Search

Khalid Mubarak Bindayna, Ahmed Qareeballa, Ronni Mol Joji, Ali Al Mahmeed, Hicham Ezzat, Abdulrahman Yousif Ismaeel, Khaled S Tabbara Microbiology, Immunology and Infectious Diseases Department, College of Medicine and Medical Sciences, Arabian Gulf University, Manama, Kingdom of BahrainCorrespondence: Khalid Mubarak Bindayna Microbiology, Immunology, and Infectious Diseases Department, College of Medicine and Medical SciencesArabian Gulf University, Manama, Kingdom of BahrainEmail bindayna@agu.edu.bhIntroduction: The curriculum at medical school at Arabian Gulf University is centered on small group learning and real-life problems provided to students and guiding students to learn actively. In microbiology, laboratory skills are taught in an innovative manner using mini cases and different lab sessions and are integrated with other basic sciences. This article describes the format and pattern of laboratory skills sessions conducted using PBL methods at Arabian Gulf University and discusses the perception of students towards PBL in laboratory skill learning and way forward for the same.Methods: The study sample size was 110. The students’ perception of the laboratory skills teaching methods was assessed through an exit survey at the end of each session. A semi-structured self-administered survey instrument was prepared, and the questions were arranged in two sessions and focused on identifying the relevance, timing, strengths, and weaknesses of the teaching method and recommendations to improve the same.Results: We observed that more than 50% of the participants agreed or strongly agreed that the time given for PBL was adequate, topics discussed were relevant, presentations were clear, pre-session briefing and Case-Based Studies (team-based learning (TBL)) helped in their learning. The participants identified the demonstration of experiments and hands-on experience provided in the laboratory were most helpful. When enquired about the difficulty, among 48% of the participants, 80% observed that the slides used in the learning/teaching were lengthy.Conclusion: The use of PBL in a lab setting promotes active learning. In the heart of PBL, TBL is a powerful tool in the educational process offering the students deep comprehension and allowing them to gain practical and intellectual skills.Keywords: PBL, microbiology, laboratory skill learning more...

Background: Acinetobacter baumannii is a serious health concern worldwide, causing high mortality rates and limited medical therapy options. Carbapenem resistance is a significant problem in Acinetobacter baumannii isolates. The synthesis of acquired carbapenemases, such as oxacillinases, IMP, NDM, VIM, and KPC enzymes, causes carbapenem resistance., Methods: A total of 106 non-repetitive, Acinetobacter baumannii isolates were collected from four major hospitals in Bahrain including 78 carbapenem-resistant Acinetobacter baumannii (CRAB), and 28 carbapenem-susceptible Acinetobacter baumannii (CSAB) isolates. Three phenotypic tests were investigated in this study: including CARBA NP, modified carbapenem inactivation method (mCIM)/EDTA-CIM (eCIM), and modified Hodge test (MHT)., Results: CARBA NP was positive in 50 tested CRAB isolates (100%), and the sensitivity was 100%. The MHT was positive in 73/106 isolates (68.8%), while the sensitivity and specificity of the MHT were 77.6% and 100%. Moreover, only 38/106 (35.8%) isolates were positive for mCIM/eCIM. The sensitivity and specificity of mCIM were 40.4% and 100%., Conclusion: CARBA NP was ideal for phenotypic detection of carbapenemase production, followed by MHT. The m/eCIM demonstrated a lower detection rate in CRAB. Consequently, combining tests would be more accurate. The mCIM/eCIM can easily distinguish between MBLs and serine-carbapenemases due to the frequent co-production of these enzymes in A. baumannii. In hospital setups where molecular characterization tests are not available, CARBA NP seems to be an alternative test in combination with MHT or mCIM/eCIM., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Indian Association of Medical Microbiologists. Published by Elsevier B.V. All rights reserved.) more...

The emergence of extended-spectrum β-lactamase-producing Klebsiella pneumoniae , including CRKP infections, has resulted in significant morbidity and mortality worldwide. We aimed to explore the presence of bla genes (CTX-M, TEM, and SHV) in CRKP isolates. A total of 24 CRKP isolates were randomly selected from the Salmaniya Medical Complex Microbiology Laboratory. These isolates, which were positive for carbapenemases, were further explored for CTX-M, TEM, and SHV genes using PCR. All the CTX-M PCR amplicons were sent for sequencing. To determine genetic relatedness, molecular typing by ERIC-PCR was performed. The bla gene testing demonstrated that a significant proportion of these isolates harbored SHV, CTX-M, and TEM genes (100%, 91.6%, and 45.8%), respectively. Bioinformatic analyses confirmed CTX-M-15 in these isolates. ERIC-PCR analysis showed three clusters demonstrating genetic relatedness. The study findings reveal the concomitant carriage of the SHV and CTX-M-15 and a comparatively lower carriage of TEM genes in CRKP isolates. Our findings highlight the significance of routinely reporting the presence of antibiotic resistance genes along with regular antibiotic sensitivity reports, as this will aid clinicians in prescribing appropriate antibiotics. more...

Background Panton-Valentine leukocidin (PVL) is one of the most important determinants of virulence in Staphylococcus aureus. It is associated with a propensity for complicating skin and soft tissue infections and necrotizing pneumonia. This study aims to quantitively examine the effect of ascorbic acid and nicotinamide on PVL production in the reference strain USA300. Methodology Sandwich enzyme-linked immunosorbent assay (ELISA) was used to quantitively measure the production of PVL via the commercial LukS sandwich ELISA kit (IBT Bio-services, MD, USA). Results Incubating USA300 with subinhibitory concentrations of antioxidants resulted in a statistically significant eight-fold reduction in PVL production at 1.25 mg/mL and 30 mg/mL for ascorbic acid and nicotinamide, respectively. Although the mechanism by which antioxidants inhibit PVL production is yet to be elucidated, we suggest that it can be due to interrupting PVL gene expression. Conclusions Ascorbic acid and nicotinamide have the potential to be toxin-suppressing agents that may be effective in supporting the bactericidal effect of antibiotics to improve the outcome of PVL-associated infections; however, further extensive research is required., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, AlSaleh et al.) more...

