Genomic analysis of Helicobacter pylori in Australia: Antimicrobial resistance, phylogenetic patterns, and virulence factors.

BACKGROUND AND AIM: Rates of antimicrobial-resistant Helicobacter pylori infection are rising globally, but little is known about contemporary resistance patterns, virulence factors, and phylogenetic patterns of isolates within Australia. We aimed to characterize antimicrobial resistance and genetic mutations associated with adverse clinical outcomes. METHODS: Whole genome sequencing, culturing, and antibiotic sensitivity data for refractory H. pylori isolates at Australian centers were collected between 2013 and 2022. Phylogenetic origins, antibiotic resistance mutations, and virulence factors were examined with phenotypic resistance profiles. RESULTS: One hundred thirty-five isolates underwent culture, with 109 of these undergoing whole genome sequencing. Forty-three isolates were isolated from patients in South Australia and 66 from Western Australia. Isolates originated primarily from hpEurope (59.6%), hpEastAsia (25.7%), and hpNEAfrica (6.4%). Antimicrobial resistance to clarithromycin was seen in 85% of isolates, metronidazole in 52%, levofloxacin in 18%, rifampicin in 14%, and amoxicillin in 9%. Most isolates (59%) were multi-drug resistant. Resistance concordance between genetically determined resistance and phenotypic resistance was 92% for clarithromycin and 94% for levofloxacin. Analysis of virulence factors demonstrated cag pathogenicity island (cagPAI) in 67% of isolates and cagA in 61%, correlating with isolate genetic origin. The most virulent s1m1 vacuolating cytotoxin A genotype was present in 26% of isolates. CONCLUSION: Refractory H. pylori isolates in Australia emanate from multiple global origins. Strong concordance between genetic and phenotypic antibiotic resistance profiles raises the possibility of utilizing genetic profiling in clinical practice. The dynamic landscape of H. pylori in Australia warrants the establishment of a national database to monitor H. pylori resistance and evolving virulence.

Refractory Helicobacter pylori infection in Australia: updated multicentre antimicrobial resistance.

BACKGROUND AND AIM: Helicobacter pylori infection is responsible for considerable morbidity and mortality worldwide and eradication rates are falling globally because of increasing antimicrobial resistance. However, there is a paucity of local data to guide the choice of eradication therapy in Australia. This study aimed to evaluate current Australian rates of H. pylori antibiotic resistance in patients who had failed prior eradication therapy. METHODS: A retrospective analysis of routine culture and antibiotic susceptibility data from two pathology laboratories servicing multiple tertiary referral hospitals in Western Australia (WA) and South Australia (SA), between 2018 and 2022, was performed. Rates of antimicrobial resistance and prevalence of multiresistant isolates in both SA and WA were calculated and comparison of temporal trends and differences between the two states was conducted. RESULTS: A total of 796 H. pylori isolates revealed a clarithromycin resistance rate of 82%, metronidazole 68%, amoxicillin 4.4% and tetracycline 0.5%. Resistance to levofloxacin was observed in 22% and rifampicin 14%. Rates of resistance to clarithromycin were lower in SA compared with WA (incidence rate ratio [IRR]: 0.69, P = 0.0001). Multiresistant isolates were discovered in 63% of patients, with lower rates in SA compared with WA (IRR: 0.74, P = 0.002). CONCLUSION: This first multicentre, multistate study of H. pylori resistance in Australian patients exposed to prior therapy demonstrated high rates of antimicrobial resistance, including levofloxacin (>20%). This raises concern about recommending levofloxacin in empirical second-line therapies. Increased monitoring and awareness of current H. pylori resistance rates in Australia are needed to guide local eradication practices.

Systematic review of therapies for refractory ulcerative proctitis.

