Browsing by Author "Senok, Abiola"

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ACE2 polymorphisms impact COVID-19 severity in obese patients
(2022-12) Jalaleddine, Nour; Hachim, Mahmood Yaseen; Senok, Abiola; Al Heialy, Saba
Abstract: A strong association between obesity and COVID-19 complications and a lack of prognostic factors that explain the unpredictable severity among these patients still exist despite the various vaccination programs. The expression of angiotensin converting enzyme 2 (ACE2), the main receptor for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), is enhanced in obese individuals. The occurrence of frequent genetic single nucleotide polymorphisms (SNPs) in ACE2 is suggested to increase COVID-19 severity. Accordingly, we hypothesize that obesity-associated ACE2 polymorphisms increase the severity of COVID-19. In this study, we profiled eight frequently reported ACE2 SNPs in a cohort of lean and obese COVID-19 patients (n = 82). We highlight the significant association of rs2285666, rs2048683, rs879922, and rs4240157 with increased severity in obese COVID-19 patients as compared to lean counterparts. These co-morbid-associated SNPs tend to positively correlate, hence proposing possible functional cooperation to ACE2 regulation. In obese COVID-19 patients, rs2285666, rs879922, and rs4240157 are significantly associated with increased blood nitrogen urea and creatinine levels. In conclusion, we highlight the contribution of ACE2 SNPs in enhancing COVID-19 severity in obese individuals. The results from this study provide a basis for further investigations required to shed light on the underlying mechanisms of COVID-19 associated SNPs in COVID-19 obese patients.
Antimicrobial Activity of Phytic Acid: An Emerging Agent in Endodontics
(2021) Nassar, Rania; Naidoo, Nerissa; Kaklamanos, Eleftherios G; Senok, Abiola
Background: Phytic acid (IP6) is a promising and emerging agent, and because of its unique structure and distinctive properties, it lends itself to several applications in dentistry. Recently, IP6 was proposed as a potential chelating agent in endodontics. However, there is limited knowledge regarding its antimicrobial and antibiofilm effectiveness. The aims of this study, were therefore to evaluate the antimicrobial and antibiofilm activities of IP6 against a range of microbial species and compare these with ethylenediaminetetraacetic acid (EDTA) and sodium hypochlorite (NaOCl). The contact time required for IP6 to exert its bactericidal effect on Enterococcus faecalis was also determined. Methods: The inhibitory and biocidal activities of IP6, EDTA and NaOCl were assessed using a broth microdilution assay against 11 clinical and reference strains of bacteria and a reference strain of Candida albicans. The contact time required for various IP6 concentrations to eliminate planktonic cultures of E. faecalis was determined using a membrane filtration method according to BS-EN-1040:2005. IP6 bactericidal activity was also evaluated using fluorescent microscopy, and the antibiofilm activity of the test agents was also determined. Results: IP6 was biocidal against all tested microorganisms. At concentrations of 0.5%, 1% and 2%, IP6 required 5 min to exert a bactericidal effect on E. faecalis, while 5% IP6 was bactericidal after 30 s. IP6 also eradicated biofilms of the tested microorganisms. In conclusion, IP6 had notable antimicrobial effects on planktonic and biofilm cultures and exhibited rapid bactericidal effects on E. faecalis. This research highlighted, for the first time the antimicrobial and antibiofilm properties of IP6, which could be exploited, not only in dental applications, but also other fields where novel strategies to counter antimicrobial resistance are required.
Antimicrobial resistance in Streptococcus pneumoniae: a retrospective analysis of emerging trends in the United Arab Emirates from 2010 to 2021
(2023-11) Senok, Abiola
Abstract: Introduction: Although pneumococcal conjugate vaccines (PCV) have been effective in reducing the burden of Streptococcus pneumoniae infections, there is a paucity of data on the relationship with antimicrobial resistance (AMR) trends in the Arabian Gulf region. This study was carried out to assess S. pneumoniae resistance trends in the United Arab Emirates (UAE) where PCV-13 vaccination was introduced in 2011. Methods: Retrospective analysis of S. pneumoniae demographic and microbiological data collected as part of the national AMR surveillance program from 2010 to 2021 was carried out. A survey of reporting sites and hand searching of annual reports of local health authorities was carried out to identify data on S. pneumoniae serotypes as this is not included in the AMR surveillance database. Results: From 2010 to 2021, 11,242 non-duplicate S. pneumoniae isolates were reported, increasing from 324 in 2010 to 1,115 in 2021. Factoring in annual increment in the number of surveillance sites, the number of isolates per site showed an upward trajectory from 2015 to 2018 and declined in 2020 with the onset of the pandemic. The majority of isolates (n/N = 5,751/11,242; 51.2%) were from respiratory tract specimens with 44.5% (n/N = 2,557/5,751) being nasal colonizers. Up to 11.9% (n/N = 1,337/11,242) were invasive pneumococcal disease (IPD) isolates obtained from sterile site specimens including blood (n = 1,262), cerebrospinal (n = 52), pleural (n = 19) and joint (n = 4) fluid; and were predominantly from pediatric patients. The downward trend for amoxicillin and for penicillin G at the non-meningitis and meningitis as well as oral penicillin breakpoints was statistically significant. In contrast, increasing trends of resistance were seen for levofloxacin, moxifloxacin, trimethoprim/sulfamethoxazole and erythromycin. IPD and non-IPD isolates showed similar demographic and AMR trends. None of the surveillance sites carried out S. pneumoniae serotyping and handsearching of annual reports did not yield this information.
