Azithromycin is one of the newer orally administered macrolide antibiotics. Like clarithromycin, it too is acid stable. Azithromycin is well absorbed from the gastrointestinal tract and extensively distributed in tissues and reaches concentrations much greater than the MICs of common infectious pathogens.
The elimination half-life of azithromycin increases with time after the dose, and with each subsequent dose the elimination half-life increases. Ranitidine bismuth citrate RBC is a bismuth compound with histamine 2 -receptor—antagonist H 2 RA activity formed by the reaction of ranitidine with bismuth citrate and is precipitated as an amorphous compound. The RBC is freely soluble in water, whereas an equimolar admixture of ranitidine and bismuth citrate forms an almost insoluble suspension.
The RBC has antipepsin activity and enhanced antibacterial activity against H pylori that is not observed with the admixture of ranitidine and bismuth citrate. It is hypothesized that the greater solubility of RBC is what confers these added properties. When given alone, RBC has been shown to suppress H pylori.
The eradication rate of CBS and amoxicillin is dependent on both the total daily dose of amoxicillin and how frequently it is given. The eradication rates of CBS plus metronidazole have been variable with no consistent trend to suggest that more frequent or larger doses of metronidazole are required to improve eradication efficacy. Because of its variable results, as well as low rate of eradication, bismuth plus a single antibiotic is not considered adequate therapy for eradication.
Axon 31 reviewed several studies examining the eradication of H pylori using either omeprazole or lansoprazole with amoxicillin and found the results to be variable. However, these results have not been replicated in similar trials. Omeprazole pretreatment prior to the addition of amoxicillin has been demonstrated to reduce the efficacy of this combination significantly. Recently, the Food and Drug Administration has approved the marketing of clarithromycin and omeprazole for concurrent use in the treatment of duodenal ulcers associated with H pylori.
Chiba 41 demonstrated that reducing the dose of clarithromycin to mg twice a day in this regimen lowers the eradication rate Comparable results have been described with lansoprazole and clarithromycin. An eradication rate of In the US studies mentioned above, 3.
Both omeprazole and lansoprazole directly inhibit the growth of H pylori in vitro; therefore, using larger doses may possibly result in better eradication rates. This combination was recently approved by the Food and Drug Administration. As mentioned earlier, the combination of RBC with clarithromycin has been shown to be effective in eradicating H pylori infection.
These findings are consistent with previous studies 47 , 48 using similar doses and duration of treatment. The number of patients that left the study because of adverse reactions was similar between the treatment and placebo groups.
The early regimens used to eradicate H pylori used bismuth as the cornerstone of triple therapy. The most effective treatments consisted of bismuth plus 2 antibiotics—usually metronidazole and tetracycline or metronidazole and amoxicillin. Recently, Tefera et al 49 conducted a study using a triple therapy consisting of bismuth subcitrate mg 4 times a day , oxytetracycline mg 4 times a day , and metronidazole mg 3 times a day for 10 days. This implies that the efficacy of this regimen is highly dependent on metronidazole.
Another recent trial 50 demonstrated a similar eradication rate with a comparable regimen of bismuth, metronidazole, and tetracycline. Fifty-five infected patients received a day course of tetracycline mg , metronidazole mg , and CBS mg , 4 times a day. This regimen yielded a Of the 55 patients, 8 had H pylori isolates that were metronidazole resistant.
Seven of these 8 patients were tested for treatment efficacy, and all but 1 had cleared their infection using this triple antibiotic regimen. The implication is that this regimen is still quite effective for patients with metronidazole-resistant strains of H pylori , and this has been shown to be the case in several other trials. Treatment was for only a week. The most common adverse effects reported were nausea, dizziness, malaise, metallic taste, and anorexia. Six of the 55 patients enrolled could not complete the study because of the adverse effects of this combination.
Therefore, despite an acceptable rate of eradication, the higher doses of tetracycline and metronidazole in this regimen make it difficult to tolerate. Because of metronidazole-resistant strains of H pylori , investigators have substituted either clarithromycin or azithromycin for metronidazole in the standard bismuth-based triple therapies in an effort to overcome this problem.