Patients with ulcerative proctitis have favorable long-term outcomes but are typically excluded from ulcerative colitis clinical trials. Refractory proctitis presents a management conundrum for gastroenterologists, and there remains a lack of clarity as to the best therapeutic strategy. This study aimed to undertake a systematic review of studies assessing the clinical efficacy and safety of therapies for refractory proctitis. PubMed, Embase, Cochrane Library, and MEDLINE databases were searched without restriction from inception to October 27, 2022. Both interventional and noninterventional studies examining efficacy of therapeutic modalities for the induction and/or maintenance of remission in refractory proctitis were included. Included studies were grouped by therapeutic modalities as follows: (i) immunomodulators, (ii) monoclonal antibodies, (iii) topical calcineurin inhibitors, (iv) other topical therapies, and (v) appendicectomy. The search strategy identified 3301 studies, of which 13 met eligibility criteria for inclusion. Clinical remission rates for systemic therapies ranged from 20-26% for azathioprine to 50-69% for tumor necrosis factor-α inhibitor therapies. The use of systemic therapies for proctitis raised safety concerns, with 22-37% of patients discontinuing therapies due to adverse effects across four retrospective cohort studies. Prospective clinical trials of topically applied tacrolimus demonstrated clinical remission rates of 42-46%, with a favorable safety profile. Substantial heterogeneity in study design precluded meta-analysis. Refractory ulcerative proctitis remains a neglected entity, with a dearth of prospective clinical trials to guide therapeutic decision-making. Current evidence supports a role for topically administered tacrolimus.

Are we underutilising computer tomography colonography in Australia?

Computed tomography colonography (CTC) is a safe and accurate tool for colorectal cancer (CRC) screening in both symptomatic and asymptomatic patients. CTC requires dedicated radiological expertise and demonstrates a high sensitivity and specificity in polyp detection, which is similar to optical colonoscopy (OC). Newer preparation techniques for CTC, such as faecal tagging without catharsis might further improve both the tolerability and accuracy of the test. While exposure to ionising radiation, lack of capacity for therapeutic intervention and potentially diminished sensitivity for flat serrated polyps are limitations of CTC, the technique has a role in select populations. CTC should be considered in frail or elderly patients at high anaesthetic risk for OC, patients with stricturing colonic lesions as well as incomplete colonoscopy, or in patients at risk of delayed access to timely OC. With an ever-growing demand for endoscopic services, increased utilisation of CTC could reduce waiting times for colonoscopy, thereby broadening access to timely and effective CRC screening. Further research is required to improve further the detection of flat lesions, including sessile serrated polyps.

Geospatial analysis of Helicobacter pylori infection in South Australia: Should location influence eradication therapy?

BACKGROUND AND AIM: Rates of antimicrobial-resistant Helicobacter pylori infection are rising globally; however, geospatial location and its interaction with risk factors for infection have not been closely examined. METHODS: Gastric biopsy specimens were collected to detect H. pylori infection at multiple centers in Adelaide, South Australia, between 1998 and 2017. The geospatial distribution of antibiotic-resistant H. pylori in the Greater Adelaide region was plotted using choropleth maps. Moran's I was used to assess geospatial correlation, and multivariate linear regression (MLR) was used to examine associations between migration status, socioeconomic status, age, gender, and rates of H. pylori positivity and antibiotic resistance. Geographically weighted regression (GWR) was used to determine the extent to which the associations varied according to geospatial location. RESULTS: Of 20 108 biopsies across 136 postcodes within the Greater Adelaide region, 1901 (9.45%) were H. pylori positive. Of these, 797 (41.9%) displayed clarithromycin, tetracycline, metronidazole, or amoxicillin resistance. In MLR, migration status was associated with the rate of H. pylori positivity (ß = 3.85% per 10% increase in a postcode's migrant population; P < 0.001). H. pylori positivity and resistance to any antibiotic were geospatially clustered (Moran's I = 0.571 and 0.280, respectively; P < 0.001 for both). In GWR, there was significant geospatial variation in the strength of the migrant association for both H. pylori positivity and antibiotic resistance. CONCLUSION: Our study demonstrates the heterogeneous geospatial distribution of H. pylori positivity and antibiotic resistance, as well as its interaction with migrant status. Geographic location and migrant status are important factors to consider for H. pylori eradication therapy.

Increasing Helicobacter pylori clarithromycin resistance in Australia over 20 years.