Carbapenem resistant Enterobacterales in the United Arab Emirates: a retrospective analysis from 2010 to 2021
(2023-12) Senok, Abiola
Abstract: Background: Carbapenem-resistant Enterobacterales (CRE) are spreading in the United Arab Emirates (UAE) where their dissemination is facilitated by international travel, trade, and tourism. The objective of this study is to describe the longitudinal changes of CRE as reported by the national AMR surveillance system of the UAE. Methods: In this study, we retrospectively describe CRE isolated from 317 surveillance sites, including 87 hospitals and 230 centers/clinics from 2010 to 2021. The associated clinical, demographic, and microbiological characteristics are presented by relying on the UAE national AMR surveillance program. Data was analyzed using WHONET microbiology laboratory database software (http://www.whonet.org). Results: A total of 14,593 carbapenem resistant Enterobacterales were analyzed, of which 48.1% were carbapenem resistant Klebsiella pneumoniae (CRKp), 25.1% carbapenem resistant Escherichia coli (CREc), and 26.8% represented 72 other carbapenem resistant species. Carbapenem resistant strains were mostly associated with adults and isolated from urine samples (36.9% of CRKp and 66.6% of CREc) followed by respiratory samples (26.95% for CRKp) and soft tissue samples (19.5% for CRKp). Over the studied period carbapenem resistance rates remained high, especially in K. pneumoniae, and in 2021 were equivalent to 67.6% for imipenem, 76.2% for meropenem, and 91.6% for ertapenem. Nevertheless, there was a statistically significant decreasing trend for imipenem and meropenem resistance in Klebsiella species (p < 0.01) while the decrease in ertapenem resistance was non-significant. Concerning E. coli, there was a statistically significant decreasing trend for meropenem and imipenem resistance over the 12 years, while ertapenem resistance increased significantly with 83.8% of E. coli exhibiting ertapenem resistance in 2021. Resistance rates to ceftazidime and cefotaxime remained higher than 90% (in 2021) for CRKp and cefotaxime rates increased to 90.5% in 2021 for CREc. Starting 2014, resistance to colistin and tigecycline was observed in carbapenem resistant Enterobacterales. CRE were associated with a higher mortality (RR: 6.3), admission to ICU (RR 3.9), and increased length of stay (LOS; 10 excess inpatient days per CRE case). Conclusion: This study supports the need to monitor CRE in the UAE and draws attention to the significant increase of ertapenem resistance in E. coli. Future surveillance analysis should include a genetic description of carbapenem resistance to provide new strategies.
Cell free ACE2 RNA: A potential biomarker of COVID-19 severity
(2023) Jalaleddine, Nour; Hachim, Mahmood; Senok, Abiola; Al Heialy, Saba
Abstract: Despite the downward trend of COVID-19 pandemic and increased immunity of the general population, COVID19 is still an elusive disease with risks due to emerging variants. Fast and reliable diagnosis of COVID-19 disease would allow better therapeutic interventions for patients at risk to develop more severe outcomes. Cell-free RNAs (cfRNAs) have been proven to be an effective biomarker in cancer and infectious diseases. It has been reported that cfRNAs are amplified in the bloodstream of these patients and at earlier stages of the disease, reflecting tissue damage. Hence, we hypothesize that cfRNAs may serve as a potential indicator of COVID-19 disease severity. To our knowledge, this is the first report to display a significant link between COVID-19 severity and cfRNA of angiotensin converting enzyme-2 (ACE2), the receptor for SARS-CoV-2 virus. qRT-PCR analysis of liquid biopsies from COVID-19 patients (n = 82) displayed a significant increase in ACE2-cfRNA levels in patients with severe manifestations. This finding correlated with blood biomarkers (ANC, WBC, and Creatinine) that were also significantly increased in these patients. We previously showed that bronchial cells from obese subjects express higher ACE2 levels, hence, we further analysed the involvement of obesity as a main contributor to severe outcomes. We confirm a significant increase of ACE2-cfRNA in the plasma of obese/overweight (Ob/Ov) COVID-19 patients compared to lean subjects, with no observed significant change in blood biomarkers. These findings suggest that monitoring ACE2-cfRNAs, as a biomarker, during COVID-19 infection may allow for better disease management, specifically for severe-COVID-19 patients.