Background: Acinetobacter baumannii is regarded as a significant cause of death in hospitals. The WHO recently added carbapenem-resistant Acinetobacter baumannii (CRAB) to its global pathogen priority list. There is a dearth of information on CRAB from our region., Methods: Fifty CRAB isolates were collected from four main hospitals in Bahrain for this study. Bacterial identification and antibiotic susceptibility tests were carried out using the BD Phoenix TM and VITEK-2 compact, respectively. Using conventional PCR, these isolates were further screened for carbapenem resistance markers ( bla OXA-51 , bla OXA-23 , blaO XA-24 , bla OXA-40 , bla IMP , bla NDM , bla VIM , and bla KPC )., Results: All of the isolates were resistant to imipenem (100%), meropenem (98%), and cephalosporins (96-98%), followed by other commonly used antibiotics. All these isolates were least resistant to gentamicin (64%). The detection of resistance determinants showed that the majority harbored bla OXA-51 (100%) and bla IMP (94%), followed by bla OXA-23 (82%), bla OXA-24 (46%), bla OXA-40 (14%), bla NDM (6%), bla VIM (2%), and bla KPC (2%)., Conclusion: The study isolates showed a high level of antibiotic resistance. Class D carbapenemases were more prevalent in our CRAB isolate collection. The resistance genes were found in various combinations. This study emphasizes the importance of strengthening surveillance and stringent infection control measures in clinical settings to prevent the emergence and further spread of such isolates. more...

Background: Methicillin-resistant Staphylococcus aureus (MRSA) is a ubiquitous pathogen associated with a wide spectrum of human infections. In recent decades, MRSA infections have been increasingly reported in individuals without established risk factors, infecting immunocompetent members of the community. This emergence is attributed to the production of various virulence factors, notably Panton-Valentine leukocidin (PVL)., Objective: The aim of this study was to better understand the prevalence, antibiotic resistance profiles, and molecular characteristics of S. aureus and MRSA in a tertiary care hospital in the Kingdom of Bahrain., Materials and Methods: This cross-sectional study was carried out in a tertiary hospital for a one-year period, from December 2020 to December 2021. A total of 161 consecutive S. aureus isolates were collected. Antibiotic susceptibility was tested using BD Phoenix™ automated identification and susceptibility testing system. Molecular analysis was conducted via conventional PCR and conventional multiplex PCR for SCC mec typing., Results: In this study, 161 S. aureus isolates were investigated, 60% (n=97) were characterized as MRSA, of which, 12% (n=12) were healthcare-associated methicillin-resistant Staphylococcus aureus (HA-MRSA) while 88% (n=85) were community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA). No statistically significant difference (P>0.05) in antibiotic resistance trends between HA-MRSA and CA-MRSA was detected. Multidrug resistance (MDR) amounted to 19% (n=30) of all S. aureus isolates, 14% (n=9) of methicillin-susceptible Staphylococcus aureus (MSSA) isolates, and 22% (n=21) of MRSA isolates. SCC mec typing demonstrated a high prevalence of type IV (61%, n=59), followed by type V (32%, n=31), then type II (4%, n=4), and type III (3%, n=3). The PVL prevalence was 39% (n=25) in MSSA and 62% (n=60) in MRSA, 33% (n=4) in HA-MRSA, and 66% (n=56) in CA-MRSA., Conclusion: This study demonstrated the emergence of PVL-producing CA-MRSA in a tertiary care hospital, as well as the detection of PVL-producing MDR strains. This development prompts serious measures to be taken in order to sustain a healthy clinical environment., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, AlSaleh et al.) more...

The prevalence of Carbapenem-resistant Klebsiella pneumoniae (CRKP) is currently increasing worldwide, prompting WHO to classify it as an urgent public health threat. CRKP is considered a difficult to treat organism owing to limited therapeutic options. In this study, a total of 24 CRKP clinical isolates were randomly collected from Salmaniya Medical Complex, Bahrain. Bacterial identification and antibiotic susceptibility testing were performed, on MALDI-TOF and VITEK-2 compact, respectively. The isolates were screened for carbapenem resistance markers ( bla NDM, bla OXA-23, bla OXA-48 and bla OXA-51 ) and plasmid-mediated quinolone resistance genes ( qnrA, qnrB , and qnrS ) by monoplex PCR. On the other hand, only colistin-resistant isolates (n=12) were screened for MCR-1, MCR-2 and MCR-3 genes by monoplex PCR. Moreover, the Genetic environment of bla NDM , integrons analysis, and molecular characterization of plasmids was also performed. Antibiotic susceptibility revealed that all the isolates (100%) were resistant to ceftolozane/tazobactam, piperacillin/tazobactam, 96% resistant to ceftazidime, trimethoprim/sulfamethoxazole, 92% resistant to meropenem, gentamicin and cefepime, 88% resistant to ciprofloxacin, imipenem, and 37% resistant to amikacin. Ceftazidime/avibactam showed the least resistance (12%). 75% (n=12/16) were resistant to colistin and 44% (n=7/16) showed intermediate susceptibility to tigecycline. The detection of resistant determinants showed that the majority (95.8%) of CRKP harbored bla NDM-1 , followed by bla OXA-48 (91.6%) bla OXA-51 (45.8%), and bla OXA-23 (41.6%). Sequencing of the bla NDM amplicons revealed the presence of bla NDM-1 . Alarmingly, 100% of isolates showed the presence of qnrS . These predominant genes were distributed in various combinations wherein the majority were bla NDM-1 + bla OXA-51 + qnrS + bla OXA-48 (n =10, 41.7%), bla NDM-1 + bla OXA-23 + qnrS + bla OXA-48 (n=8, 33.3%), among others. In conclusion, the resistance rate to most antibiotics is very high in our region, including colistin and tigecycline, and the genetic environment of CRKP is complex with the carriage of multiple resistance markers. Resistance to ceftazidime/avibactam is uncommon and hence can be used as a valuable option for empirical therapy. Molecular data on resistance markers and the genetic environment of CRKP is lacking from this geographical region; this would be the first report addressing the subject matter. Surveillance and strict infection control strategies should be reinforced in clinical settings to curb the emergence and spread of such isolates., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Shahid, Ahmad, Saeed, Shadab, Joji, Al-Mahmeed, Bindayna, Tabbara and Dar.) more...

