GENES CONFERRING ANTIMICROBIAL-RESISTANCE AMONG KLEBSIELLA PNEUMONIAE IN THE ARABIAN GULF COUNTRIES: A SYSTEMATIC REVIEW AND META-ANALYSIS

Objective: The objective of the study was to look on the prevalence of six AMR genes (CTX-M, TEM, SHV, NDM-1, OXA-48, and VIM genes) in the province of the Arabian Gulf. We performed a systematic review and meta-analysis of the published studies from the Arabian Gulf countries and analyzed the antimicrobial resistance (AMR) genes pattern present in Klebsiella pneumoniae. Methods: The present study used the Meta-analysis Of Observational Studies in Epidemiology as a guideline for reporting findings. An electronic search was conducted in online databases such as PubMed/MEDLINE, EMBASE, Scopus, Google Scholar, Science Direct, and Web of Science from January 2014 to June 2020 following the inclusion and exclusion criteria. Articles published were included in the study resistance pattern among 2036 isolates were analyzed. These isolates conferred the AMR genes including OXA-48 (n=500), CTX-M (n= 1796), SHV (n=1637), TEM (n=1492), NDM-1 (n=500), and VIM (n=302). Results: Of 160 initially searched studies, 28 entries met the inclusion criteria and were subjected to meta-analysis. Critical appraisal of studies or quality assessment revealed a mean quality score was 4.2, with an SD of 1.6. The analysis revealed predominant AMR genes wereOXA-48 followed by CTX-M, SHV, TEM, NDM-1, and VIM in the Arabian Gulf region. Conclusion: The Arabian Gulf countries share a high prevalence of OXA-48, CTX-M followed by SHV, TEM, NDM-1, and VIM genes. Antimicrobial-resistant in K. pneumoniae is a threat to public health and this needs strong surveillance to curb this threat

Characterization of cephalosporin-resistant clinical Enterobacteriaceae for CTX-M ESBLs in Bahrain

AbstractObjectiveTo detect the presence of specific CTX-M class of extended spectyum β-lactamases (ESBLs) in a collection of cephalosporin-resistant Enterobacteriaceae isolates from Bahrain.MethodsA subset of 80 cephalosporin-resistant Enterobacteriaceae collected from Salmaniya Medical Complex, Bahrain, were characterized further for the presence of specific genogroups of CTX-M β-lactamases by multiplex- and monoplex- PCRs. The primers used for the multiplex and monoplex PCRs were of genogroups- 1, 2, 8, 9 and 25. Sequencing of the representative isolates was performed to find the circulating CTX-M-types.ResultsA total of 93.8% (75/80) isolates showed the amplicons corresponding to any of the genogroups (1, 2, 8, 9, 25) and the remaining 6.2% isolates turned out negative in multiplex PCR. Some of the isolates demonstrated multiple bands corresponding to the sizes of different genogroups. Further confirmation with respective monoplex PCR on these 75 isolates demonstrated that 93.3% (70/75) harbored CTX-M genogroup-1 and 6.7% (5/75) harbored genogroup-9. We did not find the presence of genogroups 2, 8, and 25 in these isolates by monoplex PCR. Sequencing results of genogroup-1 isolates demonstrated the presence of CTX-M-15-like ESBL, however, discrepant results were noticed in genogroup-9 isolates, sequencing showed them as CTX-M-55-like ESBL.ConclusionsThis is the first report from Bahrain characterizing the CTX-M genogroups of ESBLs and reporting the emergence of blaCTX-M-55-like gene in this region

Exploring the evidence base for national and regional policy interventions to combat resistance

The effectiveness of existing policies to control antimicrobial resistance is not yet fully understood. A strengthened evidence base is needed to inform effective policy interventions across countries with different income levels and the human health and animal sectors. We examine three policy domains—responsible use, surveillance, and infection prevention and control—and consider which will be the most effective at national and regional levels. Many complexities exist in the implementation of such policies across sectors and in varying political and regulatory environments. Therefore, we make recommendations for policy action, calling for comprehensive policy assessments, using standardised frameworks, of cost-effectiveness and generalisability. Such assessments are especially important in low-income and middle-income countries, and in the animal and environmental sectors. We also advocate a One Health approach that will enable the development of sensitive policies, accommodating the needs of each sector involved, and addressing concerns of specific countries and regions