Al-Assi et al 53 studied the combination of clarithromycin mg 3 times a day , tetracycline mg 4 times a day , and BSS 2 tablets [ mg per tablet] 4 times a day in 30 infected patients.
The combination was administered for 14 days. This combination is very effective against H pylori and may be an alternative treatment in those patients who are infected with metronidazole-resistant isolates. As mentioned, azithromycin is a new macrolide antibiotic that is very active against H pylori and achieves excellent tissue penetration with a long half-life. In one study, 54 30 patients with H pylori infection were treated with 1 of 2 regimens: 2 tablets of BSS each tablet contained mg of bismuth 4 times a day, tetracycline hydrochloride mg 4 times a day , and either azithromycin mg twice a day in one group [18 patients] or mg 3 times a day in the other [12 patients] for 2 weeks.
Despite a comparable eradication rate to other effective bismuth-based triple therapies, this triple therapy is limited because its efficacy relies on high doses of azithromycin, which produce much too high a rate of adverse effects to make this regimen practical.
Another trial 55 studied the combination of azithromycin, metronidazole, and bismuth. Fifty-six patients infected with H pylori received bismuth subcitrate mg 4 times a day for 14 days along with azithromycin mg daily for the first 3 days and metronidazole mg 4 times a day for the first 7 days. The eradication rate for this regimen was Only 3 patients in this group experienced an adverse event; however, all were able to complete treatment.
Although the adverse-effect profile improved by decreasing the dose and frequency of azithromycin administration, the eradication rate was significantly lowered, making this regimen impractical. Most studies regarding bismuth-based triple therapy have been conducted using CBS, but more recent trials suggest that BSS can achieve similar eradication rates in the same combinations. To date, the bismuth-based triple therapies are the most effective and least costly treatments for the eradication of H pylori , because they have high cure rates even in those patients infected with metronidazole-resistant strains.
Unfortunately, compliance is poor with these regimens because of the large number of tablets and frequent adverse effects.
Still, the search for therapies that are more effective than bismuth-based regimens is ongoing. In an attempt to find more tolerable triple drug regimens, proton pump inhibitors have been studied in combination with 2 other antibiotics.
The most studied has been omeprazole in combination with either metronidazole and amoxicillin or metronidazole and clarithromycin.
More recently, in a randomized trial, 60 31 patients were treated with a 1-week course of this omeprazole-antibiotic combination. This implies that perhaps it is necessary to treat patients with this regimen longer to achieve a higher eradication rate. A smaller study 61 evaluated the efficacy of triple therapy using metronidazole, omeprazole, and clarithromycin. Thirty-three patients with documented H pylori infection received omeprazole 20 mg twice a day , clarithromycin mg twice a day , and metronidazole mg twice a day for 2 weeks.
A similar eradication rate This regimen has also been shown to retain its efficacy when given for only a week. Additionally, the efficacy of this therapy is also dependent on the length of time that it is given.
In a small randomized trial, 63 patients received omeprazole 20 mg twice daily , clarithromycin mg twice daily , and amoxicillin 1 g twice daily for 7, 10, or 14 days. Lansoprazole, another proton pump inhibitor, has been shown to be just as effective as omeprazole in triple antibiotic therapy. In a multicenter trial 64 conducted in the United Kingdom and Ireland, patients with either duodenal ulcer or gastritis and H pylori infection were randomized to 1 of 4 1-week regimens: lansoprazole 30 mg twice a day plus clarithromycin mg twice a day with either amoxicillin 1 g or metronidazole mg twice daily or amoxicillin 1 g plus metronidazole mg twice a day with either lansoprazole 30 mg or omeprazole 20 mg twice a day.
The combination of lansoprazole, amoxicillin, and clarithromycin and lansoprazole, clarithromycin, and metronidazole had eradication rates of The eradication rates of the lansoprazole, amoxicillin, and metronidazole and omeprazole, amoxicillin, and metronidazole therapies were Histamine 2 -receptor antagonists H 2 RAs have been used in combination with 2 antibiotics for the eradication of H pylori with good success.
The addition of ranitidine enhances the eradication rate of dual antibiotic therapy. In a randomized, double-blind, multicenter trial, 67 patients were randomized to either metronidazole mg 3 times a day and tetracycline mg 4 times a day with either ranitidine mg 4 times a day or placebo.