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 14 June 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. more...

Background: Antimicrobial resistance (AMR) in Escherichia coli is an alarming issue worldwide, including in the Gulf Cooperation Council (GCC) countries, yet the prevailing gene patterns have not recently been reviewed. This study was conducted to determine and report on the dominant E. coli antimicrobial resistant gene patterns in GCC countries., Method: A scoping review identified the predominant AMR genes in GCC countries: CTX M, TEM, SHV, NDM, OXA, and VIM genes. For the systematic review, two authors independently searched Scopus, PubMed, Google Scholar, Science Direct, and Web of Science for interventional, clinical, or observational studies on the chosen AMR-conferring genes in E. coli published from GCC countries between January 2013 and June 2019, when the last search was carried out. The search strategy followed the PRISMA guidelines. The risk of bias was assessed using a 6-item standardized checklist. Random-effects modeling was used for all analyses., Results: A total 32 studies were included in the final synthesis of evidence. Overall, CTX-M (53.8%) was the most prevalent gene in the region followed TEM (40.6%), NDM-1 (28.4%), OXA (24.3%), VIM (8.5%), and SHV (7.8%). Most included studies were from Saudi Arabia: CTX-M was again most common with a prevalence of 46.8% from 5442 isolates., Conclusion: The risk of bias analysis showed a mean quality score of 4.25 ± 0.75, indicating high-quality in studies included in this meta-analysis. This review found that CTX-M gene is the most common AMR-conferring gene in E. coli strains from most GCC countries., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Saudi Journal of Medicine & Medical Sciences.) more...

Objectives: Sepsis is a serious medical condition caused by the body's systemic inflammatory response to infections. The antimicrobial peptides, human beta-defensins, play a key role in modulating host immune responses, and aberrant expression of human beta-defensins has been implicated in many infections and inflammatory diseases. However, little is known about the expression of human beta-defensin-3 in systemic infectious diseases., Methods: We investigated the gene expression and protein level of human beta-defensin-3 in peripheral whole blood from 107 participants-67 patients with sepsis and 40 healthy controls-and evaluated the feasibility of human beta-defensin-3 as an indicator for sepsis. Total RNA was extracted from peripheral blood samples, and relative mRNA expression of human beta-defensin-3 was determined by reverse transcription-quantitative polymerase chain reaction. Plasma concentration of human beta-defensin-3 was measured by enzyme-linked immunosorbent assay. Pearson's correlation analysis was performed to assess the relationship between human beta-defensin-3 mRNA and protein levels. Receiver operating characteristic analysis was performed to evaluate the value of human beta-defensin-3 as a biomarker for sepsis., Results: Human beta-defensin-3 mRNA expression was significantly downregulated in sepsis patients compared to controls (p = 0.001). The mean fold change of mRNA expression (±standard error) was 0.82 ± 0.63 in sepsis patients and 1.39 ± 1.09 in controls. Plasma concentration of human beta-defensin-3 (pg/mL) was significantly lower in sepsis patients compared to healthy controls (p = 0.039). The mean protein concentration (±standard error) was 539.6 ± 39.4 in sepsis patients and 715.5 ± 53 in controls. There was a significant correlation between human beta-defensin-3 mRNA expression and the corresponding protein level in sepsis patients (r = 0.358, p = 0.04), but not in healthy controls (r = 0.124, p = 0.51). For discriminating sepsis patients from healthy controls, the area under the receiver operating characteristic curve was 0.722 (95% confidence interval: 0.597-0.847, p = 0.002) for human beta-defensin-3 mRNA and 0.689 (95% confidence interval: 0.557-0.827, p = 0.009) for human beta-defensin-3 protein., Conclusion: This is the first study to show the downregulation of human beta-defensin-3 gene expression and protein level in sepsis, which may contribute to the complex immunological imbalance in sepsis. The significant correlation between human beta-defensin-3 mRNA expression and protein concentration suggests that mRNA expression could be used to predict protein level. Our study also showed a potential role of human beta-defensin-3 as a blood-based biomarker for sepsis. More studies on the clinical significance of human beta-defensin-3 in sepsis could further support a biomarker development., Competing Interests: Declaration of conflicting interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2021.) more...

