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      An Alternative Salvage Regimen for Helicobacter pylori-Resistant Patients with Heart Failure

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          Helicobacter pylori infects over 50% of the worldwide population. For eradication, European, Canadian, and American guidelines recommend a regimen consisting of a proton pump inhibitor, clarithromycin, and metronidazole or amoxicillin dosed twice daily for at least 7 days. When this treatment strategy fails, a complex, multidosed bismuth-based quadruple regimen is recommended. Unfortunately, for patients with heart failure, this salvage regimen can be potentially hazardous due to the drug-drug interaction with tetracycline and digoxin, as well as the large salicylate content with bismuth subsalicylate. As H. pylori infection is so prevalent, providers will most likely encounter such a therapeutic dilemma. A safe, effective, and simplistic alternative is a 10-day fluoroquinolone-based regimen consisting of a proton pump inhibitor, levofloxacin and either clarithromycin or amoxicillin. Levofloxacin demonstrates excellent bioavailability, widespread tissue and fluid distribution, extended half-life, limited drug interaction profile, low incidence of side effects, and remarkable activity against H. pylori with minimal primary resistance. Compared to the 7-day quadruple regimen, a 10-day levofloxacin-based regimen demonstrated a greater eradication rate, better tolerability, and a lower rate of therapy discontinuation. We briefly provide a summary of the data regarding this levofloxacin-based regimen and two successful cases from our heart failure clinic.

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          Most cited references 14

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          Current concepts in the management of Helicobacter pylori infection--the Maastricht 2-2000 Consensus Report.

          Significant progress and new insights have been gained in the 4 years since the first Maastricht Consensus Report, necessitating an update of the original guidelines. To achieve this, the European Helicobacter Pylori Study Group organized a meeting of specialists and experts from around the world, representatives from National Gastroenterology Societies and general practitioners from Europe to establish updated guidelines on the current management of Helicobacter pylori infection. The meeting took place on 21-22 September 2000. A "test and treat" approach is recommended in adult patients under the age of 45 years (the age cut-off may vary locally) presenting in primary care with persistent dyspepsia, having excluded those with predominantly gastro-oesophageal reflux disease symptoms, non-steroidal anti-inflammatory drug users and those with alarm symptoms. Diagnosis of infection should be by urea breath test or stool antigen test. As in the previous guidelines, the eradication of H. pylori is strongly recommended in all patients with peptic ulcer, including those with complications, in those with low-grade gastric mucosa-associated lymphoid tissue lymphoma, in those with atrophic gastritis and following gastric cancer resection. It is also strongly recommended in patients who are first-degree relatives of gastric cancer patients and according to patients' wishes after full consultation. It is advised that H. pylori eradication is considered to be an appropriate option in infected patients with functional dyspepsia, as it leads to long-term symptom improvement in a subset of patients. There was consensus that the eradication of H. pylori is not associated with the development of gastro-oesophageal reflux disease in most cases, and does not exacerbate existing gastro-oesophageal reflux disease. It was agreed that the eradication of H. pylori prior to the use of non-steroidal anti-inflammatory drugs reduces the incidence of peptic ulcer, but does not enhance the healing of gastric or duodenal ulcer in patients receiving antisecretory therapy who continue to take non-steroidal anti-inflammatory drugs. Treatment should be thought of as a package which considers first- and second-line eradication therapies together. First-line therapy should be with triple therapy using a proton pump inhibitor or ranitidine bismuth citrate, combined with clarithromycin and amoxicillin or metronidazole. Second-line therapy should use quadruple therapy with a proton pump inhibitor, bismuth, metronidazole and tetracycline. Where bismuth is not available, second-line therapy should be with proton pump inhibitor-based triple therapy. If second-line quadruple therapy fails in primary care, patients should be referred to a specialist. Subsequent failures should be handled on a case-by-case basis by the specialist. In patients with uncomplicated duodenal ulcer, eradication therapy does not need to be followed by further antisecretory treatment. Successful eradication should always be confirmed by urea breath test or an endoscopy-based test if endoscopy is clinically indicated. Stool antigen test is the alternative if urea breath test is not available.
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            Helicobacter pylori and antimicrobial resistance: molecular mechanisms and clinical implications.

            Helicobacter pylori is an important human pathogen that colonises the stomach of about half of the world's population. The bacterium has now been accepted as the causative agent of several gastroduodenal disorders, ranging from chronic active gastritis and peptic ulcer disease to gastric cancer. The recognition of H pylori as a gastric pathogen has had a substantial effect on gastroenterological practice, since many untreatable gastroduodenal disorders with uncertain cause became curable infectious diseases. Treatment of H pylori infection results in ulcer healing and can reduce the risk of gastric cancer development. Although H pylori is susceptible to many antibiotics in vitro, only a few antibiotics can be used in vivo to cure the infection. The frequent indication for anti-H pylori therapy, together with the limited choice of antibiotics, has resulted in the development of antibiotic resistance in H pylori, which substantially impairs the treatment of H pylori-associated disorders. Antimicrobial resistance in H pylori is widespread, and although the prevalence of antimicrobial resistance shows regional variation per antibiotic, it can be as high as 95%. We focus on the treatment of H pylori infection and on the clinical relevance, mechanisms, and diagnosis of antimicrobial resistance.
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              Inactivation of digoxin by the gut flora: reversal by antibiotic therapy.

              In approximately 10 per cent of patients given digoxin, substantial conversion of the drug to cardioinactive, reduced metabolites (digoxin reduction products, or DRPs) occurs. The site and clinical importance of this conversion is unknown. In four normal volunteers taking digoxin daily for four weeks, urinary excretion of DRPs was greatest after a poorly absorbed tablet was ingested, and least after intravenous administration, Stool cultures from subjects known to make DRPs in vivo ("excretors") converted digoxin to DRPs; cultures from nonexcretors did not. Three excretors were given tablets for 22 to 29 days. A five-day course of erythromycin or tetracycline, administered after a base-line period of 10 to 17 days, markedly reduced or eliminated DRP excretion in urine and stool. Serum digoxin concentrations rose as much as twofold after antibiotics were given. We conclude that in some persons digoxin is inactivated by gastrointestinal bacteria. Changes in the enteric flora may markedly alter the state of digitalization.

                Author and article information

                S. Karger AG
                April 2008
                31 October 2007
                : 110
                : 2
                : 112-115
                aDepartment of Clinical Pharmacy, UCHSC, Schools of Pharmacy and Medicine and bDivision of Cardiology, UCHSC, School of Medicine, Denver, Colo., USA
                110489 Cardiology 2008;110:112–115
                © 2007 S. Karger AG, Basel

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                Page count
                Tables: 2, References: 18, Pages: 4
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