Eradication in the group receiving ranitidine was significantly enhanced with an eradication rate of A recent meta-analysis by Holtmann et al 69 suggests that eradication of H pylori with H 2 RAs in combination with antibiotics is similar to proton pump inhibitor combinations. Thus, omeprazole has an advantage over ranitidine with respect to antibiotic resistance.
This may be omeprazole's intrinsic antibacterial activity against H pylori , which ranitidine and other H 2 RAs do not possess. Quadruple antibiotic therapies have consisted of traditional bismuth-based triple therapy with the addition of an antisecretory agent, either an H 2 RA or a proton pump inhibitor, to achieve close to complete eradication.
These regimens have consistently achieved high eradication rates. In a randomized placebo-controlled trial, 71 consecutive patients with peptic ulcer disease and biopsy-proven H pylori infection were randomized to 7 days of triple therapy with or without omeprazole 20 mg twice a day or placebo. Triple antibiotic therapy consisted of CBS mg 4 times a day , tetracycline hydrochloride mg 4 times a day , and metronidazole mg 3 times a day.
Addition of omeprazole to this traditional triple therapy enhanced its efficacy. In another trial, 72 addition of either omeprazole or famotidine to triple antibiotic therapy was studied to see if the efficacy of triple antibiotic therapy could be improved. This prospective, randomized study enrolled patients with symptoms of dyspepsia and confirmed H pylori infection.
Patients received a day course of CBS chewable tablets mg 4 times a day, tetracycline mg 4 times a day , and metronidazole mg 4 times a day in addition to either omeprazole 20 mg twice daily or famotidine 40 mg at bedtime. One-hundred twenty two of the Again, addition of a proton pump inhibitor resulted in enhanced eradication efficacy despite a greater prevalence of metronidazole-resistant isolates.
If you are taking a PPI , your doctor will ask you to stop taking PPI medications for one or two weeks before the test. This test is available for adults and children older than 3.
A laboratory test called a stool polymerase chain reaction PCR test can detect H. This test is more expensive and may not be available at all medical centers. This test is available for adults and children. Breath test. During a breath test, you swallow a pill, liquid or pudding that contains tagged carbon molecules. If you have an H. Your body absorbs the carbon and expels it when you exhale.
You exhale into a bag, and your doctor uses a special device to detect the carbon molecules. As with stool tests, PPIs , bismuth subsalicylate Pepto-Bismol and antibiotics can interfere with the accuracy of this test. If you are taking a PPI , your doctor will ask you to stop taking the PPI medications for one or two weeks before the test. Scope test. You'll be sedated for this test, known as an upper endoscopy exam.
During the exam, your doctor threads a long flexible tube equipped with a tiny camera endoscope down your throat and esophagus and into your stomach and duodenum. This instrument allows your doctor to view any irregularities in your upper digestive tract and remove tissue samples biopsy. These samples are analyzed for H.
This test is done to investigate symptoms that may be caused by other conditions such as gastric ulcer or gastritis that may be due to H. The test may be repeated after treatment depending on what is found at the first endoscopy or if symptoms persist after H. At this second exam, biopsies can be performed to make sure H. This test isn't always recommended solely to diagnose an H. But it may be used to perform detailed testing for doctors to determine exactly which antibiotic to prescribe to treat H.
Your doctor also will prescribe or recommend an acid-suppressing drug, to help your stomach lining heal. Your doctor may recommend that you undergo testing for H. Metronidazole, mg twice daily. Tetracycline, mg twice daily. Amoxicillin, 1 g twice daily. Quadruple therapy. Metronidazole, mg four times daily. Tetracycline, mg four times daily. H 2 RA for 28 days. PPI for 14 days. Food and Drug Administration should not be used because of their lower eradication rates and potential for antimicrobial resistance.
Montvale, N. Cost to patient will be higher depending on filling fees. Amoxicillin, a semi-synthetic penicillin, is an effective antibiotic for H. The frequency of amoxicillin-resistant H. The drug rapidly accumulates in antral mucosa via systemic circulation.