Reported Adverse Effects and Attitudes among Arab Populations Following COVID-19 Vaccination: A Large-Scale Multinational Study Implementing Machine Learning Tools in Predicting Post-Vaccination Adverse Effects Based on Predisposing Factors

Background: The unprecedented global spread of coronavirus disease 2019 (COVID-19) has imposed huge challenges on the healthcare facilities, and impacted every aspect of life. This has led to the development of several vaccines against COVID-19 within one year. This study aimed to assess the attitudes and the side effects among Arab communities after receiving a COVID-19 vaccine and use of machine learning (ML) tools to predict post-vaccination side effects based on predisposing factors. Methods: An online-based multinational survey was carried out via social media platforms from June 14 to 31 August 2021, targeting individuals who received at least one dose of a COVID-19 vaccine from 22 Arab countries. Descriptive statistics, correlation, and chi-square tests were used to analyze the data. Moreover, extensive ML tools were utilized to predict 30 post vaccination adverse effects and their severity based on 15 predisposing factors. The importance of distinct predisposing factors in predicting particular side effects was determined using global feature importance employing gradient boost as AutoML. Results: A total of 10,064 participants from 19 Arab countries were included in this study. Around 56% were female and 59% were aged from 20 to 39 years old. A high rate of vaccine hesitancy (51%) was reported among participants. Almost 88% of the participants were vaccinated with one of three COVID-19 vaccines, including Pfizer BioNTech (52.8%), AstraZeneca (20.7%), and Sinopharm (14.2%). About 72% of participants experienced post-vaccination side effects. This study reports statistically significant associations (p < 0.01) between various predisposing factors and post-vaccinations side effects. In terms of predicting post-vaccination side effects, gradient boost, random forest, and XGBoost outperformed other ML methods. The most important predisposing factors for predicting certain side effects (i.e., tiredness, fever, headache, injection site pain and swelling, myalgia, and sleepiness and laziness) were revealed to be the number of doses, gender, type of vaccine, age, and hesitancy to receive a COVID-19 vaccine. Conclusions: The reported side effects following COVID-19 vaccination among Arab populations are usually non-life-threatening; flu-like symptoms and injection site pain. Certain predisposing factors have greater weight and importance as input data in predicting post-vaccination side effects. Based on the most significant input data, ML can also be used to predict these side effects; people with certain predicted side effects may require additional medical attention, or possibly hospitalization

