Cliodna McNulty

Diagnosis of Helicobacter pylori Infection

When an endoscopy is performed, it now becomes easier to observe indirect evidence of the presence of a Helicobacter pylori infection, given the progress of new methods including magnifying narrow band imaging or confocal laser endomicroscopy. Out of the biopsy‐based tests, the novel original method proposed concerned culture in a broth medium with or without antibiotics and ELISA detection of H. pylori. New stool antigen tests are still appearing with no major improvement in comparison with the monoclonal‐based tests already on the market. The combination of pepsinogen detection to H. pylori serology is now more and more evaluated to detect preneoplastic lesions.

Use of an electronic nose system for diagnoses of urinary tract infections

The use of volatile production patterns produced by bacterial contaminants in urine samples were examined using electronic nose technology. In two experiments 25 and 45 samples from patients were analysed for specific bacterial contaminants using agar culture techniques and the major UTI bacterial species identified. These samples were also analysed by incubation in a volatile generation test tube system for 4-5 h. The volatile production patterns were then analysed using an electronic nose system with 14 conducting polymer sensors. In the first experiment analysis of the data using a neural network (NN) enabled identification of all but one of the samples correctly when compared to the culture information. Four groups could be distinguished, i.e. normal urine, Escherichia coli infected, Proteus spp. and Staphylococcus spp. In the second experiment it was again possible to use NN systems to examine the volatile production patterns and identify 18 of 19 unknown UTI cases. Only one normal patient sample was mis-identified as an E. coli infected sample. Discriminant function analysis also differentiated between normal urine samples, that infected with E. coli and with Staphylococcus spp. This study has shown the potential for early detection of microbial contaminants in urine samples using electronic nose technology for the first time. These findings will have implications for the development of rapid systems for use in clinical practice.

Helicobacter pylori test and treat versus proton pump inhibitor in initial management of dyspepsia in primary care: multicentre randomised controlled trial (MRC-CUBE trial)

Objective To determine the cost effectiveness of Helicobacter pylori “test and treat” compared with empirical acid suppression in the initial management of patients with dyspepsia in primary care. Design Randomised controlled trial. Setting 80 general practices in the United Kingdom. Participants 699 patients aged 18-65 who presented to their general practitioner with epigastric pain, heartburn, or both without “alarm symptoms” for malignancy. Intervention H pylori 13C urea breath test plus one week of eradication treatment if positive or proton pump inhibitor alone; subsequent management at general practitioner’s discretion. Main outcome measures Cost effectiveness in cost per quality adjusted life year (QALY) (EQ-5D) and effect on dyspeptic symptoms at one year measured with short form Leeds dyspepsia questionnaire. Results 343 patients were randomised to testing for H pylori, and 100 were positive. The successful eradication rate was 78%. 356 patients received proton pump inhibitor for 28 days. At 12 months no significant differences existed between the two groups in QALYs, costs, or dyspeptic symptoms. Minor reductions in costly resource use over the year in the test and treat group “paid back” the initial cost of the intervention. Conclusions Test and treat and acid suppression are equally cost effective in the initial management of dyspepsia. Empirical acid suppression is an appropriate initial strategy. As costs are similar overall, general practitioners should discuss with patients at which point to consider H pylori testing. Trial registration Current Controlled Trials ISRCTN87644265.

Detection of Campylobacter pylori by the biopsy urease test: an assessment in 1445 patients.

The presence of C pylori infection was determined in 1445 patients undergoing upper gastrointestinal endoscopy over a 12 month period. The presence of C pylori was detected in gastric mucosal biopsy specimens by the biopsy urease test, microscopy (Gram stained smears and histology) and culture. Two media were used for the biopsy urease test: Christensens urea broth (for the first 600 patients) and the Christensens urea broth modified by increasing the concentration of phenol red and omitting the nutrients, glucose and peptone (for the remaining patients). Both the Christensens urea broth and modified urea broth were almost 100% specific when compared with detection of C pylori by Gram, culture and histopathology. The modified broth was more sensitive (96% sensitivity compared with culture) than the Christensens broth (92% sensitivity) but this difference was not statistically significant. The modified broth gave significantly more positive results (58%) in less than 30 minutes than the Christensens broth (48%). Seventy four per cent of positive results were available in less than two hours. Specimens from patients with extensive C pylori infection gave more rapid results: 86% of specimens that yielded a profuse growth of C pylori and 76% that contained numerous organisms on histological sections had a positive urease test in less than one hour. There was no significant difference between the specificity and sensitivity of our modified urea broth and the other modified broths described in the literature. This test is a cheap and rapid alternative to the diagnosis of C pylori by Gram stained smears or culture.