The challenges imposed by the ongoing outbreak of severe acute respiratory syndrome coronavirus-2 affects every aspect of our modern world, ranging from our health to our socio-economic needs. Our existence highly depends on the vaccine's availability, which demands in-depth research of the available strains and their mutations. In this work, we have analyzed all the available SARS-COV2 genomes isolated from the Kingdom of Bahrain in terms of their variance and origin analysis. We have predicted various known and unique mutations in the SARS-COV2 isolated from Bahrain. The complexity of the phylogenetic tree and dot plot representation of the strains mentioned above with other isolates of Asia indicates the versatility and multiple origins of Bahrain's SARS-COV2 isolates. We have also identified two high impact spike mutations from these strains which increase the virulence of SARS-COV2. Our research could have a high impact on vaccine development and distinguishes the source of SARS-COV2 in the Kingdom of Bahrain., (Copyright © 2021. Published by Elsevier Ltd.) more...

Background: Enterobacteriaceae with AmpC β-lactamase are multidrug-resistant organisms and represent a significant challenge to patient care. This study aims to determine the prevalence of plasmid-derived AmpC β-lactamase among extended spectrum β-lactamases (ESBL)-producing Enterobacteriaceae strains in Bahrain., Methods: It was a cross-sectional study. A total of 185 ESBL-producing Enterobacteriaceae isolates were recovered from clinically significant specimens from January 2018 to December 2019. The samples underwent initial screen for cefoxitin resistance by disc diffusion test and subsequent phenotypic confirmation of AmpC production with phenyl boronic acid assays as well as genotypic analysis by multiplex polymerase chain reactions for AmpC subtypes. Drug-resistant features of these clinical isolates were also examined., Results: Twenty-nine ESBL-producing Enterobacteriaceae isolates were cefoxitin resistant. Phenotypic and genotypic analyses confirmed that 8 and 12 cefoxitin-resistant isolates are AmpC positive, respectively. These AmpC producers are multidrug resistant, and Escherichia coli is the dominant strain among them., Conclusions: Plasmid-mediated spread of AmpC is present in clinically relevant Enterobacteriaceae species in Bahrain. Rational antimicrobial therapy against these multidrug-resistant organisms and continued surveillance of antimicrobial resistance mechanisms among the clinical isolates are recommended for optimal patient care., Competing Interests: There are no conflicts of interest., (Copyright: © 2021 Annals of Thoracic Medicine.) more...

Objectives  AmpC β-lactamases are cephalosporinases that confer resistance to cephalothin, cefazolin, cefoxitin, penicillin, and β-lactamase inhibitor-β-lactam combinations. Even though the AmpC resistance is reported, but the accurate occurrence of AmpC β-lactamases in Enterobacteriaceae members is still unknown. Techniques to identify AmpC producers are still evolving but not yet optimized for the clinical laboratory. Here we aimed to compare the test performance of two different phenotypic methods, that is inhibitor-based assay using boronic acid and disk approximation test for AmpC detection in Enterobacteriaceae isolates from a tertiary hospital microbiology laboratory. Materials and Methods  The study includes 137 nonrepeat Enterobacteriaceae strains. Bacterial isolates, that yielded a zone diameter of less than 18 mm for cefoxitin by disk diffusion method were considered potential AmpC producers and further confirmed by phenotype methods-inhibitor-based assay using boronic acid and disk approximation test. A multiplex polymerase chain reaction was used to detect the most common plasmid-mediated AmpC genes: ACC, FOX, MOX, DHA, CIT, and EBC. Results  Of the 137 clinical isolates, 58 (42.33%) were cefoxitin resistant, while 53.4 and 18.9% of the cefoxitin-resistant isolates were positive by inhibitor-based assay and disk approximation test. Multiplex PCR detected 42 (30.6%) isolates with AmpC genes. Of the 42 isolates, the inhibitor-based assay detected 25 (59.5%) isolates, while the disk approximation test detected nine (21.4%) isolates. Conclusion  Our findings suggest that inhibitor-based assay using boronic acid can be used for the detection of the isolates that harbor AmpC β-lactamases. This method is cost-effective, simple to perform, and easy to interpret. Thus AmpC detection as a routine in clinical laboratories can help in appropriate therapeutic intervention and improved infection control., Competing Interests: Conflict of InterestEthical ApprovalAuthors’ ContributionFinancial Disclosure None declared. This research is approved by Annamalai Institutional Review Board. R.M.P. contributed towards concept, design, literature search, experimental studies, data acquisition, data analysis, statistical analysis, and manuscript preparation. G.S. did the data analysis, manuscript editing, and manuscript review. K.M.B. contributed towards data analysis, manuscript editing, and manuscript review. None., (The Indian Association of Laboratory Physicians. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).) more...

Background: Coronavirus (COVID-19) was introduced into society in late 2019 and has now reached over 88 million cases and 1.9 million deaths. The Middle East has a death toll of ~80,000 and over 35000 of these are in Iran, which has over 1.2 million confirmed cases. We expect that Iranian cases caused outbreaks in the neighbouring countries and that variant mapping and phylogenetic analysis can be used to prove this. We also aim to analyse the variants of severe acute respiratory syndrome coronavirus-2 (SARS -CoV-2) to characterise the common genome variants and provide useful data in the global effort to prevent further spread of COVID-19., Methods: The approach uses bioinformatics approaches including multiple sequence alignment, variant calling and annotation and phylogenetic analysis to identify the genomic variants found in the region. The approach uses 122 samples from the 13 countries of the Middle East sourced from the Global Initiative on Sharing All Influenza Data (GISAID)., Findings: We identified 2200 distinct genome variants including 129 downstream gene variants, 298 frame shift variants, 789 missense variants, 1 start lost, 13 start gained, 1 stop lost, 249 synonymous variants and 720 upstream gene variants. The most common, high impact variants were 10818delTinsG, 2772delCinsC, 14159delCinsC and 2789delAinsA. These high impact variant ultimately results in 36 number of mutations on spike glycoprotein. Variant alignment and phylogenetic tree generation indicates that samples from Iran likely introduced COVID-19 to the rest of the Middle East., Interpretation: The phylogenetic and variant analysis provides unique insight into mutation types in genomes. Initial introduction of COVID-19 was most likely due to Iranian transmission. Some countries show evidence of novel mutations and unique strains. Increased time in small populations is likely to contribute to more unique genomes. This study provides more in depth analysis of the variants affecting in the region than any other study., (Crown Copyright © 2021. Published by Elsevier Ltd. All rights reserved.) more...

