C. Keane

Long-term prospective study of Helicobacter pylori in nonulcer dyspepsia

Helicobacter pylori is present in up to 87% of patients with nonulcer dyspepsia. This study assessed the effect of eradicatingHelicobacter 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 andHelicobacter 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 persistentHelicobacter 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, persistentHelicobacter pylori infection was associated with more additional treatments than those with eradication (34/38 versus 4/37,P<0.001). These results suggest thatHelicobacter pylori plays an important role in the symptoms of nonulcer dyspepsia.

Metronidazole Resistance Reduces Efficacy of Triple Therapy and Leads to Secondary Clarithromycin Resistance

There has been a significant increase in theprevalence of H. pylori resistance to metronidazole inrecent years, while clarithromycin resistance is stillrelatively rare. In this study we assessed: (1) the effect of primary H. pylori resistance tometronidazole and clarithromycin on the clinicalefficacy of a one-week regimen consisting of omeprazole,metronidazole, and clarithromycin; and (2) the rate of acquisition of secondary antimicrobialresistance after treatment failure. Eighty-sevenpatients with duodenal ulceration or nonulcer dyspepsiawere included in the study. The primary metronidazoleand clarithromycin resistance rates were 35.6% and3.4%, respectively (all three pretreatmentclarithromycin resistant strains had concurrentmetronidazole resistance). H. pylori was eradicated in81.6% of patients. The eradication rate for fullysensitive isolates was 98.2% (55/56) but wassignificantly reduced to 57.1% (16/28) for isolates thatwere resistant to metronidazole alone and 0% (0/3) incases of dual resistance (P < 0.001). Secondaryresistance to clarithromycin was acquired in 58.3% ofcases of treatment failure. In areas of high prevalenceof primary metronidazole resistance, this is asignificant cause of treatment failure with this tripletherapy regimen. This leads to the selection of strainswith dual resistance that are difficult to eradicate andmay contribute to an increase in the prevalence of clarithromycin resistance. In such areas analternative first-line treatment should beprescribed.

Recurrence of Helicobacter pylori infection after successful eradication : Nature and possible causes

Recurrence of Helicobacter pylori infectionafter successful eradication occurs and is associatedwith relapse of gastroduodenal diseases. The aims ofthis paper were to assess the incidence and identify the nature and possible causes of recurrence ofthe infection. A broad-based Medline search wasperformed to identify all related publicationsaddressing recurrence of the infection between 1986 and1995. The 12-month recurrence rate varied among thedifferent studies from 0 to 41.5%. A few studies showed18- to 24-month recurrence rates, which ranged between0 and 21.4%. Limited data, obtained using molecular fingerprinting techniques, have shown that inmost cases recurrence is due to recrudescence of theoriginal strain; a few cases appear to be due toreinfection with a new strain. Recrudescence is mostlikely during the first 12 months after apparenteradication. Despite the high sensitivity andspecificity of the available individual tests fordetecting H. pylori infection in untreated patients, notechnique alone is sensitive enough to monitoreradication when the four-week-rule definition foreradication is used. A combination of two or moretechniques increases sensitivity. Sensitivity andspecificity are increased when biopsies are taken from bothgastric antrum and corpus. The best treatments have thelowest recurrence rates and recurrence is rare when theeradication rate is over 90%. Individual susceptibility and reexposure to H. pylori are suggested astwo major causes of reinfection.

