House dust mites as potential carriers for IgE sensitization to bacterial antigens.

BACKGROUND: IgE reactivity to antigens from Gram-positive and Gram-negative bacteria is common in patients suffering from respiratory and skin manifestations of allergy, but the routes and mechanisms of sensitization are not fully understood. The analysis of the genome, transcriptome and microbiome of house dust mites (HDM) has shown that Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) species are abundant bacteria within the HDM microbiome. Therefore, our aim was to investigate whether HDM are carriers of bacterial antigens leading to IgE sensitization in patients suffering from atopic dermatitis. METHODS: Plasma samples from patients with AD (n = 179) were analysed for IgE reactivity to a comprehensive panel of microarrayed HDM allergen molecules and to S. aureus and E. coli by IgE immunoblotting. Antibodies specific for S. aureus and E. coli antigens were tested for reactivity to nitrocellulose-blotted extract from purified HDM bodies, and the IgE-reactive antigens were detected by IgE immunoblot inhibition experiments. IgE antibodies directed to bacterial antigens in HDM were quantified by IgE ImmunoCAP™ inhibition experiments. RESULTS: IgE reactivity to bacterial antigens was significantly more frequent in patients with AD sensitized to HDM than in AD patients without HDM sensitization. S. aureus and E. coli antigens were detected in immune-blotted HDM extract, and the presence of IgE-reactive antigens in HDM was demonstrated by qualitative and quantitative IgE inhibition experiments. CONCLUSION: House dust mites (HDM) may serve as carriers of bacteria responsible for the induction of IgE sensitization to microbial antigens.

Comprehensive evaluation of chemiluminescent immunoassays for the laboratory diagnosis of Clostridium difficile infection.

For the microbiological diagnosis of a Clostridium (C.) difficile infection (CDI), a two-test algorithm consisting of a C. difficile glutamate dehydrogenase (GDH)-immunoassay followed by a toxin-immunoassay in positive cases is widely used. In this study, two chemiluminescent immunoassays (CLIAs), one for GDH and the other for the toxins A and B, have been evaluated systematically using appropriate reference methods. Three-hundred diarrhoeal stool specimens submitted for CDI diagnosis were analysed by the LIAISON CLIAs (DiaSorin). Toxigenic culture (TC) and cell cytotoxicity assay (CCTA) were used as "gold standard" reference methods. In addition, GDH and toxin A and B enzyme immunoassays (EIAs), C. diff Chek-60 and toxin A/B II (TechLab), and the Cepheid Xpert C. difficile polymerase chain reaction (PCR) were performed. C. difficile was grown in 42 (14%), TC was positive in 35 (11.7%) and CCTA in 25 (8.3%) cases. CLIAs were more sensitive but less specific than the respective EIAs. Using culture as reference, the sensitivity of the GDH CLIA was 100%. In comparison to CCTA sensitivity, specificity, positive predictive value and negative predictive value of the two-test algorithm were 88, 99.3, 91.7 and 98.9% by CLIAs and 72, 99.6, 94.7 and 97.5% by EIAs. Discrepant results by CLIAs were more frequent than that by EIAs (9% vs. 6.3%); in those cases, PCR allowed for the accurate detection of toxigenic strains. Due to performance characteristics and testing comfort, CLIAs in combination with PCR represent a favourable option for the rapid laboratory C. difficile diagnostics.

Immunoglobulin E antibody reactivity to bacterial antigens in atopic dermatitis patients.

BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory skin disease affecting up to 20% children and 9% adults world-wide. AD patients are often sensitized against a broad variety of allergens and more than 90% of them suffer from skin superinfections with Staphylococcus aureus. OBJECTIVE: In this study, we searched for the presence of specific IgE antibodies against S. aureus and Escherichia coli antigens in AD patients. METHODS: Sera from AD patients (n=79), patients suffering only from allergic rhinoconjunctivitis (n=41) or allergic asthma (n=37) were tested for IgE reactivity to nitrocellulose-blotted S. aureus, E. coli and gut bacterial antigens. IgE-reactive bacterial antigens were affinity purified and identified by mass spectrometry. RESULTS: More than 30% of AD patients but not patients suffering only from allergic rhinoconjunctivitis and asthma or non-allergic persons exhibited IgE binding to several protein antigens among them DNA-binding and ribosomal proteins and flagellin. Patients with severe skin manifestations showed more frequently IgE reactivity to S. aureus compared with AD patients with mild symptoms. Positive immediate and late skin test reactions could be induced in sensitized AD patients with S. aureus extract. CONCLUSION AND CLINICAL RELEVANCE: Specific IgE reactivities against a variety of bacterial antigens were observed in a subgroup comprising a third of AD patients and may contribute to allergic inflammation.