Objectives: To summarize the outcomes of the coronavirus disease 2019 infections in the Eastern Mediterranean Region (EMR) in the first 4 months of the pandemic., Methods: A meta-analysis approach was used in this context. We used the aggregate data from the World Health Organization Regional Office for the EMRO (until 26 May 2020) to generate this report., Results: An analysis of official data from all 22 countries and territories in the Middle East, North Africa, the Horn of Africa, and Central Asia K=22 (a total of 438,717 cases) was performed. The total number of cases, recovered cases were 438,717,228,986,  and deaths was 11,290 in the EMR. Meta-analytic pooling of the point estimates of recovery rate per country in the EMR was 52.5% (95% CI 52.3% - 52.6%). The lowest recovery rates were in Somalia (4.3%), and the highest rates were in Tunisia (87.4%). Meta-analytic pooling of the point estimates of death rate per country in the EMR yielded 3.85% [95% CI 3.80% - 3.9%]. Meta-analytic pooling of the point estimates of recovery rate per country in the Gulf Cooperation Council countries was 46.1% (95% CI 45.8% - 46.3%). Meta-analytic pooling of the point estimates of death rate per country in the Gulf Cooperation Council countries was 0.6% (95% CI 0.50% - 0.65%)., Conclusion: Wide variability was found between EMR countries in recovery and mortality, implying the possible impact of resource availability, and genetic and environmental factors on the morality and recovery of the COVID-19. more...

Arabian Gulf University (AGU) follows a curriculum based on Problem Based Learning (PBL). PBL is a learner-centered approach that empowers students for life-long learning. Students are taught through problems that are designed based on global health problems customized to the local needs. The classroom teaching is complemented through adjunct programs like community health activities and professional skills program. Medical education aims to meet the changing needs of society. Demographics, disease epidemiology and healthcare needs of the gulf countries have changed over 38 years since the inception of AGU. To keep pace with the changing demands, it is imperative that the curriculum is reviewed in the light of advances in technology and newer techniques of medical education.In the present article the curriculum at AGU is reviewed based on the predictors for future medical education and alternative teaching methods that can be integrated to optimize the student outputs are explored., Competing Interests: Declaration of conflicting interests:The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2020.) more...

Context: Fluoroquinolones are the most effective antibiotics against Pseudomonas aeruginosa ; many strains, however, have shown resistance due to mutations in DNA gyrase, topoisomerase IV, or in the efflux pumps. Little is known about P. aeruginosa efflux pump resistance mechanisms in the Kingdom of Bahrain., Aim: The aim was to study efflux pump-mediated fluoroquinolone resistance among P. aeruginosa isolates using phenotypic (E-test and agar dilution) and genotypic (real-time-polymerase chain reaction [RT-PCR]) methods., Materials and Methods: Fifty ciprofloxacin-resistant P. aeruginosa isolates were included in this study. Genus and species of P. aeruginosa were confirmed by conventional PCR. The minimum inhibitory concentration (MIC) of ciprofloxacin with and without carbonyl cyanide 3-chlorophenylhydrazone (CCCP) was determined by E-test and agar dilution test. The overexpression of genes MexB, MexD, MexF , and MexY was measured by RT-PCR., Results: All isolates were confirmed as P. aeruginosa . Among the fifty isolates, four showed reduction in ciprofloxacin MIC after addition of CCCP. These four isolates showed upregulation of expression of at least one of the four genes by RT-PCR. The mean gene expression of MexB, MexD, MexF , and MexY increased by 1.6, 4.65, 3.4, and 3.68-fold, respectively., Conclusion: The results demonstrate the presence and type of efflux pump overexpression, mandating for large multicentric studies., Competing Interests: There are no conflicts of interest., (Copyright: © 2020 International Journal of Applied and Basic Medical Research.) more...

Introduction: Carbapenem-resistant Pseudomonas aeruginosa has emerged as a life-threatening infectious agent worldwide. Carbapenemase genes are reported to be some of the most common mechanisms for carbapenem resistance in P. aeruginosa . No reports are available from the Kingdom of Bahrain about carbapenem resistance and the underlying cause. In this study, we determined to study the presence of the metallo-beta-lactamase ( MβL ) genes of VIM family and NDM-1 in carbapenem-resistant P. aeruginosa strains., Methodology: Fifty carbapenem-resistant P. aeruginosa isolates were obtained from three main hospitals of Bahrain. They were subjected to antimicrobial susceptibility testing by disc diffusion test. Subsequently, MβL was detected by imipenem-ethylene diamine tetraacetic acid (EDTA) combined disc test and conventional polymerase chain reaction., Results: Among 50 P. aeruginosa strains, 40 (80%) were imipenem resistant. Among the 40 imipenem-resistant strains, 35 (87.5%) strains were positive for the imipenem-EDTA combined disc test, and 21 (52%) were carrying MβL genes. Nineteen (47.5%) strains were positive for the VIM gene; one (2.5%) strain was carrying the NDM-1 gene, while one strain was carrying both the VIM and NDM-1 genes. None of the imipenem sensitive strains carried the VIM or NDM-1 gene., Conclusion: This is the first study to report the presence of the VIM family gene and NDM-1 genes in imipenem-resistant P. aeruginosa isolates in the Kingdom of Bahrain. The study also confirms the multiple drug resistance by the MβL strains, attention should therefore from now on, be focused on prevention of further spread of such isolates by firm infection control measures, and to reduce its threat to public health., Competing Interests: There are no conflicts of interest. more...