Non-invasive diagnostic tests for Helicobacter pylori infection

BACKGROUND: Helicobacter pylori (H pylori) infection has been implicated in a number of malignancies and non-malignant conditions including peptic ulcers, non-ulcer dyspepsia, recurrent peptic ulcer bleeding, unexplained iron deficiency anaemia, idiopathic thrombocytopaenia purpura, and colorectal adenomas. The confirmatory diagnosis of H pylori is by endoscopic biopsy, followed by histopathological examination using haemotoxylin and eosin (H & E) stain or special stains such as Giemsa stain and Warthin-Starry stain. Special stains are more accurate than H & E stain. There is significant uncertainty about the diagnostic accuracy of non-invasive tests for diagnosis of H pylori. OBJECTIVES: To compare the diagnostic accuracy of urea breath test, serology, and stool antigen test, used alone or in combination, for diagnosis of H pylori infection in symptomatic and asymptomatic people, so that eradication therapy for H pylori can be started. SEARCH METHODS: We searched MEDLINE, Embase, the Science Citation Index and the National Institute for Health Research Health Technology Assessment Database on 4 March 2016. We screened references in the included studies to identify additional studies. We also conducted citation searches of relevant studies, most recently on 4 December 2016. We did not restrict studies by language or publication status, or whether data were collected prospectively or retrospectively. SELECTION CRITERIA: We included diagnostic accuracy studies that evaluated at least one of the index tests (urea breath test using isotopes such as13C or14C, serology and stool antigen test) against the reference standard (histopathological examination using H & E stain, special stains or immunohistochemical stain) in people suspected of having H pylori infection. DATA COLLECTION AND ANALYSIS: Two review authors independently screened the references to identify relevant studies and independently extracted data. We assessed the methodological quality of studies using the QUADAS-2 tool. We performed meta-analysis by using the hierarchical summary receiver operating characteristic (HSROC) model to estimate and compare SROC curves. Where appropriate, we used bivariate or univariate logistic regression models to estimate summary sensitivities and specificities. MAIN RESULTS: We included 101 studies involving 11,003 participants, of which 5839 participants (53.1%) had H pylori infection. The prevalence of H pylori infection in the studies ranged from 15.2% to 94.7%, with a median prevalence of 53.7% (interquartile range 42.0% to 66.5%). Most of the studies (57%) included participants with dyspepsia and 53 studies excluded participants who recently had proton pump inhibitors or antibiotics.There was at least an unclear risk of bias or unclear applicability concern for each study.Of the 101 studies, 15 compared the accuracy of two index tests and two studies compared the accuracy of three index tests. Thirty-four studies (4242 participants) evaluated serology; 29 studies (2988 participants) evaluated stool antigen test; 34 studies (3139 participants) evaluated urea breath test-13C; 21 studies (1810 participants) evaluated urea breath test-14C; and two studies (127 participants) evaluated urea breath test but did not report the isotope used. The thresholds used to define test positivity and the staining techniques used for histopathological examination (reference standard) varied between studies. Due to sparse data for each threshold reported, it was not possible to identify the best threshold for each test.Using data from 99 studies in an indirect test comparison, there was statistical evidence of a difference in diagnostic accuracy between urea breath test-13C, urea breath test-14C, serology and stool antigen test (P = 0.024). The diagnostic odds ratios for urea breath test-13C, urea breath test-14C, serology, and stool antigen test were 153 (95% confidence interval (CI) 73.7 to 316), 105 (95% CI 74.0 to 150), 47.4 (95% CI 25.5 to 88.1) and 45.1 (95% CI 24.2 to 84.1). The sensitivity (95% CI) estimated at a fixed specificity of 0.90 (median from studies across the four tests), was 0.94 (95% CI 0.89 to 0.97) for urea breath test-13C, 0.92 (95% CI 0.89 to 0.94) for urea breath test-14C, 0.84 (95% CI 0.74 to 0.91) for serology, and 0.83 (95% CI 0.73 to 0.90) for stool antigen test. This implies that on average, given a specificity of 0.90 and prevalence of 53.7% (median specificity and prevalence in the studies), out of 1000 people tested for H pylori infection, there will be 46 false positives (people without H pylori infection who will be diagnosed as having H pylori infection). In this hypothetical cohort, urea breath test-13C, urea breath test-14C, serology, and stool antigen test will give 30 (95% CI 15 to 58), 42 (95% CI 30 to 58), 86 (95% CI 50 to 140), and 89 (95% CI 52 to 146) false negatives respectively (people with H pylori infection for whom the diagnosis of H pylori will be missed).Direct comparisons were based on few head-to-head studies. The ratios of diagnostic odds ratios (DORs) were 0.68 (95% CI 0.12 to 3.70; P = 0.56) for urea breath test-13C versus serology (seven studies), and 0.88 (95% CI 0.14 to 5.56; P = 0.84) for urea breath test-13C versus stool antigen test (seven studies). The 95% CIs of these estimates overlap with those of the ratios of DORs from the indirect comparison. Data were limited or unavailable for meta-analysis of other direct comparisons. AUTHORS' CONCLUSIONS: In people without a history of gastrectomy and those who have not recently had antibiotics or proton ,pump inhibitors, urea breath tests had high diagnostic accuracy while serology and stool antigen tests were less accurate for diagnosis of Helicobacter pylori infection.This is based on an indirect test comparison (with potential for bias due to confounding), as evidence from direct comparisons was limited or unavailable. The thresholds used for these tests were highly variable and we were unable to identify specific thresholds that might be useful in clinical practice.We need further comparative studies of high methodological quality to obtain more reliable evidence of relative accuracy between the tests. Such studies should be conducted prospectively in a representative spectrum of participants and clearly reported to ensure low risk of bias. Most importantly, studies should prespecify and clearly report thresholds used, and should avoid inappropriate exclusions