Evaluation of a novel internally controlled real-time PCR assay targeting the 16S rRNA gene for confirmation of Neisseria gonorrhoeae infections.

A novel HybProbe real-time LightCycler PCR assay was developed for confirmation of Neisseria gonorrhoeae in samples positive according to the COBAS AMPLICOR Chlamydia trachomatis/Neisseria gonorrhoeae PCR assay. The new assay amplifies 375 bp of the N. gonorrhoeae 16S rRNA gene and includes an internal amplification control introduced during DNA purification. The assay had 100% specificity because of the high specificity of the HybProbes and primers. Other Neisseria spp. failed to generate positive crossing-point values and melting peaks. The analytical sensitivity for N. gonorrhoeae DNA was 0.5 fg/PCR, corresponding to 0.3 CFU/PCR. Sensitivity was not impaired in the presence of higher DNA concentrations (>or=1000-fold) from Neisseria spp. other than N. gonorrhoeae. The sensitivity was similar to that reported for the COBAS AMPLICOR assay with cervical swab samples. To assess its clinical applicability as a confirmatory test, 38 (2.9%) of 1313 swabs that were positive according to the COBAS AMPLICOR assay were tested using the new in-house assay and the commercially available GenFlow Neisseria test. Twenty-one samples negative according to COBAS AMPLICOR also underwent confirmatory testing. Both confirmatory tests yielded identical results; the 21 negative samples remained negative, and only 11 (28.9%) of the samples positive according to COBAS AMPLICOR were positive after retesting, suggesting a low prevalence (0.84%) of N. gonorrhoeae infection in the study population. These data suggest that the novel real-time PCR assay is an excellent and easy to interpret confirmatory test for the existing COBAS AMPLICOR assay for N. gonorrhoeae.

Evaluation of a protocol for molecular broad-range diagnosis of culture-negative bacterial infections in clinical routine diagnosis.

AIM: Introduction of a protocol for broad-range diagnosis of bacterial infections, which remain negative in culture. METHODS AND RESULTS: The new TaqMan real-time PCR assay amplifies part of the 16S rRNA gene. Species are identified by subsequent sequencing and phylogenetic blast analysis. The analytical sensitivity showed to be 50 fg DNA per PCR. The lowest detectable bacterial cell concentration in blood was 1000 CFU per 200 mul EDTA-blood. The utility in clinical routine diagnosis was evaluated by testing 136 clinical specimens. Bacterial pathogens were detected in 33 samples (24.3%) either by culture or molecular diagnosis. In 10 culture negative cases, pathogens such as Mycoplasma timone/orale, Ureaplasma parvum/urealyticum, Treponema pallidum, different streptococci and staphylococci were identified by molecular diagnosis only. CONCLUSIONS: The introduced broad-range real-time PCR protocol showed to be useful in the clinical routine in cases where bacterial infection was highly anticipated but culture remained negative. However, the obtained data have to be always interpreted with caution and in conjunction with the clinical data, crossing-point values and with the Blast result of both the sample and the controls. SIGNIFICANCE AND IMPACT OF THE STUDY: This work introduces a new and well-evaluated broad-range real-time PCR protocol for diagnosis of bacterial infections.

Prospective multicentre clinical study on inter- and intrapatient genetic variability for antimicrobial resistance of Helicobacter pylori.

