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Carmelo Scarpignato

Publications and source records attributed to Carmelo Scarpignato.

13 recordsLinked to original sources
PubMed2006

Experimental and clinical pharmacology of rifaximin, a gastrointestinal selective antibiotic.

Rifaximin (4-deoxy-4'-methylpyrido[1',2'-1,2]imidazo [5,4-c]rifamycin SV) is a product of synthesis experiments designed to modify the parent compound, rifamycin, in order to achieve low gastrointestinal (GI) absorption while retaining good antibacterial activity. Both experimental and clinical pharmacology clearly show that this compound is a non-systemic antibiotic with a broad spectrum of antibacterial action covering Gram-positive and Gram-negative organisms, both aerobes and anaerobes. Being virtually non-absorbed, its bioavailability within the GI tract is rather high with intraluminal and fecal drug concentrations that largely exceed the minimum inhibitory concentration values observed in vitro against a wide range of pathogenic organisms. The GI tract represents therefore the primary therapeutic target and GI infections the main indication. This antibiotic has therefore little value outside the enteric area and this will minimize both antimicrobial resistance and systemic adverse events. Indeed, the drug proved to be safe in all patient populations, including young children. The appreciation of the pathogenic role of gut bacteria in several organic and functional GI diseases has increasingly broadened its clinical use, which is now extended to hepatic encephalopathy, small intestine bacterial overgrowth, inflammatory bowel disease and colonic diverticular disease.

Animals↗
PubMed2006

Treatment of functional bowel disorders: is there room for antibiotics?

Small bowel bacterial overgrowth is a syndrome associated with a broad range of predisposing conditions, characterized by the presence of pathological amounts or types of bacteria at the level of the small bowel, clinically evident with a spectrum of symptoms such as diarrhea, flatulence, abdominal pain and bloating. Some of these symptoms are very common complaints in patients suffering from functional bowel disorders (FBDs). Although the pathophysiological mechanisms responsible for FBDs are certainly multifactorial and not yet completely understood, several pieces of evidence suggest that an increased metabolic activity of intestinal bacteria is responsible for gas-related intestinal symptoms in a large subgroup of patients. In addition, byproducts of colonic fermentation might be able to trigger symptoms in those patients displaying visceral hypersensitivity. Targeting enteric bacteria with antibiotics therefore represents a logical approach to FBDs. Although systemic antimicrobials have been mostly used in the past, the availability of poorly absorbed antibiotics like rifaximin, being safe and effective, has represented a step forward in the treatment of this challenging clinical condition.

Anti-Bacterial Agents↗
PubMed2006

Management of colonic diverticular disease.

Diverticular disease of the colon is a complex syndrome that includes several clinical conditions, each needing different therapeutic strategies. In patients with asymptomatic diverticulosis, only a fiber-rich diet can be recommended in an attempt to reduce intraluminal pressure and slow down the worsening of the disease. Fiber supplementation is also indicated in symptomatic diverticulosis in order to get symptom relief and prevent acute diverticulitis. In this regard, the best results have been obtained by combination of soluble fiber, like glucomannan, and poorly absorbed antibiotics, like rifaximin, given 7-10 days every month. For uncomplicated diverticulitis the standard therapy is liquid diet and oral antimicrobials, usually ciprofloxacin and metronidazole. Hospitalization, bowel rest, and intravenous antibacterial agents are mandatory for complicated diverticulitis. Haemorrhage is usually a self-limited event but may require endoscopic or surgical treatment. Once in remission, continuous fiber intake and intermittent course of rifaximin may improve symptoms and reduce diverticulitis recurrence. These preventive strategies will likely improve patients' quality of life and reduce management costs. A surgical approach in diverticular disease is needed in 15-30% of cases and consists of removing the intestinal segment affected by diverticula. It is indicated in diffuse peritonitis, abscesses, fistulas, stenosis and after the second to fourth attack of uncomplicated diverticulitis. Young people and immunocompromised patients are more likely to be operated.

Colectomy↗
PubMed2006

Eradication of Helicobacter pylori: are rifaximin-based regimens effective?