Increased expression of Fcγ receptors on neutrophils and monocytes may reflect ongoing bacterial infection

The Fc gammaR receptors for IgG, Fc gammaRI, Fc gammaRII and Fc gammaRIII were measured on neutrophils and monocytes from 36 patients suspected of systemic infection. These results were compared with 30 blood donor controls to assess the level of expression as an early indicator of bacterial infection. Fc gammaRI expression on neutrophils was found to be significantly increased from patients with systemic or localised infections, when compared to non-infected patient group, i.e., patients with no cultural evidence of bacterial infections, (p=0.02, p=0.04) or normal controls (p<0.0001, p=0.0005). Fc gammaRI expression on monocytes was also significantly increased in both of the infected groups compared to normal controls (p<0.0001, p=0.001); however, no significant difference could be seen when compared with the non-infected patients. Fc gammaRIII was found to be significantly increased on a subset of monocytes in patients with systemic or localised infections compared to the non-infected group (p=0.009, p=0.006) and compared to the normal controls (p=0.009, p=0.003). Infections caused by gram-negative bacilli induced a higher Fc gammaR response than infection with either streptococci or staphylococci. These data suggest that the measurement of Fc gammaRI on neutrophils and Fc gammaRIII on monocytes may be a useful rapid indicator of bacterial infection.

Clinical efficacy of triple therapy in Helicobacter pylori-associated duodenal ulcer

Objective: To evaluate a triple treatment regimen of colloidal bismuth subcitrate (CBS), metronidazole and tetracycline in eradicating metronidazole resistant Helicobacter pylori in patients with duodenal ulcer and to assess interaction between metronidazole and tetracycline against H. pylori in vitro. Design: Eighty-nine patients with H. pylori infection and duodenal ulcer disease were treated with CBS 120 mg four times daily for 4 weeks, metronidazole 400 mg three times daily and tetracycline 500 mg three times daily for the first week. H. pylori was cultured and susceptibility to metronidazole and tetracycline assessed before and 4 weeks after treatment. In vitro interaction between metronidazole and tetracycline against H. pylori was evaluated with a checkerboard technique. Results: The triple therapy healed duodenal ulcer in 90.7% (59 out of 65) of patients with metronidazole sensitive strains and 79.2% (19 out of 24) of those with resistant strains (P > 0.05). H. pylori was eradicated in 92.3% (60 out of 65) of patients with metronidazole sensitive strains and in 62.5% (15 out of 24) with metronidazole resistant strains (P < 0.001). Healing of duodenal ulcer and improvement of antral inflammation was associated with eradication of the organism. Side effects were negligible. Synergism was observed against seven (30.4%) of 23 strains tested. Conclusions: The triple therapy with CBS, metronidazole and tetracycline for 1 week is effective in eradicating H. pylori. Resistance to metronidazole reduces, although not completely, the efficacy of triple therapy. Evaluation of in vitro interaction between antimicrobials may be helpful in chosing multiple chemotherapy for eradicating H. pylori.

Prevalence of metronidazole-resistant helicobacter pylori in dyspeptic patients

SummarySusceptibility to metronidazole of 213 clinical strains ofH. pylori from dyspeptic patients was determined by a plate dilution method. Seventy two (33.8%) of the strains were resistant to metronidazole (MIC > 8 mg/L), 20 of these were from 24 patients who had received previously metronidazole (83.3%), giving a primary (pretreatment) resistance rate of 27.5% (52/189). The resistance rate was higher in women than in men, especially aged 50 to 59 years old (43.6% vs 23.3%, p<0.001). The resistance rate was lower in patients at 60 or over (9.8%), but similar between the younger patients groups (38.8% - 49.0%). There was no difference in the resistance rate between peptic ulcer disease (32.6%) and nonulcer dyspepsia (34.7%). These data indicated that metronidazole resistance inH. pylori is absolutely associated with previous use of the drug, and the higher resistance rate in women may be due to the more frequent prescription of the drug for their gynaecological infection or operation. Therefore, testing of susceptibility ofH. pylori to metronidazole is important. A new susceptibility testing technique, the E-test was evaluated in this study and found to give comparable results to the plate dilution method and also had the advantage of being simple to perform.