OBJECTIVES: We report on a large prospective, multicentre clinical investigation on inter- and intrapatient genetic variability for antimicrobial resistance of Helicobacter pylori. METHODS: Therapy-naive patients (n = 2004) who had undergone routine diagnostic gastroscopy were prospectively included from all geographic regions of Austria. Gastric biopsy samples were collected separately from antrum and corpus. Samples were analysed by histopathology and real-time PCR for genotypic resistance to clarithromycin and quinolones. Clinical and demographic information was analysed in relation to resistance patterns. RESULTS: H. pylori infection was detected in 514 (26%) of 2004 patients by histopathology and confirmed in 465 (90%) of 514 patients by real-time PCR. PCR results were discordant for antrum and corpus in 27 (5%) of 514 patients, indicating inhomogeneous infections. Clarithromycin resistance rates were 17% (77/448) and 19% (84/455), and quinolone resistance rates were 12% (37/310) and 10% (32/334) in antrum and corpus samples, respectively. Combination of test results per patient yielded resistance rates of 21% (98/465) and 13% (50/383) for clarithromycin and quinolones, respectively. Overall, infection with both sensitive and resistant H. pylori was detected in 65 (14%) of 465 patients. CONCLUSIONS: Anatomically inhomogeneous infection with different, multiple H. pylori strains is common. Prospective clinical study design, collection of samples from multiple sites and microbiologic methods that allow the detection of coinfections are mandatory for collection of reliable data on antimicrobial resistance patterns in representative patient populations. (ClinicalTrials.gov identifier: NCT02925091).

Effects of tigecycline, linezolid and vancomycin on biofilms of viridans streptococci isolates from patients with endocarditis.

BACKGROUND: Endocarditis, and prosthetic valve endocarditis in particular, is a serious disease with high morbidity and mortality. We investigate the effects of tigecycline, linezolid and vancomycin on biofilms of viridans group streptococci (VGS) isolated from patients with definite native or prosthetic valve endocarditis. METHODS AND RESULTS: Ten of 20 VGS blood stream isolates from patients with endocarditis formed biofilms in the microtiter plate biofilm model. The minimal inhibitory concentrations (MIC) for tigecycline, linezolid and vancomycin were determined using the microdilution broth method. Biofilms were grown for 24 hours and were incubated with tigecycline, linezolid and vancomycin at increasing concentrations from 1-128x MIC of the isolate being tested. Biofilm thickness was quantified by measuring the optical density (OD) after dyeing it with crystal violet. The incubation of the biofilms with tigecycline, linezolid or vancomycin resulted in a significant reduction of OD compared to the control biofilm without antibiotic (p<0.05). The optical density ratio (Odr) decreased significantly at 2x MIC for tigecycline, and at 8x MIC for linezolid and vancomycin (p<0.05). Although biofilms persisted even at the highest antibiotic concentrations of 128x MIC, bacterial growth was eradicated starting at concentrations of 16x MIC for vancomycin and of 32x MIC for linezolid, but not for tigecycline, up to a concentration of 128x MIC. CONCLUSIONS: In the present study on viridans streptococci isolated from patients with endocarditis, tigecycline and linezolid reduced the density of the biofilms as effectively as vancomycin. However, linezolid and vancomycin were bactericidal at higher concentrations. Linezolid and vancomycin at very high doses may be useful in the treatment of biofilm-associated diseases caused by VGS infections.

Famotidine versus omeprazole in combination with clarithromycin and metronidazole for eradication of Helicobacter pylori--a randomized, controlled trial.