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., (Copyright © 2016 Elsevier Ltd. All rights reserved.) more...

Objective: To detect the presence of specific CTX-M class of extended spectyum β-lactamases (ESBLs) in a collection of cephalosporin-resistant Enterobacteriaceae isolates from Bahrain., Methods: A 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., Results: A 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., Conclusions: This 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., (Copyright © 2014 Hainan Medical College. Published by Elsevier B.V. All rights reserved.) more...

Objective: To determine the molecular epidemiology of extended-spectrum β-lactamase (ESBL) by testing a cohort of clinical ESBL-producing bacterial isolates that were isolated in the Kingdom of Bahrain., Methods: ESBL producing Enterobacteriaceae isolates (based on phenotypic tests) were collected from Microbiology Laboratory of the Salmaniya Medical Complex, Bahrain between January-June 2006. Antibiotic susceptibility to a panel of antibiotics was performed and bla(CTX-M) genes were detected by multiplex PCR., Results: A total of 230 isolates (Escherichia coli, n=180; Klebsiella pneumoniae, n=50) were studied, 98% were CTX-M type. For Escherichia coli isolates, 65 (36.1%) harbored CTXM+TEM combination and 68 (37.8%) had CTX-M alone. In contrast, for Klebsiella pneumoniae isolates only 5 (10.0%) harbored the CTX-M combination, and none had CTX-M only. The bla(CTX-M) gene was found predominantly in urine isolates (n=145/230; 63.0%). Sensitivity to imipenem and nitrofurantoin was 100% and 60%, respectively. CTX-M carriage was associated with the resistance to fluoroquinolones, trimethoprim-sulfamethoxazole and aminoglycosides., Conclusions: Our study documentes high prevalence of CTX-M ESBL type among Escherichia coli and Klebsiella from the Kingdom of Bahrain. The apparent dissemination of CTX-M producers could represent a substantial barrier in the treatment of community-acquired infections. The use of extended-spectrum cephalosporins, quinolones, and aminoglycosides is compromised, leaving carbapenems as the therapeutic option for severe infections caused by ESBL producers., (Copyright © 2011 Hainan Medical College. Published by Elsevier B.V. All rights reserved.) more...

Background: The vacuolating cytotoxin and the cytotoxinassociated protein, encoded by vacA and cagA, respectively, are important virulence determinants of Helicobacter pylori., Objective: The aim of this study was to perform vacA genotyping and evaluate its association with cagA genotype and clinical outcome., Methods: One hundred and twenty H. pylori strains were isolated from dyspeptic patients (29 with peptic ulcer, 91 with non-ulcer dyspepsia). Genotype was determined by PCR., Results: Seventy-nine (66%) of 120 strains had the vacA signal sequence genotype s1 and 41 (34%) had the type s2. The vacA middle-region types m1 and m2 were detected in 56 (47%) and 64 (53%) strains, respectively. The combinations s1-m1 (n=56 [47%] and s2-m2 (41 [34%]) occurred more frequently than s1-m2 (23 [19.2%]; p=0.001). No strain with the combination s2-m1 was found. All patients with peptic ulcers harbored type s1 strains compared to 75 (82.4%) of 91 patients with non-ulcer dyspepsia (p=0.01). The vacA genotype s1 was associated with the presence of cagA (p <0.0001). The cagA gene was detectable in 38 (31.6%) of 120 isolates and present in all 29 patients with ulcer compared to nine of 91 with non-ulcer dyspepsia (p <0.001)., Conclusion: Helicobacter pylori strains of vacA type s1 and the combination of s1-m1 were associated with peptic ulceration and the presence of cagA gene. more...

Background: To assess the prevalence of extended spectrum beta-lactamase (ESBL) producing Escherichia coli and Klebsiella strains in nosocomial and community-acquired infections., Methodology: The study was conducted at a centralized microbiology laboratory in the Eastern Province of Saudi Arabia. Laboratory records (January 2004 - December 2005) were assessed. Associated resistance to a panel of antibiotics was determined., Results: A total of 6,750 Gram-negative organisms were assessed for ESBL-phenotype. ESBL was detected in 6% (409/6,750) of isolates, the majority of which were E. coli (83%). ESBL producers were significantly higher among isolates from in-patients 15.4% (143/927) versus out-patients (4.5%; 266/5,823); p < 0.05. Old age (older than 60 years) represented a significant risk for having an ESBL-producing pathogen. Urine was the major source of ESBL isolates in in-patients (46.1%) and out-patients (74.4%). The proportion of urinary E. coli isolates which were ESBL producers was significantly higher among in-patients (53/506; 10.4%) compared to out-patients (182/4,074; 4.4%); p<0.05. Old age (older than 60 years) represented a significant risk for having an ESBL-producing pathogen. Urine was the major source of ESBL isolates in in-patients (46.1%) and out-patients (74.4%). The proportion of urinary E. coli isolates which were ESBL producers was significantly higher among in-patients (53/506; 10.4%) compared to out-patients (182/4,074; 4.4%); p<0.05. Among in-patients, 60% of the ESBL associated infections were nosocomial. All were sensitive to imipenem but high levels of resistance to gentamicin, amikacin, amoxicillin-clavulanic acid and ciprofloxacin was shown., Conclusion: The findings document evidence of the spread of multiresistant ESBL-producers into the community. This has significant implications for patient management, and indicates the need for increased surveillance and molecular characterization of these isolates. more...