BACKGROUND: Helicobacter pylori infection is responsible for considerable morbidity and mortality worldwide, and eradication rates are falling in many countries, primarily due to clarithromycin and metronidazole resistance. AIMS: There is a paucity of contemporary Australian data, which we sought to address by evaluating local rates of resistance of H. pylori to amoxicillin, clarithromycin, metronidazole and tetracycline over the past 20 years. METHODS: All gastric biopsy specimens collected at endoscopy to detect H. pylori infection at a single centre underwent routine culture and antibiotic susceptibility testing between 1998 and 2017. Specimens from 12 842 patients were cultured for H. pylori, of which 1473 positive cultures were tested for antibiotic susceptibility. RESULTS: Antibiotic resistance to clarithromycin increased by 3.7% per year (incidence rate ratio [IRR] 1.037; P = 0.014) over 20 years, with a corresponding 5.0% annual increase in minimum inhibitory concentration (MIC) (odds ratio 1.050; P < 0.001). Since 2010, average clarithromycin resistance has exceeded 20%, with >25% of isolates resistant in the past 2 years of data capture. In contrast, rates of resistance to metronidazole (35.3%), amoxicillin (0.14%) and tetracycline (0.34%) and their MIC have remained stable. Review of a representative sample (n = 120; 8%) of these patients revealed that only 5% had documented prior H. pylori eradication therapy. CONCLUSIONS: Over the past 20 years there has been a substantial rise in clarithromycin resistance, with stable metronidazole resistance and low rates of resistance to amoxicillin and tetracycline. Current first-line H. pylori eradication therapy may fail to achieve adequate eradication rates, and optimal first-line therapy in Australia should be revisited.

Patient-Reported Experience Measures in outpatient rheumatology care: a systematic review.

OBJECTIVES: There is a growing acceptance of the need for routine implementation of patient-reported experience measures (PREMs) in health care. Rheumatology patients, as frequent and long-term users of care, stand to benefit from collection of experience-related data. The aim of this study was to perform a systematic review to identify and critically appraise the development and psychometric validation of PREMs in rheumatology. METHODS: Six databases were searched systematically from inception to 14 December 2020: MEDLINE, EMBASE, PsycINFO, SCOPUS, Cochrane and Google Scholar. We included articles in English that described the use or development of PREMs, with results of psychometric testing, in an adult outpatient rheumatology context. This study is registered with PROSPERO (CRD42021233819). Articles were appraised using the COnsensus Based Standards for the selection of health status Measurement Instruments (COSMIN) (i) Risk of Bias checklist and (ii) criteria for good measurement properties. RESULTS: The search yielded 3809 publications, and six studies met inclusion criteria. All the included studies on PREM development fulfilled COSMIN standards for 'doubtful' or 'inadequate' quality of instrument development. One study fulfilled a 'sufficient' rating for content validity, and the remainder fulfilled 'inconsistent' ratings. During validity testing, studies fulfilled between one and four of the eight COSMIN checklist criteria for good measurement properties. CONCLUSION: Methodological concerns regarding instrument development and validation limit the generalizability of the existing six validated PREMs in use in rheumatology contexts. There is a need for further well-designed studies to validate existing and new PREMs in this area.

Antibiotic resistance of Helicobacter pylori in Australia and New Zealand: A systematic review and meta-analysis.

OBJECTIVE: While the global prevalence of antibiotic-resistant Helicobacter pylori (H. pylori) is increasing, there is much regional variation, and local data are required to guide eradication therapy. We performed a systematic review and meta-analysis to determine rates of H. pylori antibiotic resistance in Australia and New Zealand. STUDY DESIGN: Random effects meta-analysis of data from 15 published studies and three published abstracts reporting prevalence of primary or secondary H. pylori antibiotic resistance in Australasia. DATA SOURCES: PubMed, EMBASE, MEDLINE, PROSPERO, and the Cochrane Library were searched until August, 2020. DATA SYNTHESIS: Fifteen published studies and three published abstracts were identified; one study was excluded due to high risk of bias. Seventeen studies conducted between 1996 and 2013 were included in the final analysis, 12 reporting primary and five reporting secondary antibiotic resistance. Prevalence of primary resistance was clarithromycin 7.4% (95% confidence interval [CI], 5.3-9.7%), metronidazole 50.0% (95%CI, 23.9-56.1%), fluoroquinolones 3.7% (95%CI, 0.004-14.8%), and both amoxicillin and tetracycline <0.5%. Subgroup analysis (last 20 years) showed doubling of clarithromycin resistance to 16.1% (95%CI 11.2-21.7%) with other resistance stable. Prevalence of secondary resistance was high for all antibiotics, particularly clarithromycin 78.7% (95%CI, 64.1-90.1%) and metronidazole 68.3% (95%CI, 59.9-76.1%). CONCLUSIONS: The outcomes reveal an increase in primary H. pylori clarithromycin resistance since the year 2000, while metronidazole resistance has remained stable and primary resistance to amoxicillin, tetracycline, and fluoroquinolones is low. Rates of secondary resistance to metronidazole and clarithromycin are high. The results highlight the need for contemporary local data on antibiotic resistance in Australia and New Zealand.