BACKGROUND: One-week low-dose triple therapy is currently considered the gold standard regimen for treatment of Helicobacter pylori infection. However, the mechanisms involved in the synergy between antibiotics and proton pump inhibitors are controversial. AIMS: To test the hypothesis that acid suppression represents the crucial mechanism by which the antibacterial activity of antibiotics can be enhanced, and to assess the impact of primary resistance on treatment outcome. METHODS: One hundred and twenty patients with H. pylori infection and duodenal ulcer, gastric ulcer or non-ulcer dyspepsia were randomly assigned to a 1 week course of either famotidine 80 mg b.d., clarithromycin 250 mg b.d. and metronidazole 500 mg b.d. (FCM group; n = 60) or omeprazole 20 mg o.d., clarithromycin 250 mg b.d. and metronidazole 500 mg b.d. (OCM group; n = 60). Gastroscopy was performed at baseline and 5 weeks after completion of treatment. H. pylori status was assessed by biopsy urease test, histology and culture. RESULTS: In the intention-to-treat analysis, eradication of H. pylori was achieved in 47 of 60 patients (78%; 95% CI: 66-88%) in the FCM group, compared to 44 of 60 patients (73%; 95% CI: 60-84%) in the OCM group (N.S.). Using per protocol analysis, eradication therapy was successful in 47 of 52 patients (90%; 95% CI: 79-97%) treated with FCM and 44 of 57 patients (77%; 95% CI: 64-87%) treated with OCM (N.S.). Primary metronidazole resistance was present in 27% and primary clarithromycin resistance in 8% of strains. Overall per protocol eradication rates in strains susceptible to both antibiotics and strains with isolated metronidazole resistance were 93% and 84%, respectively. No patient with clarithromycin resistance responded to treatment. CONCLUSIONS: High-dose famotidine and omeprazole, combined with clarithromycin and metronidazole, are equally effective for eradication of H. pylori. In 1-week low-dose triple therapy, metronidazole resistance has no major impact on eradication rates whereas clarithromycin resistance is associated with a poor treatment outcome.

Comparison of ELISA antigen preparations alone or in combination for serodiagnosing Helicobacter pylori infections.

The immunoglobulin G antibody response to Helicobacter pylori was assessed in 78 patients with non-ulcer dyspepsia using five different antigen preparations. All patients were endoscoped and biopsied. The H pylori state was determined histologically on at least two endoscopic biopsy specimens using a modified Giemsa stain. The ultracentrifuged cell sonicate, acid glycine extract, and 120 kilodalton protein antigens were specific in diagnosing infection (95-98%), but had only moderate sensitivity (70-84%). By mixing either of the two complex antigens with the 120 kilodalton protein, the sensitivity of the test was increased to 97% without affecting the high specificity. The combination of ultracentrifuged sonicate or acid glycine extract with the 120 kilodalton protein therefore seems to be superior to the individual antigen preparations and is particularly suitable for the serodiagnosis of H pylori infection.

Hyperemesis gravidarum associated with Helicobacter pylori seropositivity.

OBJECTIVE: To test the hypothesis that infection with Helicobacter pylori is associated with hyperemesis gravidarum. METHODS: From January 1995 to November 1996 we enrolled 105 patients with hyperemesis gravidarum in a prospective study. The Helicobacter serum Immunoglobulin (Ig) G concentrations in these patients were compared with those in asymptomatic gravidas matched for week of gestation. RESULTS: Positive serum IgG concentrations were found in 95 of the 105 hyperemesis patients (90.5%) compared with 60 of 129 controls (46.5%). A chi2 test showed statistical significance (P < .001). The mean (+/-standard deviation) index percentages of the IgG titers were 74.2+/-23.6% in the hyperemesis group and 24.3+/-4.4% in the control group (P < .01, Student t test). CONCLUSION: Infection with H pylori may cause hyperemesis gravidarum.

Susceptibility testing of Candida species: comparison of NCCLS microdilution method with Fungitest.

Fungitest is a new commercially available and easy-to-perform breakpoint test system using six antifungal agents. We compared this test with a modified standard method described by the National Committee for Clinical Laboratory Standards (NCCLS). One hundred isolates of Candida species were tested with both methods. Based on the same breakpoints, the correlation of qualitative results between the reference method and Fungitest was high. Best results were obtained after incubation of Fungitest for 48 h. Overall agreement was high, an excellent correlation was given with amphotericin B and flucytosine (100% and 99%, respectively), whereas itraconazole showed only 86% concordance. When Fungitest was read after 24 h the agreement was lower ranging from 100% to 75%. Some of the breakpoints used with Fungitest differ from the breakpoints recommended by NCCLS, whereas others have not been elaborated by the NCCLS. The adaptation of Fungitest breakpoints to NCCLS and determination of further breakpoints have to be discussed before Fungitest can be recommended for routine use.

Effect of chlorhexidine-containing detergent, non-medicated soap or isopropanol and the influence of neutralizer on bacterial pathogenicity.