Plasmid Derived AmpC Genotypes among the Multidrug Resistant Enterobacteriaceae Strains Isolated from Urine Samples in Southern India

Introduction: The most common pathogens causing Urinary Tract Infections (UTI) in community and hospital settings are Enterobacteriaceae. Antibiotic resistance is a major problem worldwide because of an increase in the use of antibiotics. Production of Extended Spectrum Beta-Lactamases (ESBLs) and AmpC beta-lactamases is the most common cause of resistance among Enterobacteriaceae (AmpC). Initially, AmpC b-lactamases received less attention globally, but now it has become a rising problem. Detection of AmpC β-lactamases expressing microbes is a requirement for addressing surveillance, for problems of hospital infection control, and for choosing optimal antimicrobial therapy. Aim: To study the genotype distribution of plasmid mediated AmpC β-lactamase produced in Enterobacteriaceae strains isolated from urine samples. Materials and Methods: A cross-sectional study based on clinical laboratory surveillance was conducted from July 2019 to February 2020. Sixty Enterobacteriaceae isolates were identified by standard biochemical reactions. AmpC screening were done by cefoxitin disk diffusion and confirmed by an inhibitor-based assay using boronic acid. The presence of six plasmid mediated AmpC genes was determined by multiplex Polymerase Chain Reaction (PCR). Statistical Package for the Social Science (SPSS) version 20.0 was used to obtain descriptive data. Results: Among 60 Enterobacteriaceae isolates, 23 (38.3%) were cefoxitin-resistant isolates which contain Escherichia coli strain (n=17) while the remaining samples consist of Klebsiella pneumoniae (n=5) and Proteus mirabilis strains (n=1). AmpC β-lactamase production was phenotypically confirmed in 12 (20%) isolates and genotypically confirmed by PCR analysis in 16 (26.6%) of all the urine isolates. In the present study, 3 (13%), 2 (8.6%) of cefoxitin resistant isolates harboured the DHA, EBC gene and 1 (4.3%) each harboured FOX and CIT gene, and 9 (39.1%) harboured a combination of the genes. Conclusion: The present study suggested the predominant existence of plasmid mediated AmpC producers in multi-drug resistant Escherichia coli and Klebsiella pneumoniae. We suggest continuous surveillance is important to effectively control the spread of these strains and for optimal clinical outcome

The Prevalence of Antimicrobial Resistance and Serotypes of Streptococcus pneumoniae in the Kingdom of Bahrain

Streptococcus pneumoniae (S. pneumoniae), also known as pneumococcus, is found in the upper respiratory tract of 5-70% of healthy people. It causes otitis media, pneumonia and invasive pneumococcal diseases (IPD). The group with the highest risk for pneumococcal diseases are children, elderly people and people with chronic systemic illnesses. The identification of these serotypes is crucial to monitor the prevalent serotypes, to track resistance patterns, and to evaluate the efficacy of treatment and vaccination. Our aim was to determine antibiotic resistance in S. pneumoniae, identify the most common serotypes, determine the association between highly resistant strains and most common serotypes, and select an effective vaccine against the predominant serotypes in the Kingdom of Bahrain. One hundred isolates were included in the study. Antimicrobial susceptibility was determined by agar dilution and serotypes were determined by the Quellung reaction. Antimicrobial resistance rates were highest for penicillin in children ≤ 5 years old (34%) and elderly patients (29%). For the serotypes distribution of S. pneumoniae, the predominant serotypes were 19, 6, 23, 3 and 14 in the different age groups. The predominant serotypes that showed resistance to three antimicrobial agents were 19, 6, 23 and 14. The increasing pneumococcal resistance to penicillin, erythromycin, and tetracycline indicates the need for preventive measures, antibiotics use monitoring and stewarding. In light of the expanding prevalence of S. pneumoniae resistant to multiple antimicrobial agents, the need for an effective pneumococcal vaccine has become very important