Effect on Overall Health Status With Weightbearing at 2 Weeks vs 6 Weeks After Open Reduction and Internal Fixation of Ankle Fractures.

BACKGROUND: Ongoing controversy exists on postoperative weightbearing status after open reduction and internal fixation of an ankle fracture. This prospective randomized controlled trial aimed to compare patient-based and physician-based outcomes after early weightbearing at 2 vs 6 weeks postoperatively. METHODS: Fifty patients with unstable rotational-type ankle fractures were treated operatively with subsequent immobilization in a below-the-knee cast for 2 weeks and were then randomly allocated to 2 groups. The first group had early weightbearing at 2 weeks postoperation and the second group at 6 weeks postoperation. Follow-up included subjective and objective evaluations performed at 2, 6, 12, and 26 weeks postoperatively. The primary outcome was the patient-based general health status as measured with the EuroQol-5D (EQ-5D) scoring system. Secondary outcome was the Olerud and Molander ankle score. Power analysis revealed a study group of 50 patients was needed to show a clinically relevant effect size of 10 points in both EQ-5D visual analog scale (VAS) score and Olerud and Molander score. RESULTS: Patients in the early weightbearing group had higher mean EQ-5D VAS scores at a 6-week follow-up (P = .014) of 77 ± 14 compared to 66 ± 15 for late mobilization. No difference was found at other follow-up points or between groups for physician-based outcome measures. At 26 weeks postoperatively, mean Olerud and Molander ankle scores were similar at 84 ± 16 and 81 ± 17 for mobilization at 2 and 6 weeks postoperation, respectively. CONCLUSION: Early weightbearing after operative fixation of rotational-type ankle fractures had a clinically relevant and statistically significant benefit in patient-based general health status, as quantified with EQ-5D VAS scores, at 6 weeks postoperation. These results contribute to our understanding of early weightbearing and may encourage consideration of weightbearing at 2 weeks postoperatively in standard protocols. LEVEL OF EVIDENCE: Therapeutic Level I, prospective randomized controlled trial.

Prevalence and nature of lung function abnormalities among Indigenous Australians referred to specialist respiratory outreach clinics in the Northern Territory.

BACKGROUND: Poor lung function is a predictor of future all-cause mortality. In Australia, respiratory diseases are particularly prevalent among the indigenous population, especially in remote communities. However, there are little published pulmonary function tests' (PFT) data of remote-based adult indigenous patients. AIM: To evaluate the severity of airflow obstruction and other PFT abnormalities of adults referred to specialist respiratory clinics in remote indigenous communities. METHODS: Retrospective analysis of PFT (pre- and post-bronchodilator spirometry, total lung capacity (TLC) and diffusing capacity to carbon monoxide (DLCO)) of indigenous patients collected during specialist respiratory clinics in remote Northern Territory (NT) indigenous communities (Australia) between 2013 and 2015. The National Health and Nutrition Examination Survey (NHANES) III without ethnic correction was used as the reference. RESULTS: Of the 357 patients, 150 had acceptable spirometry, and 71 had acceptable DLCO and TLC studies. Despite the relatively young age (mean = 49 years, SD = 12.9), their lung function was generally low; mean % predicted values were FEV1 = 55% (SD = 20.5%), FVC = 61% (SD = 15.6%), DLCO = 64.0% (SD = 19.7%) and TLC = 70.1% (SD = 18.2%). Mean FEV1 /FVC ratio was preserved (0.71, SD = 0.16). Post-bronchodilator airflow obstruction (FEV1 /FVC < 0.7) was observed in 37% of patients, where a large proportion (67%) demonstrated at least a severe airflow obstruction, with a mean FEV1 of 41% predicted. CONCLUSION: In this first study of PFT findings of indigenous adults from a remote-based clinical service, we found a high rate of at least moderate airflow limitation and low FVC along with preserved FEV1/FVC ratio. Increased awareness and screening for reduced lung function needs to be considered in this population.