In handwashing experiments with Salmonella typhimurium the effect of chlorhexidine (CHX) on the pathogenicity of surviving bacteria was assessed with and without a neutralizer in a mouse model of infection. Without neutralizer the LD50 of CHX handwash fluids was raised. Neutralizer in suspensions of untreated bacteria caused a reduction of LD50 up to 1.2 logs. Thus, in contrast to soap or alcohol, CHX without neutralizer exerted a slight 'depathogenizing' action and neutralizer a slight 'pathogenizing' effect in the experimental model used. However, in comparison to the efficiency of handwashing procedures which reduce the number of bacteria available for transfer by at least 3.0 to 4.2 logs, the size of these effects seems to be negligibly small and unpredictable. Therefore, the single most important parameter in assessing the potency of disinfectants remains the reduction of viable counts with time.

Bacterial contamination of dialysate in dialysis-associated endotoxaemia.

Bacteriological investigations and endotoxin (ET) determinations were performed during a routine haemodialysis session for six patients. The glucose free dialysate was prepared with untreated tap water. All patients were dialysed for 5 h. Pseudomonas aeruginosa was regularly isolated in numbers up to 10(7) cfu ml-1 from samples of the dialysate inflow, the dialysate site and the dialysate outflow. ET levels in the plasma of the patients increased continuously during haemodialysis and were always higher in the blood outflow line of the dialyzer than in the blood inflow. Despite the high bacterial counts in the dialysate and the increasing ET levels in the patients plasma neither bacteraemia nor fever was observed. The former is due to the impermeability of the dialyzer membrane for bacteria, the latter is explained by low pyrogenicity of P. aeruginosa endotoxin. Inspection of the dialyzer machines revealed that air-traps and heater-unit for the incoming (untreated) tap water before mixing with the dialysate concentrate were the only sites where high bacterial release was feasible, as this part of the machine escaped disinfection due to the construction of these devices. We recommend the regular disinfection of all parts of a dialyzer machine, including heating units, air traps and valves.

Serological tests for monitoring Helicobacter pylori eradication treatment.

Serological tests for the detection of Helicobacter pylori-specific antibodies are useful in epidemiological studies, as a pre-endoscopic screening procedure, and as therapeutic follow-up. For the latter application, they represent an alternative to invasive and expensive diagnostic methods such as endoscopy and breath test, respectively. However, serological tests are suitable only for long-term treatment monitoring in adults. As the significant reduction of specific antibodies, and not seronegativity by itself, is regarded as a criterion of therapeutic success, it is always necessary to establish the antibody kinetics. Enzyme-linked immunosorbent assay (ELISA) based tests are best suited for this. The most relevant antibody class to be detected is H. pylori-specific IgG. The main indication for employing serology is the therapeutic follow-up of patients who, on the whole, are free of complaints.

Amoxicillin for the treatment of Helicobacter pylori infection.

Amoxicillin is one of the most active antimicrobials against Helicobacter pylori in vitro, with a minimum inhibitory concentration (MIC) of < or = 0.01-0.1 mg/l. Thus far, neither primary nor secondary resistant strains have been found. Amoxicillin, which has a bactericidal effect on H. pylori, but is less inhibitory in the stationary growth phase and against cell-adherent or slowly growing H. pylori, probably has both topical and systemic activity. It is fairly acid stable and is less affected by gastric acidity than macrolides. Nevertheless, its activity in vivo is considerably enhanced when it is given concomitantly with proton pump inhibitors. Several amoxicillin-containing treatment regimes have yielded H. pylori eradication rates of > or = 90%. Of particular interest are 1-week treatment regimens containing amoxicillin + clarithromycin + omeprazole, or amoxicillin + metronidazole + omeprazole, as well as a 1-h topical therapy developed in Japan.

Clarithromycin or amoxycillin plus high-dose ranitidine in the treatment of Helicobacter pylori-positive functional dyspepsia.

