Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Canal cholesteatoma in canal stenosis: a case report

Introduction: We present the a-12-year old female with canal stenosis and canal cholesteatoma. We discuss the clinical, radiological and treatment option for canal cholesteatoma in canal stenosis Discussion: Congenital canal atresia is a failure of the development of the external auditory canal which comprises anomalies of variable severity involving pinna, external acoustic canal, middle ear structures and rarely inner ear leading to hearing impairment. Congenital canal stenosis is considered to be a subset of congenital canal atresia. This malformation results in mild to severe conductive hearing loss. Furthermore, the risk of cholesteatoma increased when it is associated with the stenotic ear. Radiological evaluation in the form of an HRCT scan of temporal bones should always be done in these patients during their initial presentation and surgery should be planned accordingly. Their presence should be rule out prior to any corrective surgery. Conclusion: Although the incidence of canal cholesteatoma is rare in congenital canal stenosis, all patients presenting with canal atresia or stenosis should be evaluated thoroughly due to their potential to develop cholesteatoma as it may be challenging to treat at an advanced stage in view of morbid complications.&nbsp

Mastoid surgery outcomes in two tertiary Malaysian hospitals

Objective: Mastoidectomy is a surgical procedure of exenterating the mastoid air cell. The goal of this surgery is to create a dry, safe ear, to preserve or restore functional hearing as much as possible and to prevent complications. There are two types of mastoidectomy, each with their own indications, advantages, and disadvantages. It can be divided into canal wall up mastoidectomy (CWUM) and canal wall down mastoidectomy (CWDM). The objective of this study is to determine the outcome of both types of mastoidectomy in term of audiological and ear status for patients with chronic active otitis media (OM) with cholesteatoma, chronic mastoiditis or chronic active OM with cholesteatoma and mastoiditis managed at our tertiary centres; Universiti Kebangsaan Malaysia Medical Centre (UKMMC) and Kuala Lumpur General Hospital (KLGH). Design: A retrospective 10-year study was conducted at UKMMC and KLGH. Materials & Methods: All patients who were diagnosed with CSOM with / without cholesteatoma and/ or chronic mastoiditis and underwent surgical intervention during the study periods were included in this study. The age, gender, presenting symptoms, complications, diagnosis, surgical procedures and the surgical findings were retrieved from clinical notes. The postoperative pure tone audiometric (PTA) thresholds were evaluated on the follow-up visit within six months to one year after surgery. Results: There were 253 patients recruited with 260 ears as study samples. 103 cases underwent CWUM and 157 cases underwent CWDM. At surgery, cholesteatoma was detected in 68% of the patients. We found 58.3% of ears in the CWUM group showed improvement in hearing threshold whereas only 44.6% showed improvement in the CWDM group. Post-operatively, mean PTA in CWUM (49.7dB) is significantly better than CWDM (59.2dB) with p value of 0.003. In CWUM, the mean air bone gap (ABG) is 24.05dB, which is significantly better than in CWDM (31.03dB). From all patients who underwent CWUM, 42% had post-operative ABG less than 20dB and this only occurred in 20.6% of the CWDM group. For ear status, 85% of patients who underwent CWUM had a dry ear postoperatively, which is significant compared to CWDM which was 69%. Conclusion: CWUM provides a better hearing outcome based on average air conduction (AC) threshold, AC gain and mean ABG. It also has a higher chance of obtaining a safe, dry ear