Rifaximin is a non-absorbed semisynthetic rifamycin derivative with a broad spectrum of antibacterial activity including Gram-positive and Gram-negative bacteria, both aerobes and anaerobes. Although originally developed for the treatment of infectious diarrhea, the appreciation of the pathogenic role of gut bacteria in several organic and functional gastrointestinal diseases has increasingly broadened its clinical use. Being the antibiotic active against Helicobacter pylori, even towards clarithromycin-resistant strain, and being the primary resistance very rare, several investigations explored its potential use for eradication of the microorganism. Rifaximin alone proved to be effective, but even the highest dose (1,200 mg daily) gave a cure rate of only 30%. Dual and triple therapies were also studied, with the better results obtained with rifaximin-clarithromycin and rifaximin-clarithromycin-esomeprazole combinations. However, the eradication rates (60-70%) obtained with these regimens were still below the standard set by the Maastricht Consensus guidelines. Although rifaximin-based eradication therapies are promising, new antimicrobial combinations (with and without proton pump inhibitors) need to be explored in well-designed clinical trials including a large cohort of H. pylori-infected patients. The remarkable safety of rifaximin will allow high-dose regimens of longer duration (e.g. 10 or 14 days) to be tested with confidence in the hope of achieving better eradication rates. A drawback of rifaximin could be its inability to reach sufficiently high concentrations in the gastric mucus layer under and within which H. pylori is commonly located and this would likely affect eradication rate. Taking these considerations into account, bioadhesive rifaximin formulations able to better and persistently cover gastric mucosa, or combination with mucolytic agents, such as pronase or acetylcysteine, need to be evaluated in order to better define the place of this antibiotic in our therapeutic armamentarium.

Anti-Infective Agents↗
PubMed2006

Microbial flora in NSAID-induced intestinal damage: a role for antibiotics?

Upper gastrointestinal (GI) complications are well-recognized adverse events associated with non-steroidal anti-inflammatory drug (NSAID) use. However, NSAID-induced damage to the distal GI tract is also common and more frequent than previously recognized. These untoward effects include increased mucosal permeability, mucosal inflammation, anemia and occult blood loss, malabsorption, protein loss, ileal dysfunction, diarrhea, mucosal ulceration, strictures due to diaphragm disease as well as active bleeding and perforation. Studies with selective COX-2 inhibitors have shown that, in the short term, these agents do not increase mucosal permeability and display a reduced by 50% incidence of serious lower GI side effects compared to traditional NSAIDs. However, the long-term use of this therapeutic strategy is limited by the increased risk of serious cardiovascular events, especially in patients with multiple risk factors. Several studies have suggested that intraluminal bacteria play a significant role in the pathogenesis of small-bowel damage induced by NSAIDs and that enterobacterial translocation into the mucosa represents the first step that sets in motion a series of events leading to gross lesion formation. Experimental and clinical investigations indicate that in the short term, antibacterial agents either reduce or abolish NSAID enteropathy. However, potential adverse effects of systemic antimicrobials and the possible occurrence of drug resistance have so far precluded this interesting approach. The availability of poorly absorbed and effective antibiotics, like rifaximin, may represent an attractive alternative to prevent or limit NSAID-associated intestinal damage.

Anti-Infective Agents↗
PubMed2006

'Rescue' therapies for the management of Helicobacter pylori infection.

