Proton pump inhibitor-based triple therapies are performed worldwide for Helicobacter pylori-associated diseases in childhood. As the first-line therapy, the Japanese Pediatric Guideline in H. pylori Infection has recommended a triple regimen with amoxicillin and clarithromycin, because the Japanese national health care insurance system has permitted only this regimen. However, the primary resistance to clarithromycin in Japan is demonstrated in around 30% of the strains, leaving an urgent issue for the physicians. A triple regimen with amoxicillin and metronidazole is acceptable as the second-line therapy. In children with chronic H. pylori gastritis, eradication should be considered if they have gastric atrophy or a family history of gastric cancer. In children, however, a 'test and treat' strategy to prevent gastric cancer is not recommended.

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.

To assess the cause of nonspecific vaginitis, we performed a prospective case-control study of vaginal flora and a randomized unblinded trial of different therapies. Haemophilus vaginalis was isolated from 17 to 18 women with signs of vaginitis but only one of 18 normal matched controls (P less than 0.002). The concentration of anaerobic bacteria in vaginal washings also was increased in patients. Clinical improvement and eradication of H. vaginalis occurred in one of seven patients given sulfonamide vaginal cream, two of 15 given oral doxycycline, nine of 27 given oral ampicillin, and 80 of 81 given oral metronidazole. On the seventh day of therapy signs of nonspecific vaginitis persisted in 31 of 31 with, and in two of 92 without, persistent H. vaginalis infection (P less than 0.001). These data suggest the causal role of H. vaginalis in nonspecific vaginitis, possibly in concert with vaginal anaerobes. The widespread use of sulfonamide creams is inappropriate. Metronidazole is effective, but its efficacy must be weighed against its possible toxicity.

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.

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.

Metronidazole is effective for the treatment of acute pouchitis after ileal pouch-anal anastomosis, but it has not been directly compared with other antibiotics. This randomized clinical trial was designed to compare the effectiveness and side effects of ciprofloxacin and metronidazole for treating acute pouchitis. Acute pouchitis was defined as a score of 7 or higher on the 18-point Pouchitis Disease Activity Index (PDAI) and symptom duration of 4 weeks or less. Sixteen patients were randomized to a 2-week course of ciprofloxacin 1,000 mg/d (n = 7) or metronidazole 20 mg/kg/d (n = 9). Clinical symptoms, endoscopic findings, and histologic features were assessed before and after therapy. Both ciprofloxacin and metronidazole produced a significant reduction in the total PDAI score as well as in the symptom, endoscopy, and histology subscores. Ciprofloxacin lowered the PDAI score from 10.1+/-2.3 to 3.3+/-1.7 (p = 0.0001), whereas metronidazole reduced the PDAI score from 9.7+/-2.3 to 5.8+/-1.7 (p = 0.0002). There was a significantly greater reduction in the ciprofloxacin group than in the metronidazole group in terms of the total PDAI (6.9+/-1.2 versus 3.8+/-1.7; p = 0.002), symptom score (2.4+/-0.9 versus 1.3+/-0.9; p = 0.03), and endoscopic score (3.6+/-1.3 versus 1.9+/-1.5; p = 0.03). None of patients in the ciprofloxacin group experienced adverse effects, whereas three patients in the metronidazole group (33%) developed vomiting, dysgeusia, or transient peripheral neuropathy. Both ciprofloxacin and metronidazole are effective in treating acute pouchitis with significant reduction of the PDAI scores. Ciprofloxacin produces a greater reduction in the PDAI and a greater improvement in symptom and endoscopy scores, and is better tolerated than metronidazole. Ciprofloxacin should be considered as one of the first-line therapies for acute pouchitis.

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.

OBJECTIVE: To describe the design and first-round survey results of a trial of intensive sexually transmitted disease (STD) control to reduce HIV-1 incidence. STUDY DESIGN: Randomized, controlled, community-based trial in Rakai District, Uganda. METHODS: In this ongoing study, 56 communities were grouped into 10 clusters designed to encompass social/sexual networks; clusters within blocks were randomly assigned to the intervention or control arm. Every 10 months, all consenting resident adults aged 15-59 years are visited in the home for interview and sample collection (serological sample, urine, and, in the case of women, self-administered vaginal swabs). Sera are tested for HIV-1, syphilis, gonorrhea, chlamydia, trichomonas and bacterial vaginosis. Following interview, all consenting adults are offered directly observed, single oral dose treatment (STD treatment in the intervention arm, anthelminthic and iron-folate in the control arm). Treatment is administered irrespective of symptoms or laboratory testing (mass treatment strategy). Both arms receive identical health education, condom and serological counseling services. RESULTS: In the first home visit round, the study enrolled 5834 intervention and 5784 control arm subjects. Compliance with interview, sample collection and treatment was high in both arms (over 90%). Study arm populations were comparable with respect to sociodemographic and behavioral characteristics, and baseline HIV and STD rates. The latter were high: 16.9% of all subjects were HIV-positive, 10.0% had syphilis, and 23.8% of women had trichomonas and 50.9% had bacterial vaginosis. CONCLUSIONS: Testing the effects of STD control on AIDS prevention is feasible in this Ugandan setting.

In the present report, five selected periodontal patients were treated for 1 week with metronidazole. Two of the patients had their teeth scales and root-planed the week they received metronidazole. Prior to treatment, B. asaccharolyticus accounted for 41% of the cultivable isolates and the spirochetes averaged 29% of the microscopic count in plaque removed from each of four pockets per patient. The presence of these elevated proportions of periodontopathic bacteria combined with the presence of periodontal pockets and attachment loss suggested that the patients were in a state of an active infectious process involving primarily anaerobic bacteria. If this be the case, then antimicrobial therapy directed against these anaerobes wih metronidazole was indicated. The 1-week treatment with metronidazole significantly reduced the proportions of these organisms for up to 6 months after treatment. Coincident with these findings was an improvement in the clinical parameters, especially in those sites that initially had greater than 5 mm pocket or attachment loss. These sites showed a 2 mm or more reduction in pocket depth and an almost 2 mm gain in apparent attachment that was evident 6 months after treatment. The results obtained were in only five patients. However, the magnitude of improvement suggests that antimicrobial therapy directed against anaerobic organisms may be a valuable adjunct to periodontal therapy.