Characterisation of S. aureus/ MRSA CC1153 and review of mobile genetic elements carrying the fusidic acid resistance gene fusC
(2021) Nassar, Rania; Senok, Abiola
Abstract: While many data on molecular epidemiology of MRSA are available for North America, Western Europe and Australia, much less is known on the distribution of MRSA clones elsewhere. Here, we describe a poorly known lineage from the Middle East, CC1153, to which several strains from humans and livestock belong. Isolates were characterised using DNA microarrays and one isolate from the United Arab Emirates was sequenced using Nanopore technology. CC1153 carries agr II and capsule type 5 genes. Enterotoxin genes are rarely present, but PVL is common. Associated spa types include t504, t903 and t13507. PVL-positive CC1153-MSSA were found in Egyptian cattle sufering from mastitis. It was also identifed among humans with skin and soft tissue infections in Saudi Arabia, France and Germany. CC1153-MRSA were mainly observed in Arabian Gulf countries. Some isolates presented with a previously unknown SCCmec/SCCfus chimeric element in which a mec B complex was found together with the fusidic acid resistance gene fusC and accompanying genes including ccrA/B-1 recombinase genes. Other isolates carried SCCmec V elements that usually also included fusC. Distribution and emergence of CC1153-MRSA show the necessity of molecular characterization of MRSA that are resistant to fusidic acid. These strains pose a public health threat as they combine resistance to beta-lactams used in hospitals as well as to fusidic acid used in the community. Because of the high prevalence of fusC-positive MRSA in the Middle East, sequences and descriptions of SCC elements harbouring fusC and/or mecA are reviewed. When comparing fusC and its surrounding regions from the CC1153 strain to available published sequences, it became obvious that there are four fusC alleles and fve distinct types of fusC gene complexes reminiscent to the mec complexes in SCCmec elements. Likewise, they are associated with diferent sets of ccrA/B recombinase genes and additional payload that might include entire mec complexes or SCCmec elements.
Clinical Impact of the BIOFIRE Blood Culture Identification 2 Panel in Adult Patients with Bloodstream Infection: A Multicentre Observational Study in the United Arab Emirates
(2023) Senok, Abiola; Olowoyeye, Victory
Abstract: Rapid pathogen identification is key to the proper management of patients with bloodstream infections (BSIs), especially in the intensive care setting. This multicentre study compared the time to pathogen identification results in 185 patients admitted to intensive care with a confirmed BSI, using conventional methods (n = 99 patients) and upon implementation of the BIOFIRE® Blood Culture Identification 2 (BCID2) Panel, a rapid molecular test allowing for the simultaneous identification of 43 BSI-related nucleic acids targets (n = 86 patients). The median time to result informing optimal antibiotic therapy was significantly shorter following the implementation of the BCID2 Panel (92 vs. 28 h pre vs. post BCID2 implementation; p < 0.0001). BCID2 usage in addition to conventional methods led to the identification of at least one pathogen in 98.8% patients vs. 87.9% using conventional methods alone (p = 0.003) and was associated with a lower 30-day mortality (17.3% vs. 31.6%, respectively; p = 0.019). This study at three intensive care units in the United Arab Emirates therefore demonstrates that, in addition to conventional microbiological methods and an effective antimicrobial stewardship program, the BCID2 Panel could improve the clinical outcome of patients admitted to the intensive care unit with a confirmed BSI.
Clinical Impact of the BIOFIRE Blood Culture Identification 2 Panel in Adult Patients with Bloodstream Infection: A Multicentre Observational Study in the United Arab Emirates
(2023) Senok, Abiola; Olowoyeye, Victory
Abstract: Rapid pathogen identification is key to the proper management of patients with bloodstream infections (BSIs), especially in the intensive care setting. This multicentre study compared the time to pathogen identification results in 185 patients admitted to intensive care with a confirmed BSI, using conventional methods (n = 99 patients) and upon implementation of the BIOFIRE® Blood Culture Identification 2 (BCID2) Panel, a rapid molecular test allowing for the simultaneous identification of 43 BSI-related nucleic acids targets (n = 86 patients). The median time to result informing optimal antibiotic therapy was significantly shorter following the implementation of the BCID2 Panel (92 vs. 28 h pre vs. post BCID2 implementation; p < 0.0001). BCID2 usage in addition to conventional methods led to the identification of at least one pathogen in 98.8% patients vs. 87.9% using conventional methods alone (p = 0.003) and was associated with a lower 30-day mortality (17.3% vs. 31.6%, respectively; p = 0.019). This study at three intensive care units in the United Arab Emirates therefore demonstrates that, in addition to conventional microbiological methods and an effective antimicrobial stewardship program, the BCID2 Panel could improve the clinical outcome of patients admitted to the intensive care unit with a confirmed BSI.