The significance of cagA + Helicobacter pylori in reflux oesophagitis

BACKGROUND Helicobacter pylori is a gastroduodenal pathogen associated with ulceration, dyspepsia, and adenocarcinoma. Recent preliminary studies have suggested that H pylori may be protective for oesophageal adenocarcinoma. In addition, strains ofH pylori identified by the presence of the cytotoxin associated gene A (cagA) are shown to have a significant inverse association with oesophageal adenocarcinoma. Given that cagA + H pylori may protect against oesophageal carcinoma, these strains may be protective for oesophagitis, a precursor of oesophageal carcinoma. AIMS The aim of this study was to investigate the association betweencagA + H pylori and endoscopically proved oesophagitis. PATIENTS The study group included 1486 patients attending for routine upper gastrointestinal tract endoscopy. METHODS At endoscopy the oesophagus was assessed for evidence of reflux disease and graded according to standard protocols. Culture and histology of gastric biopsy specimens determined H pylori status. The prevalence of cagA was identified by an antibody specific ELISA (Viva Diagnostika, Germany). RESULTS H pylori was present in 663/1485 (45%) patients and in 120/312 (38%) patients with oesophagitis. Anti-CagA antibody was found in 499/640 (78%) H pylori positive patients. Similarly, anti-CagA antibody was found in 422/521 (81%) patients with a normal oesophagus and in 42/60 (70%) with mild, 24/35 (69%) with moderate, and 11/24 (46%) with severe oesophagitis. The risk of severe oesophagitis was significantly decreased for patients infected withcagA + H pylori after correction for confounding variables (odds ratio 0.57, 95% confidence interval 0.41–0.80; p=0.001). CONCLUSIONS These results suggest that infection bycagA + H pylori may be protective for oesophageal disease.

Antibacterial prescribing and antibacterial resistance in English general practice: cross sectional study.

Abstract Objective: To quantify the relation between community based antibacterial prescribing and antibacterial resistance in community acquired disease. Design: Cross sectional study of antibacterial prescribing and antibacterial resistance of routine isolates within individual practices and primary care groups. Setting: 405 general practices (38 groups) in south west and north west England. Main outcome measures: Correlation between antibacterial prescribing and resistance for urinary coliforms and Streptococcus pneumoniae. Results: Antibacterial resistance in urinary coliform isolates is common but the correlation with prescribing rates was relatively low for individual practices (ampicillin and amoxicillin rs=0.20, P=0.001; trimethoprim rs=0.24, P=0.0001) and primary care groups (ampicillin and amoxicillin rs=0.44, P=0.05; trimethoprim rs=0.31, P=0.09). Regression coefficients were also low; a practice prescribing 20% less ampicillin and amoxicillin than average would have about 1% fewer resistant isolates (0.94/100; 95% confidence interval 0.02 to 1.85). Resistance of S pneumoniae to both penicillin and erythromycin remains uncommon, and no clear relation with prescribing was found. Conclusions: Routine microbiological isolates should not be used for surveillance of antibacterial resistance in the community or for monitoring the outcome of any change in antibacterial prescribing by general practitioners. Trying to reduce the overall level of antibiotic prescribing in UK general practice may not be the most effective strategy for reducing resistance in the community. What is already known on this topic The probability of an individual hosting a resistant organism is increased by recent use of an antibacterial drug Correlation between antibacterial prescribing and coliform resistance in routine microbiological samples from the community has been reported in one study What this study adds In English general practice, there are significant but low correlations between antibacterial prescribing and resistance in routine isolates of urinary coliforms Substantial differences in prescribing between high and low prescribing practices are associated with only small differences in resistance Improved methods of assessing national antimicrobial resistance are required

Prevention and control of multi-drug-resistant Gram-negative bacteria: recommendations from a Joint Working Party

Multi-drug-resistant (MDR) Gram-negative bacterial infections have become prevalent in some European countries. Moreover, increased use of broad-spectrum antimicrobial agents selects organisms with resistance and, by increasing their numbers, increases their chance of spread. This report describes measures that are clinically effective for preventing transmission when used by healthcare workers in acute and primary healthcare premises. Methods for systematic review 1946–2014 were in accordance with SIGN 501 and the Cochrane Collaboration;2 critical appraisal was applied using AGREEII.3 Accepted guidelines were used as part of the evidence base and to support expert consensus. Questions for review were derived from the Working Party Group, which included patient representatives in accordance with the Patient Intervention Comparison Outcome (PICO) process. Recommendations are made in the following areas: screening, diagnosis and infection control precautions including hand hygiene, single-room accommodation, and environmental screening and cleaning. Recommendations for specific organisms are given where there are species differences. Antibiotic stewardship is covered in a separate publication.

