Review article: antibiotics and the gut

Antibiotics have an important place in the management of gastrointestinal disease. Recent studies have demonstrated efficacy in acute bacterial gastroenteritis caused by salmonellae and campylobacteriaceae, shigellae and enterotoxigenic strains of E coli (ETEC). Tetracycline remains effective in cholera. Antibiotic resistance is widespread amongst the enteric pathogens and can quickly spread during epidemics of infective diarrhoeas. It is important that antibiotics are reserved for the treatment of serious infections lest their effectiveness in these conditions be lost. Campylobacter pylori appears to be an important cause of chronic active gastritis and is amenable to treatment with antibiotics and bismuth salts. The role of C. pylori in the pathogenesis of peptic ulcer disease is not yet established but there is mounting evidence that antibiotic treatment will have a place in the treatment of this common condition. The effect of antibiotics on the normal intestinal microflora can have serious consequences. It is a major cause of resistance in urinary tract pathogens, can result in outbreaks of hospital infection with resistant organisms and frequently results in C. difficile associated diarrhoea.     

Review article: orthograde gut lavage for colonoscopy

Most colon cleansing regimens for surgical and diagnostic procedures such as colonoscopy are modifications of older barium enema X-ray preparations which have evolved in gastrointestinal laboratories influenced by empiric experience. Recent formal study allows for careful comparison of gut lavage, diet and cathartic, and oral sodium phosphate preparations. This review will evaluate oral lavage solutions and address their safety, tolerance and efficacy. Administration options are discussed as well as other diet and cathartic methods previously referred to as ‘standard preps’.     

Review article: the treatment of functional abdominal bloating and distension

Aliment Pharmacol Ther 2011; 33: 1071–1086

Summary

Background Abdominal bloating and distension are common symptoms in patients with functional gastrointestinal disorders (FGIDs), however, relatively little is known about their treatment. Aim To review the treatment trials for abdominal bloating and distension. Methods A literature review in Medline for English‐language publications through February 2010 of randomised, controlled treatment trials in adults. Study quality was assessed according to Jadad’s score. Results Of the 89 studies reviewed, 18% evaluated patients with functional dyspepsia, 61% with irritable bowel syndrome (IBS), 10% with chronic constipation and 10% with other FGIDs. No studies were conducted in patients diagnosed with functional abdominal bloating. The majority of trials investigated the efficacy of prokinetics or probiotics, although studies are heterogeneous with respect to diagnostic criteria and outcome measures. In general, bloating and/or distension were evaluated as secondary endpoints or as individual symptoms as part of a composite score rather than as primary endpoints. A greater proportion of IBS patients with constipation reported improvement in bloating with tegaserod vs. placebo (51% vs. 40%, P < 0.0001) and lubiprostone (P < 0.001). A greater proportion of nonconstipating IBS patients reported adequate relief of bloating with rifaximin vs. placebo (40% vs. 30%, P < 0.001). Bloating was significantly reduced with the probiotics, Bifidobacterium infantis 35624 (1 × 10⁸ dose vs. placebo: ?0.71 vs. ?0.44, P < 0.05) and B. animalis (live vs. heat‐killed: ?0.56 ± 1.01 vs. ?0.31 ± 0.87, P = 0.03). Conclusions Prokinetics, lubiprostone, antibiotics and probiotics demonstrate efficacy for the treatment of bloating and/or distension in certain FGIDs, but other agents have either not been studied adequately or have shown conflicting results.

     

Review article: metronidazole and the anaerobic gut flora

Metronidazole is a nitro-imidazole drug which was discovered nearly 30 years ago. Metronidazole has remained the mainstay of anti-anaerobic therapy following a change observation that its activity included anaerobic organisms. The predominant human reservoir of these anaerobic organisms is the gastrointestinal tract. In this review, the anaerobic flora and their pathogenic potential are described. The main characteristics of metronidazole and the role of selective decontamination of the gastrointestinal tract are also discussed.     