Coinfections in Patients Hospitalized with COVID-19: A Descriptive Study from the United Arab Emirates
(2021) Senok, Abiola; Nassar, Rania; Hachim, Mahmood Yaseen; Al Suwaidi, Hanan; Alsheikh-Ali, Alawi
Purpose: Microbial coinfections in COVID-19 patients carry a risk of poor outcomes. This study aimed to characterize the clinical and microbiological profiles of coinfections in patients with COVID-19. Methods: A retrospective review of the clinical and laboratory records of COVID-19 patients with laboratory-confirmed infections with bacteria, fungi, and viruses was conducted. Only adult COVID-19 patients hospitalized at participating health-care facilities between February 1 and July 31, 2020 were included. Data were collected from the centralized electronic system of Dubai Health Authority hospitals and Sheikh Khalifa General Hospital Umm Al Quwain. Results: Of 29,802 patients hospitalized with COVID-19, 392 (1.3%) had laboratory-confirmed coinfections. The mean age of patients with coinfections was 49.3±12.5 years, and a majority were male (n=330 of 392, 84.2%). Mean interval to commencement of empirical antibiotics was 1.2±3.6) days postadmission, with ceftriaxone, azithromycin, and piperacillin–tazobactam the most commonly used. Median interval between admission and first positive culture (mostly from blood, endotracheal aspirates, and urine specimens) was 15 (IQR 8–25) days. Pseudomonas aeruginosa, Klebsiella pneumoniae, and Escherichia coli were predominant in first positive cultures, with increased occurrence of Stenotrophomonas maltophilia, methicillin-resistant Staphylococcus aureus, Acinetobacter baumannii, Candida auris, and Candida parapsilosis in subsequent cultures. The top three Gram-positive organisms were Staphylococcus epidermidis, Enterococcus faecalis, and Staphylococcus aureus. There was variability in levels of sensitivity to antibiotics and isolates harboring mecA, ESBL, AmpC, and carbapenemase-resistance genes were prevalent. A total of 130 (33.2%) patients died, predominantly those in the intensive-care unit undergoing mechanical ventilation or extracorporeal membrane oxygenation. Conclusion: Despite the low occurrence of coinfections among patients with COVID-19 in our setting, clinical outcomes remained poor. Predominance of Gram-negative pathogens, emergence of Candida species, and prevalence of isolates harboring drug-resistance genes are of concern.
COVID-19 Transcriptomic Atlas: A Comprehensive Analysis of COVID-19 Related Transcriptomics ‎Datasets
(2021) Alqutami, Fatma; Senok, Abiola; Hachim, Mahmood Yaseen
Background:‎ To develop anti-viral drugs and vaccines, it is crucial to understand the molecular basis and pathology of ‎COVID-19. An increase in research output is required to generate data and results at a faster rate, ‎therefore bioinformatics plays a crucial role in COVID- 19 research. There is an abundance of ‎transcriptomic data from studies carried out on COVID- 19, however, their use is limited by the ‎confounding factors pertaining to each study. The reanalysis of all these datasets in a unified approach ‎should help in understanding the molecular basis of COVID-19. This should allow for the identification of ‎COVID-19 biomarkers expressed in patients and the presence of markers specific to disease severity ‎and condition.‎ Aim: In this study, we aim to use the multiple publicly available transcriptomic datasets retrieved from the ‎Gene Expression Omnibus (GEO) database to identify consistently differential expressed genes in ‎different tissues and clinical settings.‎ Materials and Methods: A list of datasets was generated from NCBI’s GEO using the GEOmetadb package through R software. ‎Search keywords included SARS-COV-2 and COVID-19. Datasets in human tissues containing more than ‎ten samples were selected for this study. Differentially expressed genes (DEGs) in each dataset were ‎identified. Then the common DEGs between different datasets, conditions, tissues and clinical settings ‎were shortlisted.‎ Results: Using a unified approach, we were able to identify common DEGs based on the disease conditions, ‎samples source and clinical settings. For each indication, a different set of genes have been identified, ‎revealing that a multitude of factors play a role in the level of gene expression.‎ Conclusion: Unified reanalysis of publically available transcriptomic data showed promising potential in identifying ‎core targets that can explain the molecular pathology.
Detection of Clostridium difficile antigen and toxin in stool specimens: Comparison of the C. difficile quik chek complete enzyme immunoassay and GeneXpert C. difficile polymerase chain reaction assay
(2017) Senok, Abiola
Background/Aims: Accurate and rapid laboratory diagnosis of Clostridium difficile infections (CDI) remains a significant challenge. A two‑step algorithm for detection of toxigenic C. difficile in stool based on initial screening for glutamate dehydrogenase assay followed by confirmation by toxin A+B detection using an enzyme immunoassay (EIA) or molecular assay has been proposed. We aimed to evaluate the C. difficile Quik Chek Complete® (QCC‑EIA) versus the GeneXpert® C. difficile polymerase chain reaction (PCR) assay in this two‑step algorithm. Materials and Methods: Two hundred and ten liquid stool samples obtained between June 2014 and June 2015 from patients suspected of CDI were tested by the QCC‑EIA and GeneXpert PCR assay. The GeneXpert assay was used as the reference standard to calculate the QCC‑EIA sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). Results: Of the 210 stool samples tested, 43 (20.5%) were positive by QCC‑EIA, while 31 (14.8%) were positive by GeneXpert assay. The sensitivity and specificity of the QCC‑EIA were found to be 100 and 93%, respectively; the PPV and NPV were 72 and 100%, respectively. The binary toxin was detected in 12 (38.7%) and tcdC gene deletion in 3 (9.6%). Conclusions: The low specificity of QCC‑EIA makes it less reliable as a confirmatory test for CDI diagnosis. This test may be used as a screening test in a two‑step algorithm when combined with a molecular assay or another confirmatory test.
