an attractive option, which is likely to help in the primary prevention and reduced disease burden.