Objectives: To determine the occurrence of extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae in Bahrain., Methods: Retrospective analysis of records (January 2005-December 2006) at the Microbiology Laboratory of the Salmaniya Medical Complex, Bahrain which is the major national diagnostic laboratory., Results: Out of a total of 11,886 member of family of Enterobacteriaceae isolated, 2695 (22.6%) were ESBL producers. Majority of ESBL isolates were from inpatients (n=2363; 87.7%). Escherichia coli (52.2%) and Klebsiella pneumoniae (24.3%) were predominant and distributed comparatively in the hospital wards while Proteus spp. (17.6%) was predominant in medical wards. Urine was the major source (52.2%) with low occurrence in blood cultures. No carbapenem resistant isolates was identified but resistance to three classes of antibiotics was exhibited by >25% of the isolated ESBL strains. Nitrofurantoin resistance was identified in 38.2% of urinary isolates., Conclusion: This is the first report from Bahrain and it indicates that the prevalence of ESBL-producing isolates is high. Carbapenems were the most active drug against the ESBL-producing isolates. We recommend strict infection control to prevent trafficking into the community. more...

There are no data describing the genetic make-up of Campylobacter strains (an important aetiological agent of diarrhoea) circulating in the Arabian Gulf region. Here, the molecular characterization of two virulence genes in Campylobacter jejuni from Bahrain and the relationship with clinical infection are reported. Molecular screening for cytolethal distending toxin (cdtB) and invasion-associated marker (iam) genes was carried out on C. jejuni stool isolates collected from January 2002 to January 2004 in Bahrain. The molecular characterization was correlated with the patients' socio-demographic and clinical parameters. Of the 96 C. jejuni strains tested, 50 (52 %) were cdtB+/iam+, 30 (31 %) were cdtB+/iam- and 16 (17 %) were cdtB-/iam-. Sixty-nine per cent (66/96) of patients were less than 3 years old, with significantly higher detection of cdtB+/iam+ and cdtB+/iam- strains (P < 0.001 and P < 0.01, respectively) in this age group. Seventy patients (73 %) were symptomatic. In the group that were less than 3 years old, 62 and 85 % of those with cdtB+/iam+ and cdtB+/iam- strains, respectively, were symptomatic compared with 100 % for those over 3 years of age. However, the presence of cdtB-/iam- strains still resulted in clinical infection in the children under 3 years but not in the older patients. This is the first report describing the molecular characterization of virulence genes in Campylobacter isolates from this region. The findings indicate that strains of different virulence genetic make-up are circulating in the population, with children under the age of 3 years being most vulnerable. Further work on the molecular characterization, gene expression and determination of the invasive phenotypes of C. jejuni strains circulating in different regions is needed. more...

Objectives: To investigate the organisms causing neonatal sepsis and their modifications over an extended period, to assess their changing sensitivities to antibiotics and to verify whether the policy for screening pregnant women for group B streptococci (GBS) carriage is desirable in our settings., Subjects and Methods: Medical records of all infants with positive blood culture from the Neonatal Intensive Care Unit at Salmaniya Medical Complex between 1991 and 2001 and Bahrain Defense Force Hospital between 1999 and 2001 were reviewed., Results: Of the 7,978 neonates in both hospitals 335 (4.19%) had culture-proven bacteremia. Gram-positive bacteria were isolated at constant rate over the 11-year period. The main agents isolated were coagulase-negative Staphylococcus (CoNS) in 138 cases (41%), Staphylococcus aureus in 28 newborns (8%) and GBS in 26 patients (7.8%, 0.2/1,000 live births). All of them were sensitive to penicillin G, erythromycin and clindamycin. Gram-negative bacteria were declining but Escherichia coli was isolated in 35 cases (10%). Of special concern is the increasing percentage (5.7%) of Candida isolation. No clear trend toward increasing resistance was observed, although a major difference among the two institutions was evident. Klebsiella and Enterobacter spp. showed resistance to many of the antibiotics tested, thereby posing difficult therapeutic choices., Conclusion: Good quality specimens are essential to evaluate the role of CoNS. The increasing threat of fungal infection must be carefully tackled. Specifically tailored policies for GBS prevention must be defined according to the local epidemiology., ((c) 2006 S. Karger AG, Basel) more...

Objectives: To investigate the effect of pre-exposure antibiotics on cytolethal distending toxin (CDT) production and toxigenic effect of C. jejuni., Methods: Sonicates and filtrates were prepared from known cdt+ and cdt- isolates of C. jejuni which had been pre-exposed to varying concentrations (MIC, 1/2 MIC, 1/4 MIC, 1/8 MIC) of erythromycin and ciprofloxacin. The CDT toxigenic effect was examined using INT 407 and HeLa cells., Results: A trend of increased toxigenic effect was observed with pre-exposure to antibiotics. This was more pronounced with erythromycin pre-exposure compared to ciprofloxacin. Although a trend of increasing toxigenic effect with decreasing antibiotic concentration was demonstrable, some differences were observed between isolates. In one isolate the increased toxigenic effect was statistically significant (P<0.05) at 1/4 MIC in INT 407 cells and at 1/8 MIC in HeLa cells., Conclusions: This study provides evidence of an association between CDT production by C. jejuni and pre-exposure to antibiotics. Pre-exposure to ciprofloxacin and erythromycin at concentrations below MICs could potentiate CDT activity. Further work is needed to elucidate the mechanism involved. We recommend that these antibiotics be used in the treatment of C. jejuni enteritis only when strongly indicated and with careful monitoring of patients. more...