The Effect of Chlorhexidine on Bacterial Contamination of Hall Technique Elastomeric Orthodontic Separators and Gingival Health: A Pilot Study
(2023) AlNoman, Nada; Al Halabi, Manal; Kowash, Mawlood; Hassan Khamis, Amar; Salami, Anas; Senok, Abiola; Nassar, Rania; Hussein, Iyad
Objective: To study the effect of chlorhexidine on elastomeric orthodontic separators (EOS) bacterial-colonisation and gingival-health in Hall technique (HT) patients. Material and Methods: Prospective invivo pilot clinical study of EOS bacterial colonisation and primary-molar gingival health assessment in 20 patients (mean age 5.45±1.27 years) requiring bilateral HT crowns (40 teeth). One side received 1-minute 0.12% chlorhexidine-soaked-EOSs (Chx-EOSs), and the other side dry-EOSs (NoChx-EOSs). The EOSs were removed five-days later and underwent a bacterial enumeration technique. Plaque (PI) and Gingival (GI) indices were assessed pre-, five-days and three-months post-treatment. Wilcoxon-Signed-Rank/McNemar-Chi-square statistics were used (p<0.05). Results: Baseline unused/packaged EOSs’ sterility check yielded zero colony-forming-units (CFU) per millilitre, but 100% of the used EOSs became colonised by oral-microorganisms. An overall trend of lower mean CFU count in Chx-EOSs (3.415± 0.78 x105 CFU/ml) compared to NoChx-EOSs (6.157±1.48 x105 CFU/ml) was observed (p=0.009). Both NoChx-EOSs and ChxEOSs insertion sites showed evidence of gingivitis with no difference between PI and GI indices by site over time. Conclusion: There was a lower trend of bacterial colonization in chlorhexidine treated EOSs and an occurrence of gingivitis pre/post HT-treatment regardless of EOS type. The lack of difference in the gingival health may be inconclusive due to this pilot’s low power suggesting the need for robust large scale studies.
Effect of Common Medications on the Expression of SARS-CoV-2 Entry Receptors in Kidney Tissue
(2020) Tayoun, Ahmad Abou; Loney, Tom; Uddin, Mohammed; Senok, Abiola; Al Heialy, Saba; Alsheikh-Ali, Alawi
Abstract: Besides the respiratory system, severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infection was shown to affect other essential organs such as the kidneys. Early kidney involvement during the course of infection was associated with worse outcomes, which could be attributed to the direct SARS-CoV-2 infection of kidney cells. In this study, the effect of commonly used medications on the expression of SARS-CoV-2 receptor, angiotensin-converting enzyme (ACE)2, and TMPRSS2 protein in kidney tissues was evaluated. This was done by in silico analyses of publicly available transcriptomic databases of kidney tissues of rats treated with multiple doses of commonly used medications. Of 59 tested medications, 56% modified ACE2 expression, whereas 24% modified TMPRSS2 expression. ACE2 was increased with only a few of the tested medication groups, namely the renin-angiotensin inhibitors, such as enalapril, antibacterial agents, such as nitrofurantoin, and the proton pump inhibitor, omeprazole. The majority of the other medications decreased ACE2 expression to variable degrees with allopurinol and cisplatin causing the most noticeable downregulation. The expression level of TMPRSS2 was increased with a number of medications, such as diclofenac, furosemide, and dexamethasone, whereas other medications, such as allopurinol, suppressed the expression of this gene. The prolonged exposure to combinations of these medications could regulate the expression of ACE2 and TMPRSS2 in a way that may affect kidney susceptibility to SARS-CoV-2 infection. Data presented here suggest that we should be vigilant about the potential effects of commonly used medications on kidney tissue expression of ACE2 and TMPRSS2.
Emergence of highly resistant Candida auris in the United Arab Emirates: a retrospective analysis of evolving national trends
(2024-01) Senok, Abiola
Abstract: Introduction: The Centers for Disease Prevention and Control lists Candida auris, given its global emergence, multidrug resistance, high mortality, and persistent transmissions in health care settings as one of five urgent threats. As a new threat, the need for surveillance of C. auris is critical. This is particularly important for a cosmopolitan setting and global hub such as the United Arab Emirates (UAE) where continued introduction and emergence of resistant variant strains is a major concern. Methods: The United Arab Emirates has carried out a 12 years of antimicrobial resistance surveillance (2010-2021) across the country, spanning all seven Emirates. A retrospective analysis of C. auris emergence from 2018-2021 was undertaken, utilising the demographic and microbiological data collected via a unified WHONET platform for AMR surveillance. Results: Nine hundred eight non-duplicate C. auris isolates were reported from 2018-2021. An exponential upward trend of cases was found. Most isolates were isolated from urine, blood, skin and soft tissue, and the respiratory tract. UAE nationals nationals comprised 29% (n = 186 of 632) of all patients; the remainder were from 34 other nations. Almost all isolates were from inpatient settings (89.0%, n = 809). The cases show widespread distribution across all reporting sites in the country. C. auris resistance levels remained consistently high across all classes of antifungals used. C. auris in this population remains highly resistant to azoles (fluconazole, 72.6% in 2021) and amphotericin. Echinocandin resistance has now emerged and is increasing annually. There was no statistically significant difference in mortality between Candida auris and Candida spp. (non-auris) patients (p-value: 0.8179), however Candida auris patients had a higher intensive care unit (ICU) admission rate (p-value <0.0001) and longer hospital stay (p < 0.0001) compared to Candida spp. (non-auris) patients. Conclusion: The increasing trend of C. auris detection and associated multidrug resistant phenotypes in the UAE is alarming. Continued C. auris circulation in hospitals requires enhanced infection control measures to prevent continued dissemination.