Review article: non-steroidal anti-inflammatory drugs and Helicobacter pylori

Non-steroidal anti-inflammatory drugs (NSAIDs) and Helicobacter pylori are well-recognized causes of gastroduodenal mucosal damage. This damage is mediated through the effects of both agents on acid secretion, neutrophil activity and function, and prosta- glandin metabolism. Clinical trials on the interrelation- ship between H. pylori, NSAIDs and gastroduodenal mucosal injury have yielded conflicting results. No consensus has been reached on what recommenda- tions should be implemented with regard to H. pylori eradication in patients on long-term NSAID therapy. At present, the presence of H. pylori is identified at endoscopy and eradication is carried out in symptomatic patients. Asymptomatic patients remain a dilemma that requires further investigation. Clinical practice will continue to be tailored to a patient's individual requirements. Therefore, in patients at risk of gastrointestinal haemorrhage, and on NSAID therapy, acid suppression therapy should be prescribed.     

Review article: over-the-counter drugs and the gastrointestinal tract

An increasing number of drugs are becoming available over-the-counter, empowering patients to treat them- selves. Although drugs presently available over-the-counter are generally safe, there are issues of safety and possible delays in diagnosis of serious conditions. Therefore it is vital that patients are made aware of the indications and limitations of over-the-counter drugs through improved communication and education. Pharmacists and drug companies will have an increasingly important role in giving information and advice to patients. This review looks at the present and future of over-the-counter medication, highlighting the safety aspects.     

Review article: abdominal bloating and distension in functional gastrointestinal disorders--epidemiology and exploration of possible mechanisms

Background A sensation of abdominal bloating, sometimes accompanied by an increase in girth (distension), is one of the most common and most intrusive features of functional bowel disorders. Aim To conduct a systematic, evidence‐based review of the epidemiology and pathophysiology of abdominal bloating and its relationship to distension. Methods The terms bloating, distension, functional bowel, irritable bowel syndrome, constipation and diarrhoea were searched on MEDLINE up to 2006. References from selected articles and relevant abstracts were also included. Results Approximately 50% of irritable bowel syndrome patients with bloating also experience an increase in abdominal girth and this is more pronounced with constipation than diarrhoea. Bloating appears to be more frequently associated with visceral hypersensitivity, whereas distension is more often related to hyposensitivity and delayed transit. Although there is little evidence for excessive gas as a cause of bloating, gas infusion studies suggest that handling of gas may be impaired in irritable bowel syndrome and there may also be abnormal relaxation of the anterior abdominal musculature in these patients. Conclusions There is unlikely to be a single cause for bloating and distension, which probably have different, but overlapping, pathophysiological mechanisms. Relieving constipation might help distension, but the treatment of bloating may need more complex approaches involving sensory modulation.     

Review article: mechanisms of initiation and perpetuation of gut inflammation by stress

Inflammatory bowel disease involves an interaction between genetic susceptibility, a host mucosal immune response and the enteric flora. However, the relapsing and remitting course underlines the importance of other modifiers, such as psychological stress. Doctors and patients share the view that stress plays a role in the initiation and perpetuation of disease. Levels of chronic perceived stress have been shown to correlate with symptom relapse and mucosal appearance, and stress management therapy has been shown to be beneficial. Animal models provide further evidence that stress may play a role in disease initiation and reactivation. Elucidation of the gut-brain-immune axis has provided insight into the mechanisms by which stress may result in gut inflammation. Stress can alter intestinal physiological function. Stress can increase gut permeability, increase ion secretion by a mechanism involving neural stimulation or mast cells, increase mucin release and deplete goblet cells. Stress causes parasympathetic activation via a mechanism involving corticotropin releasing factor, ultimately affecting mucosal mast cells. Stress also results in increased bacterial adherence and decreased luminal lactobacilli. As a result of all these changes luminal antigens may gain access to the epithelium, causing inflammation.     