Helicobacter pylori infection is the main cause of gastritis, gastroduodenal ulcer and gastric cancer and should be considered as a major public health issue. According to several international guidelines, first-line therapy for treating H. pylori infection consists of proton pump inhibitor (PPI) or ranitidine bismuth citrate (RBC) with any two antibiotics of amoxicillin, clarithromycin or metronidazole given for 7-14 days. However, even with the recommended treatment regimens, approximately 20% of patients will fail to obtain H. pylori eradication. The proportion of patients with first-line H. pylori therapy failure may be higher in clinical practice and it may increase thanks to diffusion of H. pylori treatment. The recommended second-line therapy is the quadruple regimen composed by tetracycline, metronidazole, bismuth salts and a PPI. However, the efficacy of this regimen is limited by poor patient's compliance due to its side effects, number of tablets per day, and long duration. Moreover, bismuth and metronidazole are not available in all countries. Alternatively, a longer-lasting (i.e. 10-14 days) PPI or RBC triple therapy with two antibiotics has generally been used. In an empirical strategy, the choice of second line depends on the treatment initially used. If a clarithromycin-based regimen was administered in first line, a quadruple regimen or PPI (or RBC) triple therapy with metronidazole and amoxicillin (or tetracycline) should be suggested as a second line. In case of second-line treatment failure, the patient should be evaluated by a case-by-case approach. A susceptibility-guided strategy, if available, is recommended in order to choose the best third-line treatment. Culture can reveal the presence of H. pylori-sensitive strains to clarithromycin (the best effective) or other antimicrobials (such as amoxicillin, metronidazole and tetracycline). Conversely, in an empirical strategy, a third-line not yet used therapy, can reach a high success rate. PPI or RBC, amoxicillin and a new antimicrobial (e.g. rifabutin, levofloxacin or furazolidone) could be used. Several studies have obtained relatively good results with triple therapy combining PPI, rifabutin, and amoxicillin, although a reversible myelotoxicity as leukopenia and thrombocytopenia has been described. Preliminary good results were also achieved with triples PPI regimens combining levofloxacin and amoxicillin without important adverse effects. Furazolidone has also shown efficacy for H. pylori eradication, although untoward reactions could limit its use, especially when high doses are employed. Finally, in more than one H. pylori treatment failure, non-antimicrobial add-on medications (such as lactoferrin, probiotics and others) could be used with the aim either to improve the eradication rate or to minimize side effects.

Anti-Bacterial Agents↗
PubMed2006

Acid suppression therapy: where do we go from here?

The dramatic success of pharmacological acid suppression in healing peptic ulcers and managing patients with gastroesophageal reflux disease (GERD) has been reflected in the virtual abolition of elective surgery for ulcer disease, a reduction in nonsteroidal anti-inflammatory drug (NSAID)-associated gastropathy and the decision by most patients with reflux symptoms to continue medical therapy rather than undergo surgical intervention. However, a number of challenges remain in the management of acid-related disorders. These include management of patients with gastroesophageal symptoms who do not respond adequately to proton pump inhibitor (PPI) therapy, treatment of patients with nonvariceal upper gastrointestinal bleeding, prevention of stress-related mucosal bleeding, optimal treatment and prevention of NSAID-related gastrointestinal injury, and optimal combination of antisecretory and antibiotic therapy for the eradication of Helicobacter pylori infection. A number of new drugs are currently being investigated to provide a significant advance on current treatments. Some of them (namely potassium-competitive acid blockers (P-CABs) and CCK2-receptor antagonists) have already reached clinical testing while some others (like the antigastrin vaccine, H3-receptor ligands or gastrin-releasing peptide receptor antagonists) are still in preclinical development and need the proof of concept in human beings. Of the current approaches to reduce acid secretion, P-CABs and CCK2-receptor antagonists hold the greatest promise, with several compounds already in clinical trials. Although the quick onset of action of P-CABs (i.e. a full effect from the first dose) is appealing, the results of phase II studies with one such agent (namely AZD0865) did not show any advantages over esomeprazole. Thanks to their limited efficacy and the development of tolerance it is unlikely that CCK2 antagonists will be used alone as antisecretory compounds but, rather, their combination with PPIs will be attempted with the aim of reducing the long-term consequences of hypergastrinemia. While H2-receptor antagonists (especially soluble or over-the-counter formulations) will become the 'antacids of the third millennium' and will be particularly useful for on-demand symptom relief, clinicians will continue to rely on PPIs to control acid secretion in GERD and other acid-related diseases. In this connection, several new PPI formulations have been developed and two novel drugs (namely ilaprazole and tenatoprazole) are being studied in humans. The recently introduced immediate-release (IR) omeprazole formulation (currently available only in the USA) quickly increases intragastric pH and, given at bedtime, seems to achieve a better control of nocturnal acidity. IR formulations of other PPIs (including the investigational ones) will probably be available in the future and will enlarge our therapeutic armamentarium. Amongst the novel PPIs, tenatoprazole appears to be a true advance in the acid suppression therapy. Its long half-life (the longest among the available compounds) and longer duration of antisecretory action, with no difference between day and night, will allow the drug to go beyond the intrinsic limitations of currently available PPIs. Thanks to its favorable pharmacokinetics, the sodium salt of S-tenatoprazole is being developed and the preliminary results indicate that this drug has the potential to address unmet clinical needs. Although some decades have elapsed since the introduction of effective and safe antisecretory drugs in clinical practice and their use has stood the test of time, the ongoing research will further provide the clinician with more effective means of controlling acid secretion.