An emerging Panton-Valentine leukocidin (PVL)-positive CC5-meticillin-resistant Staphylococcus aureus-IVc clone recovered from hospital and community settings over a 17-year period from 12 countries investigated by whole-genome sequencing
(2022-12) Senok, Abiola
Background: A novel Panton-Valentine leukocidin (PVL)-positive meticillin-resistant Staphylococcus aureus (MRSA) clonal complex (CC)5-MRSA-IVc ('Sri Lankan' clone) was recently described from Sri Lanka. Similar isolates caused a recent Irish hospital outbreak. Aim: To investigate the international dissemination and diversity of PVL-positive CC5-MRSA-IVc isolates from hospital and community settings using whole-genome sequencing (WGS). Methods: Core-genome single nucleotide polymorphism (cgSNP) analysis, core-genome multi-locus sequence typing (cgMLST) and microarray-based detection of antimicrobial-resistance and virulence genes were used to investigate PVL-positive CC5-MRSA-IVc (N = 214 including 46 'Sri Lankan' clone) from hospital and community settings in 12 countries over 17 years. Comparators included 29 PVL-positive and 23 PVL-negative CC5/ST5-MRSA-I/II/IVa/IVc/IVg/V. Results: Maximum-likelihood cgSNP analysis grouped 209/214 (97.7%) CC5-MRSA-IVc into Clade I; average of 110 cgSNPs between isolates. Clade III contained the five remaining CC5-MRSA-IVc; average of 92 cgSNPs between isolates. Clade II contained seven PVL-positive CC5-MRSA-IVa comparators, whereas the remaining 45 comparators formed an outlier group. Minimum-spanning cgMLST analysis revealed a comparably low average of 57 allelic differences between all CC5/ST5-MRSA-IVc. All 214 CC5/ST5-MRSA-IVc were identified as 'Sri Lankan' clone, predominantly spa type t002 (186/214) with low population diversity and harboured a similar range of virulence genes and variable antimicrobial-resistance genes. All 214 Sri Lankan clone isolates and Clade II comparators harboured a 9616-bp chromosomal PVL-encoding phage remnant, suggesting both arose from a PVL-positive meticillin-susceptible ancestor. Over half of Sri Lankan clone isolates were from infections (142/214), and where detailed metadata were available (168/214), most were community associated (85/168). Conclusions: Stable chromosomal retention of pvl may facilitate Sri-Lankan clone dissemination.
Epidemiology and antimicrobial resistance trends of Acinetobacter species in the United Arab Emirates: a retrospective analysis of 12 years of national AMR surveillance data
(2023-12) Senok, Abiola
Abstract: Introduction: Acinetobacter spp., in particular A. baumannii, are opportunistic pathogens linked to nosocomial pneumonia (particularly ventilator-associated pneumonia), central-line catheter-associated blood stream infections, meningitis, urinary tract infections, surgical-site infections, and other types of wound infections. A. baumannii is able to acquire or upregulate various resistance determinants, making it frequently multidrug-resistant, and contributing to increased mortality and morbidity. Data on the epidemiology, levels, and trends of antimicrobial resistance of Acinetobacter spp. in clinical settings is scarce in the Gulf Cooperation Council (GCC) and Middle East and North Africa (MENA) regions. Methods: A retrospective 12-year analysis of 17,564 non-duplicate diagnostic Acinetobacter spp. isolates from the United Arab Emirates (UAE) was conducted. Data was generated at 317 surveillance sites by routine patient care during 2010-2021, collected by trained personnel and reported by participating surveillance sites to the UAE National AMR Surveillance program. Data analysis was conducted with WHONET. Results: Species belonging to the A. calcoaceticus-baumannii complex were mostly reported (86.7%). They were most commonly isolated from urine (32.9%), sputum (29.0%), and soft tissue (25.1%). Resistance trends to antibiotics from different classes during the surveillance period showed a decreasing trend. Specifically, there was a significant decrease in resistance to imipenem, meropenem, and amikacin. Resistance was lowest among Acinetobacter species to both colistin and tigecycline. The percentages of multidrug-resistant (MDR) and possibly extensively drug-resistant (XDR) isolates was reduced by almost half between the beginning of the study in 2010 and its culmination in 2021. Carbapenem-resistant Acinetobacter spp. (CRAB) was associated with a higher mortality (RR: 5.7), a higher admission to ICU (RR 3.3), and an increased length of stay (LOS; 13 excess inpatient days per CRAB case), as compared to Carbapenem-susceptible Acinetobacter spp. Conclusion: Carbapenem-resistant Acinetobacter spp. are associated with poorer clinical outcomes, and higher associated costs, as compared to carbapenem-susceptible Acinetobacter spp. A decreasing trend of MDR Acinetobacter spp., as well as resistance to all antibiotic classes under surveillance was observed during 2010 to 2021. Further studies are needed to explore the reasons and underlying factors leading to this remarkable decrease of resistance over time.