Clinical score and rapid antigen detection test to guide antibiotic use for sore throats: randomised controlled trial of PRISM (primary care streptococcal management)

Objective To determine the effect of clinical scores that predict streptococcal infection or rapid streptococcal antigen detection tests compared with delayed antibiotic prescribing. Design Open adaptive pragmatic parallel group randomised controlled trial. Setting Primary care in United Kingdom. Patients Patients aged ≥3 with acute sore throat. Intervention An internet programme randomised patients to targeted antibiotic use according to: delayed antibiotics (the comparator group for analyses), clinical score, or antigen test used according to clinical score. During the trial a preliminary streptococcal score (score 1, n=1129) was replaced by a more consistent score (score 2, n=631; features: fever during previous 24 hours; purulence; attends rapidly (within three days after onset of symptoms); inflamed tonsils; no cough/coryza (acronym FeverPAIN). Outcomes Symptom severity reported by patients on a 7 point Likert scale (mean severity of sore throat/difficulty swallowing for days two to four after the consultation (primary outcome)), duration of symptoms, use of antibiotics. Results For score 1 there were no significant differences between groups. For score 2, symptom severity was documented in 80% (168/207 (81%) in delayed antibiotics group; 168/211 (80%) in clinical score group; 166/213 (78%) in antigen test group). Reported severity of symptoms was lower in the clinical score group (−0.33, 95% confidence interval −0.64 to −0.02; P=0.04), equivalent to one in three rating sore throat a slight versus moderate problem, with a similar reduction for the antigen test group (−0.30, −0.61 to −0.00; P=0.05). Symptoms rated moderately bad or worse resolved significantly faster in the clinical score group (hazard ratio 1.30, 95% confidence interval 1.03 to 1.63) but not the antigen test group (1.11, 0.88 to 1.40). In the delayed antibiotics group, 75/164 (46%) used antibiotics. Use of antibiotics in the clinical score group (60/161) was 29% lower (adjusted risk ratio 0.71, 95% confidence interval 0.50 to 0.95; P=0.02) and in the antigen test group (58/164) was 27% lower (0.73, 0.52 to 0.98; P=0.03). There were no significant differences in complications or reconsultations. Conclusion Targeted use of antibiotics for acute sore throat with a clinical score improves reported symptoms and reduces antibiotic use. Antigen tests used according to a clinical score provide similar benefits but with no clear advantages over a clinical score alone. Trial registration ISRCTN32027234

Developing e-Bug web games to teach microbiology

As a complement to the e-Bug teaching pack, two e-Bug games were developed to provide content that aimed to entertain as well as to educate. A set of agreed learning outcomes (LOs) were provided by the scientific partners of the e-Bug Project and the games were developed using user-centred design techniques (the needs, wants and limitations of the potential game players were assessed at each stage of the design process). The e-Bug games were designed for two age groups: Junior (9-12 year olds); and Senior (13-15 year olds). A study using focus groups was done to gain an understanding as to the types of games enjoyed by the target users. According to the preliminary study, the Junior Game was developed as a platform game and the Senior Game was developed as a story-based detective game. The Junior Game consists of five levels, each associated with a set of LOs. Similarly, the Senior Game consists of four missions, each comprising five stages using problem-based learning techniques and LOs. In this paper, the process of development for each game is described in detail and an illustration is provided of how each game level or mission addresses the target LOs. Development of the games used feedback acquired from children in four schools across the UK (Glasgow, London and two in Gloucester). The children were selected according to their willingness to participate. European Partners of the e-Bug Project also provided further support, translation and requests for modifications. The knowledge gained of LOs and further evaluation of the games is continuing, and preliminary results are in press. The final versions of the games, translated into 11 European languages, are available online via www.e-bug.eu.

The English antibiotic awareness campaigns: did they change the public's knowledge of and attitudes to antibiotic use?

OBJECTIVES To determine the effect of the 2008 English public antibiotic campaigns. METHODS English and Scottish (acting as controls) adults aged > or = 15 years were questioned face to face about their attitudes to and use of antibiotics, in January 2008 (1888) before and in January 2009 (1830) after the antibiotic campaigns. RESULTS Among English respondents, there was a small increase in recollection of campaign posters (2009 23.7% versus 2008 19.2%; P = 0.03), but this increase was only 2.3% higher in England than in Scotland. We did not detect any improvement in either England or Scotland, or any differences between England and Scotland in the understanding of the lack of benefit of antibiotics for coughs and colds, and we found no improvement in antibiotic use. We detected a significant increase in respondents retaining leftover antibiotics. Over 20% reported discussing antibiotics with their general practitioner (GP) or nurse in the year to January 2009. The offer of a delayed antibiotic prescription was reported significantly more often by English respondents (19% versus 8% Scottish in 2009; P = 0.01), and English respondents were advised to use other remedies for coughs and colds significantly more often in the year to January 2009 (12.7% in 2009 versus 7.4% in 2008; P < 0.001). CONCLUSIONS There is little evidence that the 2008 public antibiotic campaigns were effective. The use and visibility of future campaign materials needs auditing. A carefully planned approach that targets the public in GP waiting rooms and through clinicians in consultations may be a more effective way of improving prudent antibiotic use.