The standard strategy for H. pylori infection in Japan consists of the triple PPI/AMPC/CAM therapy as the first line therapy and the triple PPI/AMPC/MNZ therapy as the second line therapy. 2 or 3% of patients cannot achieve eradication of H. pylori with the above two regimens. Most of them are infected with CAM resistant strains of H. pylori and have the rapid metabolizer genotype of CYP2C19. There are two major third line therapies. One is the dual therapy with high doses (qid dosing) of PPI and AMPC. The other is fluoroquinolone-based therapy. Especially, sitafloxacin, one of the fluoroquinolones, has the lower MIC for H. pylori in comparison with other fluoroquinolones, such as LVFX. Both therapies are expected to achieve the high eradication rate as the 3rd line therapy.

BACKGROUND. Persistent infection with Helicobacter pylori is associated with the recurrence of duodenal ulcer. Whether the efficacy of bismuth therapy in reducing the rate of recurrence of duodenal ulcer is due to its antimicrobial effects on H. pylori or to a direct protective action on the mucosa is still a matter of debate. METHODS. To study the effect of the eradication of H. pylori on the recurrence of duodenal ulcer, we treated 104 patients with H. pylori infection and recurrent duodenal ulcer with either amoxicillin (750 mg three times daily) plus metronidazole (500 mg three times daily) or identical-appearing placebos, given orally for 12 days. All patients also received ranitidine (300 mg each night) for 6 or 10 weeks. Endoscopy was performed before treatment and periodically during follow-up for up to 12 months after healing. RESULTS. Among the 52 patients given antibiotics, H. pylori was eradicated in 46, as compared with 1 of the 52 given placebo (89 percent vs. 2 percent, P < 0.001). After six weeks, the ulcers were healed in 48 patients given antibiotics and 39 given placebo (92 percent vs. 75 percent, P = 0.011). Side effects, mainly diarrhea, occurred in 15 percent of the patients given antibiotics. Among the patients followed up for 12 months, duodenal ulcers recurred in 4 of 50 patients given antibiotics and 42 of 49 given placebo (8 percent vs. 86 percent, P < 0.001). Ulcers recurred in 1 of 46 patients in whom H. pylori had been eradicated, as compared with 45 of 53 in whom H. pylori persisted (2 percent vs. 85 percent, P < 0.001). CONCLUSIONS. In patients with recurrent duodenal ulcer, eradication of H. pylori by a regimen that does not have any direct action on the mucosa is followed by a marked reduction in the rate of recurrence, suggesting a causal role for H. pylori in recurrent duodenal ulcer.

The potential use of an adjunctive therapy of metronidazole plus amoxycillin for the subgingival elimination of Actinobacillus actinomycetemcomitans in periodontitis patients was investigated. 22 patients participated in this study, 11 with localized juvenile periodontitis (LJP) and 11 with rapidly progressive periodontitis (RPP). 14 patients had received periodontal treatment in the past. All patients were subgingivally infected with A. actinomycetemcomitans. After mechanical subgingival debridement in combination with the antibiotic treatment, elimination of A. actinomycetemcomitans was achieved in all patients but one. With this one exception, clinical improvements were observed in all patients, resulting in reduced pocket probing depths as well as in a significant reduction in bleeding on probing. Re-examination of 16 patients after 9-11 months revealed that A. actinomycetemcomitans was still undetectable and further clinical improvement was observed. It was concluded that the combination of metronidazole plus amoxycillin is a valuable adjunct to mechanical therapy in A. actinomycetemcomitans associated periodontal infections.

In randomized, double-blind trials of antibiotic therapy for acute otitis media that determined both clinical and bacteriologic outcomes, clinical success rates were (93%) 236 of 253 for patients with bacteriologic success,(62%) 25 of 40 for those with bacteriologic failure, and (80%) 124 of 155 for those with nonbacterial acute otitis media. These rates were used to calculate the effectiveness of three strategies for assessing drug efficacy:(1) tympanocentesis and culture before and during therapy (bacteriologic efficacy),(2) tympanocentesis before therapy and assessment of clinical efficacy in bacterial acute otitis media, and (3) no tympanocentesis and assessment of clinical efficacy in clinical (total) acute otitis media. For a drug with a bacteriologic efficacy of 100%, calculated clinical efficacy was 93% for bacterial acute otitis media and 89% for clinical acute otitis media. For a drug with bacteriologic efficacy of 27%, a rate consistent with no antibacterial therapy, efficacy was 71% for bacterial acute otitis media and 74% for clinical acute otitis media. We conclude that if efficacy is measured by symptomatic response, drugs with excellent antibacterial activity will appear less efficacious than they really are and drugs with poor antibacterial activity will appear more efficacious than they really are. The predominant phenomenon is that drugs with poor antibacterial activity will appear to be clinically effective in the treatment of acute otitis media.