Epidemiology of vancomycin-resistant enterococci in the United Arab Emirates: a retrospective analysis of 12 years of national AMR surveillance data
(2023) Senok, Abiola
Introduction: Enterococci are usually low pathogenic, but can cause invasive disease under certain circumstances, including urinary tract infections, bacteremia, endocarditis, and meningitis, and are associated with peritonitis and intra-abdominal abscesses. Increasing resistance of enterococci to glycopeptides and fluoroquinolones, and high-level resistance to aminoglycosides is a concern. National antimicrobial resistance (AMR) surveillance data for enterococci from the Middle East and North Africa (MENA) and the Gulf region is scarce. Methods: A retrospective 12-year analysis of N = 37,909 non-duplicate diagnostic Enterococcus spp. isolates from the United Arab Emirates (UAE) was conducted. Data was generated by routine patient care during 2010–2021, collected by trained personnel and reported by participating surveillance sites to the UAE National AMR Surveillance program. Data analysis was conducted with WHONET. Results: Enterococcus faecalis was the most commonly reported species (81.5%), followed by Enterococcus faecium (8.5%), and other enterococci species (4.8%). Phenotypically vancomycin-resistant enterococci (VRE) were found in 1.8% of Enterococcus spp. isolates. Prevalence of VRE (%VRE) was highest for E. faecium (8.1%), followed by E. faecalis (0.9%). A significant level of resistance to glycopeptides (%VRE) for these two species has been observed in the majority of observed years [E. faecalis (0–2.2%), 2010: 0%, 2021: 0.6%] and E. faecium (0–14.2%, 2010: 0%, 2021: 5.8%). Resistance to fluoroquinolones was between 17 and 29% (E. faecalis) and was higher for E. faecium (between 42 and 83%). VRE were associated with higher patient mortality (RR: 2.97), admission to intensive care units (RR: 2.25), and increased length of stay (six excess inpatient days per VRE case), as compared to vancomycin-susceptible Enterococcus spp. Frontiers in Public Health 01 frontiersin.o Thomsen et al. 10.3389/fpubh.2023.1275778 Discussion: Published data on Enterococcus infections, in particular VREinfections, in the UAE and MENA region is scarce. Our data demonstrates that VRE-enterococci are relatively rare in the UAE, however showing an increasing resistance trend for several clinically important antibiotic classes, causing a concern for the treatment of serious infections caused by enterococci. This study also demonstrates that VRE were associated with higher mortality, increased intensive care unit admission rates, and longer hospitalization, thus poorer clinical outcome and higher associated costs in the UAE. We recommend the expansion of current surveillance techniques (e.g., local VRE screening), stricter infection prevention and control strategies, and better stewardship interventions. Further studies on the molecular epidemiology of enterococci are needed.
Evolving trends among Pseudomonas aeruginosa: a 12-year retrospective study from the United Arab Emirates
(2023-11) Senok, Abiola
Abstract: Introduction: Pseudomonas is a group of ubiquitous non-fermenting Gram-negative bacteria (NFGNB). Of the several species associated with humans, Pseudomonas aeruginosa (PA) can acclimate to diverse environments. The global frequency of PA infections is rising and is complicated by this organism's high intrinsic and acquired resistance to several clinically relevant antibiotics. Data on the epidemiology, levels, and trends of antimicrobial resistance of PA in clinical settings in the MENA/GCC region is scarce. Methods: A retrospective 12-year analysis of 56,618 non-duplicate diagnostic Pseudomonas spp. from the United Arab Emirates (UAE) was conducted. Data was generated at 317 surveillance sites by routine patient care during 2010-2021, collected by trained personnel and reported by participating surveillance sites to the UAE National antimicrobial resistance (AMR) Surveillance program. Data analysis was conducted with WHONET (https://whonet.org/). Results: Among the total isolates (N = 56,618), the majority were PA (95.6%). Data on nationality revealed 44.1% were UAE nationals. Most isolates were from soft tissue (55.7%), followed by respiratory tract (26.7%). PA was more commonly found among inpatients than among outpatients, followed by ICUs. PA showed a horizontal trend for resistance to fluoroquinolones, 3rd- and 4th-generation cephalosporins, and decreasing trends of resistance for aminoglycosides and meropenem. The highest percentage of multidrug resistant (MDR) isolates was reported in 2011 at 35.6%. As an overall trend, the percentage of MDR, extensively drug-resistant (XDR), and possible pandrug-resistant (PDR) isolates generally declined over the study period. Carbapenem-resistant PA (CRPA) were associated with a higher mortality (RR: 2.7), increased admission to ICU (RR: 2.3), and increased length of stay (LOS) (12 excess inpatient days per case), as compared to carbapenem-susceptible PA (CSPA). Conclusion: The resistance trends in Pseudomonas species in the UAE indicated a decline in AMR and in percentages of Pseudomonas isolates with MDR and XDR profiles. The sustained Pseudomonas spp. circulation particularly in the hospital settings highlights the importance of surveillance techniques, infection control strategies, and stewardship to limit the continued dissemination. This data also shows that CRPA are associated with higher mortality, increased ICU admission rates, and a longer hospitalization, thus higher costs due to increased number of in-hospital and ICU days.