Anti-Ulcer Agents↗
PubMed2005

Myths and misconceptions about chronic constipation.

There are many strongly held beliefs about constipation that are not evidence based. The purpose of this review is to address these beliefs concerning various aspects of constipation. There is no evidence to support the theory that diseases may arise via "autointoxication," whereby poisonous substances from stools within the colon are absorbed. Dolichocolon, defined as an elongated colon, should not be seen as a cause of constipation. The role of sex hormones altering gut function during the menstrual cycle appears to be minimal. During pregnancy they may play a role in slowing gut transit. Hypothyroidism can cause constipation, but among patients presenting with constipation, hypothyroidism is rare. A diet poor in fiber should not be assumed to be the cause of chronic constipation. Some patients may be helped by a fiber-rich diet but many patients with more severe constipation get worse symptoms when increasing dietary fiber intake. There is no evidence that constipation can successfully be treated by increasing fluid intake unless there is evidence of dehydration. In the elderly constipation may correlate with decreased physical activity, but many cofactors are likely to play a role. Intervention programs to increase physical activity as part of a broad rehabilitation program may help. It is unlikely that stimulant laxatives at recommended doses are harmful to the colon. A proportion of patients with chronic constipation is dependent of laxatives to achieve satisfactory bowel function, but this is not the result of prior laxative intake. Tolerance to stimulant laxatives is uncommon. There is no indication for the occurrence of "rebound constipation" after stopping laxative intake. While laxatives may be misused, there is no potential for addiction.

Cathartics↗
PubMed2005

Rifaximin, a poorly absorbed antibiotic: pharmacology and clinical potential.

Rifaximin (4-deoxy-4'-methylpyrido[1',2'-1,2]imidazo- [5,4-c]-rifamycin SV) is a synthetic antibiotic designed to modify the parent compound, rifamycin, in order to achieve low gastrointestinal (GI) absorption while retaining good antibacterial activity. Both experimental and clinical pharmacology clearly show that this compound is a nonsystemic antibiotic with a broad spectrum of antibacterial action covering Gram-positive and Gram-negative organisms, both aerobes and anaerobes. Being virtually nonabsorbed, its bioavailability within the GI tract is rather high with intraluminal and fecal drug concentrations that largely exceed the minimal inhibitory concentration values observed in vitro against a wide range of pathogenic organisms. The GI tract represents, therefore, the primary therapeutic target and GI infections the main indication. The appreciation of the pathogenic role of gut bacteria in several organic and functional GI diseases has increasingly broadened its clinical use, which is now extended to hepatic encephalopathy, small intestine bacterial overgrowth, inflammatory bowel disease and colonic diverticular disease. Potential indications include the irritable bowel syndrome and chronic constipation, Clostridium difficile infection and bowel preparation before colorectal surgery. Because of its antibacterial activity against the microorganism and the lack of strains with primary resistance, some preliminary studies have explored the rifaximin potential for Helicobacter pylori eradication. Oral administration of this drug, by getting rid of enteric bacteria, could also be employed to achieve selective bowel decontamination in acute pancreatitis, liver cirrhosis (thus preventing spontaneous bacterial peritonitis) and nonsteroidal anti-inflammatory drug (NSAID) use (lessening in that way NSAID enteropathy). This antibiotic has, therefore, little value outside the enteric area and this will minimize both antimicrobial resistance and systemic adverse events. Indeed, the drug proved to be safe in all patient populations, including young children. Although rifaximin has stood the test of time, it still attracts the attention of both basic scientists and clinicians. As a matter of fact, with the advancement of the knowledge on microbial-gut interactions in health and disease novel indications and new drug regimens are being explored. Besides widening the clinical use, the research on rifaximin is also focused on the synthesis of new derivatives and on the development of original formulations designed to expand the spectrum of its clinical use.