BACKGROUND/AIMS: Anti-Helicobacter pylori treatment with combinations of omeprazole and amoxicillin is a promising treatment option. The aim of this study was to investigate whether a daily omeprazole dose of 120 mg combined with amoxicillin would cure H. pylori infection at a rate comparable with that achieved with "triple therapy." METHODS: In a double-blind, randomized, controlled, and multicenter trial in Germany, 270 patients with an H. pylori-associated duodenal ulcer were treated with 40 mg omeprazole three times a day and 750 mg amoxicillin three times a day for the first 14 days (n = 139) followed by 20 mg omeprazole once daily until day 42 or with omeprazole plus 750 mg amoxicillin placebo three times a day for the same time period (n = 131). RESULTS: Cure rates of H. pylori infection were 91% in the omeprazole plus amoxicillin group, 0% in the omeprazole plus placebo group, and 89% and 0%, respectively, performing an intention-to-treat analysis. Cure of H. pylori infection in patients pretreated with omeprazole was only 58% compared with 95% in patients who were not. The cumulative 12-month relapse rates were 11.3% and 44% in the treatment groups and 1.6% in H. pylori-negative and 49% in H. pylori-positive patients. CONCLUSIONS: The combination of 120 mg omeprazole daily and 2.25 g amoxicillin daily with its H. pylori cure rate of around 90% is one of the best tolerated and most effective treatment regimens.

We report on the microbiological and clinical effects of mechanical debridement in combination with metronidazole plus amoxicillin therapy in 118 patients with Actinobacillus actinomycetemcomitans-associated periodontitis. Patients were categorized into 3 groups: 28 had localized periodontitis; 50 had generalized periodontitis, and 40 had refractory periodontitis. After initial treatment and metronidazole plus amoxicillin therapy 114 of 118 (96.6%) patients had no detectable A. actinomycetemcomitans. Significant reduction in pocket probing depth and gain of clinical attachment were achieved in almost all patients. Four patients were still positive for A. actinomycetemcomitans after therapy. Metronidazole resistance (MIC greater than 25 micrograms/ml) was observed in 2 of 4 strains from these patients. Patients still positive for A. actinomycetemcomitans or Porphyromonas gingivalis showed a significant higher bleeding tendency after therapy. It was concluded that mechanical periodontal treatment in combination with the metronidazole plus amoxicillin therapy is effective for subgingival suppression of A. actinomycetemcomitans in patients with severe periodontitis.

32 children (mean age 12 years, range 6-18) with non-specific abdominal pain and Campylobacter pylori positive gastritis received a six week course of daily oral amoxycillin (50 mg/kg) and tinidazole (20 mg/kg). Before treatment and one month after stopping treatment, endoscopic biopsy samples were taken from the antral mucosa and serum C pylori IgG antibody, pepsinogen I, and gastrin levels were measured in fasting blood samples. One month after treatment 30 children (94%) were cleared of C pylori and gastritis had resolved in 27 (84%) and was improved in the remaining 5. Serum IgG, pepsinogen I, and gastrin levels were significantly decreased after treatment. Of 12 children assessed at six months, 9 remained free of C pylori. Increases or decreases in IgG level indicated clearance or recurrence, respectively, of C pylori.

BACKGROUND: Omeprazole plus amoxicillin may cure Helicobacter pylori infection. However, the published results vary rather widely, and the factors influencing the treatment success remain unclear. METHODS: Four hundred and twenty-three H. pylori-positive patients were treated with 1- or 2-week regimens comprising 40 mg or 80 mg omeprazole and amoxicillin in 11 prospective protocols. A complete set of data was available for 405 patients (ulcer disease, n = 383; dyspepsia, n = 22) and was submitted to uni- and multi-variate statistical analyses to elucidate the factors affecting the cure rates of the infection; 18 patients were lost to follow-up. RESULTS: The overall proportion of H. pylori cure was 76%. Insufficient compliance (p < 0.001), a short duration of treatment (p < 0.001), smoking (p = 0.003), and omeprazole pretreatment (p = 0.041) were the significant independent factors predicting treatment failure, whereas advanced age (p = 0.002), high scores of grade and of activity of gastritis (p = 0.035 and p = 0.019, respectively), and gastric ulcer disease (p = 0.058) were independent factors predicting treatment success. CONCLUSIONS: Several patient- and therapy-related factors diminish or increase the rate of H. pylori cure obtained by omeprazole/amoxicillin. These should be considered in future studies comparing different treatment regimens for curing H. pylori infection and also when designing treatment regimens applicable for routine clinical practice.