OBJECTIVE: This study was intended to investigate the effect of ranitidine in dual anti-Helicobacter pylori therapy. Simultaneously, it was to evaluate the potential effect of H. pylori eradication on the symptomatology of H. pylori-positive dyspepsia. PATIENTS AND METHODS: Fifty-four patients with H. pylori infection and symptoms of non-ulcer dyspepsia were randomly assigned to treatment with either amoxycillin 500 mg four times daily plus ranitidine 300 mg four times daily, clarithromycin 500 mg twice daily plus ranitidine 300 mg twice daily, clarithromycin 500 mg four times daily plus ranitidine 300 mg twice daily or clarithromycin 500 mg four times daily plus ranitidine 300 mg four times daily for a period of 12 days. In addition, ranitidine 150 mg twice daily was given for a further 16 days. RESULTS: Eradication of H. pylori using the assigned treatments was achieved in 47% (seven out of 15), 50% (five out of 10), 70% (seven out of 10) and 77% (10 out of 13) of patients, respectively. Failure of therapy with clarithromycin was associated with primary or acquired resistance after treatment in 91% (10 out of 11). Symptom improvement was significant (P = 0.0001) and similar in all of the four treatment groups up to week 8. As regards H. pylori status, no differences in the mean symptom score improvement could be found between patients with eradication and those with persistent infection (12.3-7.0, P = 0.0001, n = 29 compared with 13.0-6.5, P = 0.004, n = 19). After 1 year the symptom score had increased both in patients with persistent H. pylori (9.1) and in those remaining free of infection (10.0). No reinfection could be found. CONCLUSION: These results suggest that clarithromycin plus high-dose ranitidine is a combination which achieves reasonably high H. pylori eradication rates. However, treatment failure inevitably leads to clarithromycin resistance. The improvement of non-ulcer dyspepsia symptoms during acute therapy is independent of H. pylori eradication. Long-term benefit of H. pylori eradication with respect to the symptoms of functional dyspepsia was not observed.

Impact of bacteria in dairy products and of the intestinal microflora on the genotoxic and carcinogenic effects of heterocyclic aromatic amines.

This article gives a short overview on the present state of knowledge of the effects of the intestinal microflora on the health hazards of heterocyclic aromatic amines (HAs). Results of single cell gel electrophoresis assays with conventional, germ free and human flora associated rats indicate that the presence of intestinal microorganisms strongly enhances the induction of DNA-damage in colon and liver cells by IQ. Furthermore, it was found that supplementation of the feed with Lactobacilli attenuates the induction of colon cancer by this same amine. These recent findings suggest that the intestinal microflora and lactic acid bacilli in dairy products strongly affect the health risks of HAs. Nevertheless, most previous experiments with HAs focused on the involvement of mammalian enzymes in the biotransformation of these compounds and only a few articles are available which concern interactions of bacteria with HAs. Some of these studies suggested that the formation of directly mutagenic hydroxy-metabolites of the amines by fecal bacteria might be an important activation pathway but it turned out that the hydroxy-derivative of IQ is not genotoxic in mammalian cells and does not cause colon cancer in laboratory rodents. There is some evidence that hydrolysis of HA-metabolites by bacterial ss-glucuronidase might play a role in the activation of HAs but experimental data are scarce and no firm conclusions can be drawn at present. The most important detoxification mechanism appears to be the direct binding of the HAs to the cell walls of certain bacterial strains contained in fermented foods. It was shown that these effects do also take place under physiologically relevant conditions. Overall, it seems that intestinal bacteria play a key role in the activation and detoxification of HAs which has been an area of research long ignored. The elucidation of these mechanisms may enable the development of biomarkers for colon cancer risk and nutritional strategies of protection.

Effect of omeprazole and amoxicillin plus metronidazole on the eradication of Helicobacter pylori and the healing of duodenal ulcer: comparison with a historical control.