An essential element in the control of tuberculosis is the rapid, sensitive and specific identification of the causative agent. Until now, screening and diagnosis are largely based on clinical signs, radiological examination, tuberculin tests, sputum examination under the microscope, or culture for mycobacteria. Tuberculin tests lack specificity and only give an indication of previous exposure to mycobacteria. Direct microscopic examination of sputum is neither specific nor sensitive enough, and mycobacterial isolation is time-consuming. As an alternative to these classical methods, new nucleic acid-based technologies show promise as a more rapid, sensitive, and specific means of identification of mycobacteria. Two commercial standardized nucleic acid-based amplification techniques have been reported to yield reliable results within 5 to 7 hrs. Roche Amplicor MTB (Roche Diagnostic System, Somerville, N.J.) and Gen-Probe AMTB (Gen-Probe Inc., San Diego, Calif.). The amplified target is part of the 16S rRNA gene which is common to all the mycobacteria. An attempt has been made to describe the use of the target DNA, SenX3-RegX3, in a multiplex PCR to detect and differentiate M. tuberculosis from other mycobacteria directly from clinical specimens. more...

Objective: The aim of this study was to evaluate the prevalence of resistance among 83 Helicobacter pylori isolates cultured from biopsies taken during routine endoscopies in 1998-1999., Methods: Minimum Inhibitory Concentration of amoxicillin, tetracycline, clarithromycin and metronidazole were determined by Epsilometer test., Results: Forty-seven strains (57%) were resistant to metronidazole, and 27 (32.5%) were resistant to clarithromycin. Twenty of the 27 strains resistant to clarithromycin were also resistant to metronidazole. None of the strains were resistant to amoxicillin or tetracycline., Conclusion: A high percentage of patients from Bahrain were infected with resistant strains of Helicobacter pylori. Antibiotic resistance monitoring is very important and unified national treatment policies are needed. more...

Ninety-one isolates of non-penicillinase-producing Neisseria gonorrhoeae from patients in Bahrain were tested for serotype, auxotype, and antibiotic susceptibility. Ten serovars and three auxotypes were found. Of the 91 isolates, 49 (54%) were serovar IB-5/7, 59 (65%) had a penicillin MIC greater than or equal to 1 mg/l, 39 (45%) had a cefuroxime MIC greater than or equal to 0.5 mg/l, and 63 (69%) had a tetracycline MIC of greater than or equal to 4 mg/l. No spectinomycin or high-level tetracycline resistance was seen. Seventy of the 91 isolates were tested against ciprofloxacin and ceftriaxone, and 40 (57%) and 26 (37%) had MICs greater than or equal to 0.03 mg/l, respectively. DNA from two penicillin-resistant isolates was capable of transforming recipient strain FA19 to donor level of penicillin and cephalosporin resistance in four steps. The first three steps were indicative of the acquisition of known resistance mutations. The existence of the fourth level transformants, with the ability of donor DNA to transform strain FA140 to higher levels of resistance, suggest the presence of another resistance mutation. more...

Non-penicillinase producing Neisseria gonorrhoeae isolated at St Mary's Hospital, London were examined for the prevalence of resistance to penicillin and for decreased susceptibility to cefuroxime. Of the 941 non-PPNG tested 100 (10.6%) were resistant to penicillin (minimum inhibitory concentration, MIC, greater than or equal to 1 mg/l) and were considered to be chromosomally-resistant N gonorrhoeae (CMRNG). Decreased susceptibility to cefuroxime (MIC, greater than or equal to 0.5 mg/l) was detected in 79% of the CMRNG. The CMRNG were also more often prototrophic and of serogroup IB than the remaining non-PPNG. The correlation coefficient for resistance to penicillin and cefuroxime was high, 0.79. Transformation experiments with both genetically-defined strains and transformants obtained using DNA from clinical isolates, showed that increased resistance to cephalosporins was acquired in three steps in close association with penicillin. We think this suggests that the loci controlling resistance to the cephalosporins are identical or closely linked to those controlling penicillin resistance. more...

A total of 160 consecutive isolates of Neisseria gonorrhoeae was collected over a 3-month period. They were tested for their susceptibility to penicillin, erythromycin and spectinomycin and the auxotype and the serotype determined. We have evaluated two sampling methods, the collection of every fifth isolate and the first 20 isolates (10 male and 10 female) each month, to determine whether either is representative of the total population. There was no significant difference between either method of sampling and the total for detecting the predominant auxotypes and serovars or the distributions in antibiotic susceptibility. It is possible to monitor major changes in a gonococcal population, particularly susceptibility to antibiotics, using a sample of the total population. more...

A serological classification scheme for Neisseria gonorrhoeae was used to investigate the epidemiological associations between gonococcal serotype and other bacterial and host characters. Six hundred and fifty clinical isolates of non-penicillinase producing N gonorrhoeae from the Praed Street Clinic, St Mary's Hospital, were included in this study. The strains collected represented 41 serovars, although 485 (75%) of the 650 strains belonged to five serovars. Strains of serovar IA-1/2 were commonly isolated from the cervix and tended to be sensitive to penicillin and moderately resistant to erythromycin. Strains of serovar IB-1 showed bimodal patterns of susceptibility to both penicillin and erythromycin and were obtained equally from all anatomical sites. Strains of serovar IB-2 were isolated more often from the rectum and were associated with homosexually acquired infections, whereas those of serovar IB-3 were sensitive to erythromycin and were rarely isolated from the rectum. Strains of IB-5/7 were more resistant to penicillin and erythromycin than strains of other serovars. The serological classification of N gonorrhoeae is thus a powerful tool that may be used to study biological characteristics of the gonococcus, such as susceptibility to antimicrobials and site tropism. more...