Animals↗
PubMed2005

Rifaximin, a peculiar rifamycin derivative: established and potential clinical use outside the gastrointestinal tract.

Rifaximin is a poorly absorbed semisynthetic rifamycin derivative with a broad spectrum of antibacterial activity including Gram-positive and Gram-negative bacteria, both aerobes and anaerobes. Although originally developed for the treatment of infectious diarrhea, the appreciation of the pathogenic role of gut bacteria in several organic and functional gastrointestinal diseases has increasingly broadened its clinical use. The availability of a topical formulation (a cream containing 5% of the drug) and the lack of transcutaneous absorption pointed out in both animal and human studies has allowed its topical use in skin infections. Furthermore, since the spectrum of antibacterial action of rifaximin includes many organisms (e.g. Bacteroides bivius-disiens, Gardnerella vaginalis, Haemophilus ducreyi) causing genital infections, including Trichomonas vaginalis and Chlamydia trachomatis, its local application in the treatment of bacterial vaginosis (BV) has been attempted. Finally, since periodontal disease, caused by plaque (an aggregate of various bacteria), can be considered a 'local' infection, intrapocket rifaximin was tried in the treatment of periodontal infections. While the efficacy in pyogenic infections of the skin has been confirmed by several investigations, which showed an improvement of both subjective and objective parameters significantly better than that of the reference drug (i.e. chlortetracycline or oxytetracycline), the usefulness of rifaximin in BV and periodontal disease needs to be further studied in well-designed clinical trials.

Administration, Topical↗
PubMed2002

Dysphagia and clinical outcome after laparoscopic Nissen or Rossetti fundoplication: sequential prospective study.

Laparoscopic fundoplication represents the most widely used operation in the surgical treatment of gastroesophageal reflux disease (GERD). Besides being operator-dependent, the clinical outcome (efficacy and side-effects) seems also to be dependent on the specific surgical technique. In this prospective trial we compared the results of two groups of patients who were submitted sequentially to the Rossetti or Nissen fundoplication procedure. Dysphagia, other side effects, and clinical outcome were evaluated early after surgery and at 6 and 12 months after the operation. Although both procedures were clinically effective, there was a significant trend toward less postoperative dysphagia in the Nissen group. In these patients the incidence of early dysphagia was significantly lower than that observed in those submitted to the Rossetti fundoplication. In addition, Nissen patients experienced a significantly smaller number of days with dysphagia. One year after surgery, however, the two procedures proved equally successful without any significant difference in dysphagia incidence. Complete fundic mobilization should therefore be advised to reduce the incidence of early troublesome dysphagia.

Adolescent↗
PubMed2002

Early esophageal transit study after laparoscopic fundoplication: how useful is it?

BACKGROUND: Early complications of laparoscopic fundoplication, if immediately recognized, may be promptly treated laparoscopically with minimal morbidity. A suggested strategy for identification is a routine postoperative esophageal transit study. OBJECTIVE: To investigate the role of early postoperative esophagogram with Gastrografin in predicting major complications, failures, or severe dysphagia. DESIGN: Esophagograms performed in 92 patients, 24 hours after laparoscopic fundoplication, were correlated to major complications. Esophageal transit time was scored and correlated with dysphagia. RESULTS: Esophagogram detected two of three observed complications: acute paraesophageal hernia and intrathoracic migration, but not a fundic perforation. Only a severe transit impairment predicted a disabling dysphagia (specificity 82%, sensitivity 70%). CONCLUSIONS: Postoperative swallow is an appropriate investigation to diagnose anatomical abnormalities but may be deceptive for perforations. Severe transit delay may predict the risk of severe dysphagia. Although useful, postoperative routine transit studies would probably not change the therapeutic strategies in most patients.

Adult↗