BACKGROUND/AIMS: To test the hypothesis of equivalence of an omeprazole 7-day triple therapy without subsequent acid suppression and a historical ranitidine 12-day triple therapy (recruiting phase 1989-91) with subsequent acid suppression in their effect on the eradication of Helicobacter pylori (H. pylori) and the healing of duodenal ulcer. METHODOLOGY: Seventy-seven patients with H. pylori-positive duodenal ulcers received a 7-day treatment with amoxicillin 750 mg tid and metronidazole 500 mg tid. Additional omeprazole 20 mg or 40 mg once daily was given to 39 and 38 of the patients, respectively. Endoscopy was performed before treatment and four weeks after cessation of therapy. RESULTS: The cumulative intention-to-treat (ITT) H. pylori-eradication rate was 66% (51/77) as compared to 89% (46/52) for the historical control (p < 0.05). The corresponding ulcer healing rates were 90% (69/77) and 92% (48/52). Primary metronidazole resistance (PMR) had escalated from 10% to 27% within 6 years resulting in eradication rates of 84% for sensitive and 19% for resistant strains (p < 0.001). PMR could be demonstrated in 45% of all female, but only in 17% of the male patients (p < 0.05). In the patients with H. pylori eradication, the ulcers healed in 98% (50/51) as compared to 73% (19/26) in those with persistent infection (p < 0.005). Analysis based on the presence of PMR showed ulcer healing rates of 95% (53/56) for sensitive and 76% (16/21) for resistant strains (p < 0.05). Improvement of pain also showed a significant correlation with successful eradication. H. pylori-eradication, healing and symptom relief were similar in the omeprazole 20 mg and 40 mg groups. CONCLUSIONS: The effect of amoxicillin plus metronidazole plus antisecretory agent on the eradication of H. pylori has decreased markedly during the past 6 years due to the escalation of PMR. Doubling of the omeprazole dose does not affect outcome. Cure of the infection as well as metronidazole susceptibility enhance duodenal ulcer healing and symptom relief. Acid suppression following a successful 1-week anti-HP therapy is not required for duodenal ulcer treatment.

[Helicobacter pylori: pathogens, pathomechanisms and epidemiology]. / Helicobacter pylori: Erreger, Pathomechanismen und Epidemiologie.

H. pylori organisms are microaerophilic gram-negative curved or spiral bacteria that live in the mucus layer of the gastric epithelium. Since the discovery of H. pylori similar organisms have been found in humans (H. cinaedi, H. fennelliae, H. heilmanii) and animals. H. pylori causes chronic active gastritis and is an important factor in the development of peptic ulceration and gastric cancer. Narrow host range, tissue specificity and chronic inflammation are characteristic features. Putative virulence factors of H. pylori are structural components (flagella, adhesins...) extracellular bacterial products (urease, protease, phospholipase, cytotoxin...), induction of autoimmune reactions and the activation or stimulation of cellular products (PAF, interleukins, TNF alpha...). Colonization with H. pylori is common throughout the world; it is likely that one half of the world's population is infected. In developed countries few infections occur during childhood, whereas in developing countries most persons are infected by the age of 10 years. Socioeconomic factors seem to determine the age of acquisition. Person to person spread is the most likely form of transmission, but it is not clear whether this is fecal-oral or oral-oral. No non-human reservoir has been identified so far.

[Campylobacter pylori, gastritis and peptic ulcer]. / Campylobacter pylori, Gastritis und Ulcus pepticum.

In the course of routine gastroduodenoscopic examination of 218 patients bioptic mucosal specimens were examined bacteriologically for the presence of Campylobacter (C.) pylori. The organism was isolated from 52 out of 53 patients (98%) with duodenal ulcer, 7 out of 9 with gastric ulcer (78%), 24 out of 31 with mucosal erosions (77%), 10 out of 10 with duodenitis (100%), 16 out of 16 with chronic active gastritis (100%) and from 40 out of 73 patients (55%) with inactive chronic gastritis. By contrast, all specimens from 26 patients with endoscopically and histologically normal mucosa were negative for this bacterium. The rate of elimination of C. pylori from mucosal specimens was investigated as a first step towards studying the influence of antibiotic therapy upon healing of gastric and duodenal ulcers. For this purpose 30 patients with duodenal ulcers were treated either with ranitidine alone (15) or together with bacampicillin (15), which was shown to be highly active in studies with ampicillin in vitro. After 4 weeks the organism was still found in specimens from all patients treated with ranitidine alone, but also in 12 out of 15 patients given combined therapy. This result demonstrates that systemic antimicrobial chemotherapy with bacampicillin is insufficient to eradicate C. pylori from the stomach and the duodenum.