Its antimicrobial activity against H. Erythromycin and azithromycin are much less effective macrolides in vivo and should not be used in H. The H. Increasing the gastric pH with the use of a histamine H 2 -receptor antagonist H 2 RA or a PPI has been shown to improve the effectiveness of antibiotic therapy.
In addition, PPIs have demonstrated antimicrobial activity against H. Bismuth salts have no substantial acid-neutralizing capacity but inhibit pepsin, increase secretion of mucus, and form a barrier to the diffusion of acid in the ulcer crater. They also cause detachment of H. Side effects include darkening of the oral cavity and stool.
Ranitidine bismuth citrate is a combination salt with intrinsic antisecretory and antimicrobial activity that is effective in combination with antibiotics in the eradication of H. It is not effective as monotherapy. Because patient adherence to therapy is critical, simpler regimens with twice-daily dosing may be more successful in eradicating the H.
Based on efficacy, PPI triple therapy or bismuth quadruple therapy for 14 days are recommended in the United States as first-line treatments for patients with H. PPI quadruple therapy or a regimen including furazolidone may serve as second-line treatment for eradication of initial failures and in cases of metronidazole resistance. In addition to H. The use of NSAIDs and tobacco increase the risk of peptic ulcer disease, particularly of the stomach. Patient education about the need for effective eradication therapy and the necessity of completing the initial drug regimen is critical.
A follow-up plan must be emphasized because further diagnostic testing may be needed to ensure eradication of the H. Patients with a history of ulcer complications, gastric mucosa-associated lymphoid tissue MALT , or early gastric cancer should undergo a routine post-treatment urea breath test or endoscopy to ensure successful eradication.
These patients will usually be followed in collaboration with a gastroenterologist. Routine, noninvasive follow-up testing also can be considered in patients who have persistent symptoms following eradication therapy. In these patients, the stool antigen test, performed four weeks following therapy, is a convenient alternative.
Because of the risk of ulcer recurrence and the potential for malignant transformation caused by H. Serology is not practical as a test for cure because it can take more than one year to revert to negative; however, a negative result is predictive of successful eradication.
To date, good evidence does not exist to support routine laboratory testing for cure in patients whose symptoms respond to eradication therapy for uncomplicated ulcer disease or undifferentiated dyspepsia.
Patients with persistent H. Data from one study 38 in which patients were treated with quadruple therapy that included lansoprazole 30 mg twice daily , tetracycline mg four times daily , metronidazole mg three times daily and bismuth sub-citrate mg four times daily for one week resulted in eradication in 20 of 21 patients who had not responded to triple therapy.
When treatment fails a second time, patients should be referred to a gastroenterologist. Already a member or subscriber? Log in. Interested in AAFP membership? Learn more. Bower obtained his medical degree from the University of Wisconsin Medical School, Madison, and completed a residency in family practice at the Grand Rapids Mich. Family Practice Residency. The authors indicate that they do not have any conflict of interest.
Sources of funding: none reported. Address correspondence to Linda N. Meurer, M. Box , Milwaukee, WI e-mail: lmeurer mcw. Reprints are not available from the authors. Symptoms, gastritis, and Helicobacter pylori in patients referred for endoscopy. Gastrointest Endosc. Prevalence of Helicobacter pylori infection and histologic gastritis in asymptomatic persons. N Engl J Med. Infection with Helicobacter pylori. Epidemiology of Helicobacterpylori in an asymptomatic population in the United States.
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Duodenalulcer treated with Helicobacter pylori eradication: seven-year follow-up Lancet. Has the impact of Helicobacter pylori therapy on ulcer recurrence in the Unites States been overstated? A meta-analysis of rigorously designed trials.
Effect of treatment of Helicobacter pylori infection on the long-term recurrence of gastric or duodenal ulcer. Ann Intern Med. Therapy for Helicobacter pylori in patients with nonulcer dyspepsia. A meta-analysis of randomized, controlled trials.
Eradication of Helicobacter pylori for non-ulcer dyspepsia. Cochrane Database Syst Rev. Helicobacter pylori in peptic ulcer disease. Can J Gastroenterol. Evaluation of the dyspeptic patient: a cost-utility study. J Fam Pract.
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