First Report of blaCTX-M-28 in Enterobacteriaceae Isolates in the United Arab Emirates
(2018) Senok, Abiola
Background: The CTX-M family of extended-spectrum beta lactamase (ESBL) enzymes is comprised of over 60 𝑏𝑙𝑎CTX-M gene variants with the predominance of 𝑏𝑙𝑎CTX-M-15 in many regions. In this report, we present the first description of 𝑏𝑙𝑎CTX-M-28 in the United Arab Emirates. Methods: Forty-five non-duplicate ESBL producing isolates identified in a secondary care facility in the United Arab Emirates from June to July 2016 were studied. Gene sequencing was performed and DNA sequences were annotated using the BLAST program to identify the gene subtypes. Results: The majority of the ESBL positive isolates were E. coli(𝑛/𝑁 = 39/45; 86.6%) followed by K. pneumoniae (𝑛=5) and K. oxytoca (𝑛=1). All isolates harboured 𝑏𝑙𝑎CTX-M and 𝑏𝑙𝑎TEM genes, 18 had 𝑏𝑙𝑎SHV, and 2 were 𝑏𝑙𝑎VIM positive. Thirty-seven isolates (82.2%) were positive for 𝑏𝑙𝑎CTX-M-28. Other 𝑏𝑙𝑎CTX-M genes identified include 𝑏𝑙𝑎CTX-M-167 (𝑛=2; isolates #1 and 26) and one each for 𝑏𝑙𝑎CTX-M-38, 𝑏𝑙𝑎CTX-M-163, and 𝑏𝑙𝑎CTX-M-198. No 𝑏𝑙𝑎CTX-M-15 was identified. The predominant 𝑏𝑙𝑎TEM subtype was 𝑏𝑙𝑎TEM-171 (𝑛=8) followed by one of each of 𝑏𝑙𝑎TEM-120, 𝑏𝑙𝑎TEM-163, and 𝑏𝑙𝑎TEM-206. The 𝑏𝑙𝑎SHV subtypes were 𝑏𝑙𝑎SHV-148 and 𝑏𝑙𝑎SHV-187. Conclusion: The findings indicate the first description of 𝑏𝑙𝑎CTX-M-28 in a setting where 𝑏𝑙𝑎CTX-M-15 was previously predominant.
Genotype-phenotype correlation identified a novel SARS-CoV-2 variant possibly linked to severe disease
(2021) Loney, Tom; Al Suwaidi, Hanan; Uddin, Mohammed; Senok, Abiola; Nowotny, Norbert; Alsheikh-Ali, Alawi; Tayoun, Ahmad Abou
Abstract: The geographic location and heterogeneous multi-ethnic population of Dubai (United Arab Emirates; UAE) provide a unique setting to explore the global molecular epidemiology of SARS-CoV-2 and relationship between different viral strains and disease severity. We systematically selected (i.e. every 100th individual in the central Dubai COVID-19 database) 256 patients by age, sex, disease severity and month to provide a representative sample of laboratory-confirmed COVID-19 patients (nasopharyngeal swab PCR positive) during the first wave of the UAE outbreak (January to June 2020). Sociodemographic and clinical data were extracted from medical records and full SARS-CoV-2 genome sequences extracted from nasopharyngeal swabs were analysed. Older age was significantly associated with COVID-19-associated hospital admission and mortality. Overweight/obese or diabetic patients were 3–4 times more likely to be admitted to hospital and intensive care unit (ICU). Sequencing data showed multiple independent viral introductions into the UAE from Europe, Iran and Asia (29 January–18 March), and these early strains seeded significant clustering consistent with almost exclusive community-based transmission between April and June 2020. Majority of sequenced strains (N = 60, 52%) were from the European cluster consistent with the higher infectivity rates associated with the D614G mutation carried by most strains in this cluster. A total of 986 mutations were identified in 115 genomes, 272 were unique (majority were missense, n = 134) and 20/272 mutations were novel. A missense (Q271R) and synonymous (R41R) mutation in the S and N proteins, respectively, were identified in 2/27 patients with severe COVID-19 but not in patients with mild or moderate disease (0/86; p = .05, Fisher's Exact Test). Both patients were women (51–64 years) with no significant underlying health conditions. The same two mutations were identified in a healthy 37-year-old Indian man who was hospitalized in India due to COVID-19. Our findings provide evidence for continued communitybased transmission of the European strains in the Dubai population and highlight new mutations that might be associated with severe disease in otherwise healthy adults.