Treatment with amoxicillin and omeprazole resulted in encouraging Helicobacter pylori eradication rates in pilot studies that included medium term follow up. These results were evaluated in a prospective, randomised and controlled study. Forty patients with active duodenal ulcer disease and H pylori colonisation of the gastric mucosa were randomly assigned to receive either omeprazole (20 mg twice daily) and amoxicillin suspension (500 mg four times daily) for two weeks (group I) or bismuth subsalicylate (600 mg three times daily), metronidazole (400 mg three times daily), tetracycline (500 mg three times daily), and ranitidine (300 mg in the evening) for two weeks (group II). Study medication was followed in both groups by a four week treatment course with 300 mg ranitidine up to the final examination. One patient from each group was lost to follow up. H pylori was eradicated in 78.9% of group I and 84.2% of group II (p = 1.00). All ulcers in patients on omeprazole plus amoxicillin healed but in the triple treatment group four patients had residual peptic lesions after six weeks (ulcer healing rate: 78.9%, p = 0.11). Complete pain relief occurred after a median duration of 1 day in group I and of 6 days in group II (p = 0.03). There were no major complications in either group but minor side effects were more frequently recorded in patients on triple therapy (63.2% v 15.8%, p < 0.01). In conclusion, two weeks of treatment with omeprazole plus amoxicillin is as good as triple therapy plus ranitidine in eradicating H pylori but seems better with regard to safety, pain relief, and ulcer healing. Thus, amoxicillin plus omeprazole should be recommended as the treatment of choice in eradicating H pylori in patients with duodenal ulcer disease.

Helicobacter pylori infection is mainly acquired in childhood, and studies on the epidemiology of this infection depend on the availability of a noninvasive diagnostic test for use in children. The aim of this study was to determine whether the carbon 13-labeled urea breath test (UBT) can be used in children by evaluating:(1) its sensitivity and specificity compared with either culture or both rapid urease test and histologic examination,(2) whether a test meal or a prolonged fast is required,(3) the usefulness after treatment for H. pylori. Eighty-eight children (mean age, 10.6 +/- 4.19 years) who were undergoing upper endoscopy were studied while fasting, not fasting, and after treatment. Children were given 50 mg of 13C-urea if they weighed less than 50 kg or 75 mg of 13C-urea if they weighed more than 50 kg with 50 mg of a glucose polymer solution in 7.5 ml of water. Breath samples were collected at baseline and at 15, 30, 45, and 60 minutes. In 63 fasting children the UBT was 100% sensitive and 97.6% specific at 30 minutes with a cutoff value of 3.5 delta 13CO2 per mil. Nonfasting tests in 23 children, performed between 1 and 2 hours after their usual meal, were 100% sensitive and 91.6% specific. In 13 children fed directly before the UBT, the sensitivity of the test was reduced to 50%. Thirty minutes was the optimal sampling time. There was a significant decrease in specificity when samples were obtained at 15 minutes, possibly caused by the interference of oral urease-producing organisms. The test was 100% sensitive and specific in 20 children after treatment for H. pylori infection. The UBT is a highly sensitive and specific test for the diagnosis of H. pylori infection in children. Neither a prolonged fast nor a test meal is required.

Helicobacter pylori is present in up to 87% of patients with nonulcer dyspepsia. This study assessed the effect of eradicating Helicobacter pylori infection on the symptoms of nonulcer dyspepsia at four weeks and one year after treatment. Dyspepsia was assessed on the frequency and severity of six symptoms [epigastric pain (night and day), nausea and vomiting, upper abdominal discomfort, and regurgitation] where each symptom was scored from 0 to 4. Helicobacter pylori status was assessed before treatment and four weeks after treatment with histology and microbiology, and at one year with a carbon-13 urea breath test. Eighty-three patients (23 males, 60 females; mean age 56.3 years; mean symptom duration 3.6 months) with nonulcer dyspepsia and Helicobacter pylori infection entered the study. Seventy-five were available at one year follow-up. Four weeks after treatment, the mean symptom score improved in those with eradication (6.95-2.3, P = 0.01, N = 41) or persistent infection (6.69-3.0, P = 0.015, N = 42). At one year, those with persistent Helicobacter pylori infection (N = 38, score 5.24) had a higher score than those remaining clear of infection (N = 24, score 1.4, P < 0.0001) and those with reinfection (N = 13, score 2.2, P < 0.0001). In addition, persistent Helicobacter pylori infection was associated with more additional treatments than those with eradication (34/38 versus 4/37, P < 0.001). These results suggest that Helicobacter pylori plays an important role in the symptoms of nonulcer dyspepsia.