Pre-formed urease activity of Helicobacter pylori as determined by a viable cell count technique-clinical implications

The pre-formed urease activity of three NCTC reference strains and five clinical isolates of Helicobacter pylori was determined at room temperature (21 degrees C) and 37 degrees C by a viable cell count technique with a conventional urea slope test (Christensens agar) as well as the commercial CLO-test. The urease activity of two gastroduodenal commensals, Proteus mirabilis and Klebsiella pneumoniae, was also tested. H. pylori strains produced positive reactions with viable cell counts of 10(6)-10(8) cfu within 30 min and with counts of 10(3)-10(6) cfu within 2 h. For some strains, smaller numbers of organisms were needed with the CLO-test than with the conventional test, and incubation of the CLO-test strips at 37 degrees C slightly decreased the number of organisms required for positive results. P. mirabilis produced a positive result on urea slopes with an initial inoculum of 10(7)-10(8) cfu at 2 h, but no positive reaction occurred for K. pneumoniae at 12 h, even with an initial inoculum of 10(11) cfu. However, both P. mirabilis and K. pneumoniae gave a positive result after incubation for 24 h with initial inocula of < 10(1) cfu and 10(3)-10(4) cfu respectively. Incubation at 37 degrees C significantly reduced the inoculum size of these organisms required for a positive result after incubation for 4 h when tested with the slopes, but not with the CLO-test. These findings indicate that H. pylori possesses much greater pre-formed urease activity than P. mirabilis and K. pneumoniae. False negative results for clinical detection of H. pylori in gastroduodenal biopsies may be due to small numbers of organisms, especially after treatment with antimicrobial agents, and false positive results may arise from gastroduodenal commensals or contaminants.

Short report: short-term triple therapy for H. pylori-associated duodenal ulcer disease

Thirty consecutive patients with endoscopically proven duodenal ulceration who had Helicobacter pylori infection on culture and histology, were treated with tripotassium dicitrato bismuthate (1 tablet q.d.s., 400 mg metronidazole t.d.s. and 500 mg tetracycline t.d.s. for one week, followed by the bismuth salt for a further 3 weeks. All patients were endoscoped at entry and 4 weeks after cessation of treatment, to check for ulcer healing and H. pylori eradication. Two antral biopsies were taken at each endoscopy for histological and microbiological evidence of H. pylori infection. Complete healing of duodenal ulcers was observed in 27/30 patients (90%). Gastritis improved or completely resolved in 26 patients. Eradication of H. pylori was achieved in 27 patients. Of the three patients who failed to heal, two were H. pylori‐positive at follow‐up and one was H. pylori‐negative.

Culture of Helicobacter pylori under aerobic conditions on solid media

The aim of the present study was to cultureHelicobacter pylori under aerobic conditions and to investigate the characteristics of the organism when cultured aerobically. Most (22 of 23) of theHelicobacter pylori isolates grew under aerobic conditions, but with reduced viable cell counts. Blood agar was more suitable than chocolate agar. The morphological and enzymatic characteristics as well as the protein profiles of each organism were identical under aerobic and microaerophilic conditions. However, haemolysis ofHelicobacter pylori was delayed under aerobic conditions. The MIC of metronidazole was slightly lower for some strains under aerobic conditions. These findings indicate thatHelicobacter pylori is not only a microaerophilic organism but also adapts to aerobic conditions, which may have some important implications in microbiological and epidemiological studies.

Determination of the optimal transport system for Helicobacter pylori cultures

A range of solid and liquid media was evaluated for the ability to maintain survival of Helicobacter pylori strains under different conditions. Chocolate agar slopes maintained survival of most strains for longer than 3 days, some strains surviving for up to 9 days, despite a decreased number of viable cells. Temperature and atmosphere did not significantly influence the performance of these slopes. The BBL Campy Pouch system also achieved a considerable recovery rate of H. pylori after storage for 3 days at the same range of temperatures. Brain-heart infusion broth with horse serum was superior among the liquid media tested, maintaining the viability of H. pylori for c. 3 days at temperatures ranging from -4 degrees C to 21 degrees C. Chocolate agar slopes are recommended as suitable for transport of H. pylori strains.