Review article: clinical pharmacology models of irritable bowel syndrome

This review describes the basis for development of clinical pharmacology models of irritable bowel syndrome (IBS) and presents a critical analysis of current models. IBS is becoming a more circumscribed diagnosis by improved symptom criteria and this is perceived as helpful progress for the development of suitable models. Concepts about the aetiopathogenesis and pathophysiology of IBS are also evolving. Different models have been established to study specific derangements in motor function, visceral reflexes and conscious perception of gut stimuli. The review also focuses on specific examples of drug evaluation using appropriate and validated models.     

Review article: promotility drugs in the treatment of gastro-oesophageal reflux disease

Prokinetic agents are drugs that increase contractile force and accelerate intraluminal transit. They are often used in treating disorders of gastrointestinal motility including gastro-oesophageal reflux disease (GERD). The most widely studied agents include bethanechol, metoclopramide, domperidone and cisapride. These drugs act either by enhancing the effect of acetylcholine or by blocking the effect of an inhibitory neurotransmitter such as dopamine. With the exception of cisapride, the clinical efficacy of the various prokinetic agents in treating GERD has not been confirmed consistently. These agents have variable effects on oesophageal and gastric motor function and are fraught with side-effects. They are effective in relieving mild reflux symptoms but do not predictably heal oesophagitis. On the other hand, cisapride is thus far the most effective prokinetic agent studied for the treatment of GERD. It relieves reflux symptoms and promotes healing of grade I–II oesophagitis, with few side-effects or tachyphylaxis. Its most important role may be in the maintenance treatment of GERD either as a single agent or in combination therapy with an H₂-antagonist after oesophagitis healing.     

Review article: the evaluation of solitary liver masses

Background The increasing use of imaging modalities has led to the detection of more liver masses. The differential diagnosis of a focal liver mass includes a host of benign as well as malignant conditions. Aim To provide a comprehensive review on the commonly encountered liver masses, and to help guide an approach to their evaluation and management. Methods Pertinent literature that was identified through PubMed search and senior author’s experience formed the basis of this review. Results While most incidentally noted liver masses are benign, it may be difficult to differentiate them from those that are malignant. Furthermore, some benign lesions have malignant potential. Certain lesions such as focal nodular hyperplasia, haemangiomas and focal steatosis are often distinctly diagnosed by an imaging modality alone. The less frequently encountered hepatic adenomas are diagnosed radiologically in those with the appropriate clinical background and the absence of radiological features to suggest haemangioma or focal nodular hyperplasia. Conclusions A reasonable approach to the diagnosis, follow‐up and management of liver masses is based on a rudimentary knowledge of their presentation, associated clinical and laboratory features, natural history and available treatment options. Most often, the so called ‘incidentalomas’ are benign and require patient reassurance.     

Review article: the role of non-biological drugs in refractory inflammatory bowel disease

Background Up to one‐third of patients with inflammatory bowel disease (IBD) do not respond to, or are intolerant of conventional immunosuppressive drugs. Although biological agents are alternative treatments, they may not be suitable or available to some patients. Aim To review the evidence for use of nonbiological drugs in the treatment of patients with IBD refractory to corticosteroids or thiopurines. Methods A literature search was performed using PubMed for English language publications with predetermined search criteria to identify relevant studies. Results Published evidence from uncontrolled series and controlled clinical trials has been used to produce a practical approach relevant to clinical practice which incorporates the indication, optimal dose, and side effects of various therapies including tacrolimus, methotrexate, thalidomide, tioguanine, mycophenolate mofotil, leucocyte apheresis, nutritional therapy, antibiotics, probiotics, allopurinol, rectal acetarsol and ciclosporin in the treatment of patients with refractory ulcerative colitis and Crohn’s disease. Approaches to optimise thiopurine efficacy are also discussed. Conclusions Patients with IBD refractory to corticosteroids or thiopurines may respond to alternative anti‐inflammatory chemical molecules, but the evidence base for many of these alternatives is limited and further trials are needed.