Main structural targets for engineering lipase substrate specificity

Microbial lipases represent one of the most important groups of biotechnological biocatalysts. However, the high-level production of lipases requires an understanding of the molecular mechanisms of gene expression, folding, and secretion processes. Stable, selective, and productive lipase is essential for modern chemical industries, as most lipases cannot work in different process conditions. However, the screening and isolation of a new lipase with desired and specific properties would be time consuming, and costly, so researchers typically modify an available lipase with a certain potential for minimizing cost. Improving enzyme properties is associated with altering the enzymatic structure by changing one or several amino acids in the protein sequence. This review detailed the main sources, classification, structural properties, and mutagenic approaches, such as rational design (site direct mutagenesis, iterative saturation mutagenesis) and direct evolution (error prone PCR, DNA shuffling), for achieving modification goals. Here, both techniques were reviewed, with different results for lipase engineering, with a particular focus on improving or changing lipase specificity. Changing the amino acid sequences of the binding pocket or lid region of the lipase led to remarkable enzyme substrate specificity and enantioselectivity improvement. Site-directed mutagenesis is one of the appropriate methods to alter the enzyme sequence, as compared to random mutagenesis, such as error-prone PCR. This contribution has summarized and evaluated several experimental studies on modifying the substrate specificity of lipases

Altering the Regioselectivity of T1 Lipase from <i>Geobacillus zalihae</i> toward <i>sn</i>-3 Acylglycerol Using a Rational Design Approach

The regioselectivity characteristic of lipases facilitate a wide range of novel molecule unit constructions and fat modifications. Lipases can be categorized as sn-1,3, sn-2, and random regiospecific. Geobacillus zalihae T1 lipase catalyzes the hydrolysis of the sn-1,3 acylglycerol chain. The T1 lipase structural analysis shows that the oxyanion hole F16 and its lid domain undergo structural rearrangement upon activation. Site-directed mutagenesis was performed by substituting the lid domain residues (F180G and F181S) and the oxyanion hole residue (F16W) in order to study their effects on the structural changes and regioselectivity. The novel lipase mutant 3M switches the regioselectivity from sn-1,3 to only sn-3. The mutant 3M shifts the optimum pH to 10, alters selectivity toward p-nitrophenyl ester selectivity to C14-C18, and maintains a similar catalytic efficiency of 518.4 × 10−6 (s−1/mM). The secondary structure of 3M lipase comprises 15.8% and 26.3% of the α-helix and β-sheet, respectively, with a predicted melting temperature (Tm) value of 67.8 °C. The in silico analysis was conducted to reveal the structural changes caused by the F180G/F181S/F16W mutations in blocking the binding of the sn-1 acylglycerol chain and orientating the substrate to bond to the sn-3 acylglycerol, which resulted in switching the T1 lipase regioselectivity

Prevalence of tinnitus in type II diabetes mellitus with or without hypertension patients in Universiti Kebangsaan Malaysia Medical Centre

Objective: Tinnitus is perception of sound without external stimulus. Our main objective is to determine the prevalence of tinnitus in Type II diabetes mellitus patients with or without hypertension in Universiti Kebangsaan Malaysia Medical Centre. We would also evaluate the quality of life of these patients. The association between tinnitus and glycaemic control and the association with renal function were also looked into. Design: A cross sectional study was conducted from May to July 2015 among 186 respondents with type II diabetes mellitus with or without hypertension using random sampling from the Endocrine clinic, Universiti Kebangsaan Malaysia Medical Centre (UKMMC) Materials and Methods: The respondents were assessed using Tinnitus Handicap Inventory (THI) and laboratory results including HbA1c and renal function were used. Those patients with tinnitus also had pure tone audiometry test to determine the hearing levels. Results: Respondents consisted of 75 males (40.3%) and 111 females (59.7%) with mean age of 60.99 ± 11.6 years old. The racial distribution was 104 Malay (55.9%), 52 Chinese (28.0%), 27 Indian (14.5%) and 3 others (1.6%). The prevalence of patients with tinnitus was 9.1% (17 patients). There was no significant association observed between tinnitus and glycaemic control (p = 0.850) and the severity of renal function calculated from glomerular filtration rate (p = 0.253). Among 17 patients with tinnitus, 10 (58.82%) had grade 1 tinnitus severity, 5 (29.41%) had grade 2 and only 2 (11.76%) had grade 4 tinnitus severity. Conclusion: There was a small percentage of tinnitus in patient with background diabetes. There was no significant association between tinnitus and type II diabetes mellitus or severity of renal function. Tinnitus did not cause a negative impact in the majority of patients