Evolving trends among Pseudomonas aeruginosa: a 12-year retrospective study from the United Arab Emirates.

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.

Association of the gut microbiota with clinical variables in obese and lean Emirati subjects.

Background: Growing evidence supports the role of gut microbiota in obesity, yet exact associations remain largely unknown. Specifically, very little is known about this association in the Emirati population. Methods: We explored differences in gut microbiota composition, particularly the Firmicutes/Bacteroidetes (F/B) ratio, between 43 obese and 31 lean adult Emirate counterparts, and its association with obesity markers, by using V3-V4 regions of 16 S ribosomal RNA gene sequencing data. Furthermore, we collected anthropometric and biochemical data. Results: The two major phyla in obese and lean groups were Firmicutes and Bacteroidetes. We observed a significantly lower alpha diversity (Shannon index) in obese subjects and a significant difference in beta diversity and phylum and genus levels between the two groups. The obese group had higher abundances of Verrucomicrobia and Saccharibacteira and lower abundances of Lentisphaerae. Acidaminococcus and Lachnospira were more abundant in obese subjects and positively correlated with adiposity markers. No correlations were found between the gut microbiota and biochemical variables, such as fasting blood sugar, total cholesterol, HDL cholesterol, LDL cholesterol, and triglycerides. Conclusion: We reveal significant differences in the gut microbiota between obese and lean adult Emiratis and an association between certain microbial genera of the gut microbiota and obesity. A better understanding of the interactions between gut microbes, diet, lifestyle, and health is warranted.

Characterization of physicochemical parameters and bacterial diversity of composted organic food wastes in Dubai.

Composting favours recycling organic waste and producing an end product with high bioenergy potential and significant nutritional value for the soil. Analysing composted organic waste prepared in Dubai, a region with a desertic climate and a unique environment is essential since environmental conditions can greatly affect the physicochemical and biological soil properties and no studies in the Gulf region have been published yet on that process. This study analysed twelve different compost samples prepared in well ventilated wooden chambers, using home-generated organic wastes following the hot aerobic composting method for a duration of three months. The physicochemical parameters, measured at the end of the study, revealed that organic matter, electrical conductivity and pH were within the standard ranges while moisture content was low. Concerning macronutrients, most of the samples were within the standard range for carbon, potassium and sodium, while they were poor in phosphorous and nitrogen. Metagenomic analysis with Illumina MiSeq revealed the abundance of Firmicutes (30.35%), followed by Bacteroidota (26.69%), Proteobacteria (21.47%), and Actinobacteriota (11.17%). The phylum Planctomycetota, solely detected in compost and known to have a significant impact on soil ecosystem and decomposition of organic matter, was reported at a relatively significant level (2.35%). The Clostridia class, efficient in degrading cellulose, was described at high levels compared to other studies. The composting project succeeded in generating a healthy soil but lengthening the duration will allow the samples to fully decompose and therefore increase the total available nitrogen and phosphorus to meet the criteria of a typical mature compost. Various microbial consortia helped in the decomposition process. The qualitative information collected in this study will help in improving the composting technology to favour its utilization by a larger public in the Gulf region.

Emergence of highly resistant Candida auris in the United Arab Emirates: a retrospective analysis of evolving national trends.

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.

Elucidating the effect of iron acquisition systems in Klebsiella pneumoniae on susceptibility to the novel siderophore-cephalosporin cefiderocol.

BACKGROUND: Cefiderocol (CFDC) is a novel siderophore-cephalosporin, effective against multidrug-resistant Gram-negative bacteria. As it has a siderophore side chain, it can utilize iron acquisition systems for penetration of the bacterial outer membrane. We aimed to elucidate the role of siderophores and iron uptake receptors in defining Klebsiella pneumoniae susceptibility to CFDC. METHODS: Initially, 103 K. pneumoniae strains were characterized for susceptibility to different antibiotics including CFDC. CFDC minimum inhibitory concentrations (MIC) were determined in iron-depleted and iron-enriched conditions. Iron uptake genes including siderophores, their receptors, ferric citrate (fecA) and iron uptake (kfu) receptors were detected by PCR in all the strains. For 10 selected strains, gene expression was tested in iron-depleted media with or without CFDC treatment and compared to expression in iron-enriched conditions. RESULTS: CFDC exhibited 96.1% susceptibility, being superior to all the other antibiotics (MIC50: 0.5 and MIC90: 4 µg/ml). Only three strains (2.9%) were intermediately susceptible and a pandrug resistant strain (0.97%) was resistant to CFDC (MIC: 8 and 256 µg/ml, respectively). The presence of kfu and fecA had a significant impact on CFDC MIC, especially when co-produced, and if coupled with yersiniabactin receptor (fyuA). CFDC MICs were negatively correlated with enterobactin receptor (fepA) expression and positively correlated with expression of kfu and fecA. Thus, fepA was associated with increased susceptibility to CFDC, while kfu and fecA were associated with reduced susceptibility to CFDC. CFDC MICs increased significantly in iron-enriched media, with reduced expression of siderophore receptors, hence, causing less drug uptake. CONCLUSION: Iron acquisition systems have a significant impact on CFDC activity, and their altered expression is a factor leading to reduced susceptibility. Iron concentration is also a major player affecting CFDC susceptibility; therefore, it is essential to explore possible ways to improve the drug activity to facilitate its use to treat infections in iron-rich sites.

The Association between Peptide Hormones with Obesity and Insulin Resistance Markers in Lean and Obese Individuals in the United Arab Emirates.

Peptide hormones play a crucial role in body weight and glucose homeostasis. In this study, we aimed to explore this association and recruited 43 obese and 31 age- and sex-matched lean participants. We assessed their body mass index (BMI), waist circumference (WC), waist-to-height ratio (WtHR), percentage body fat (PBF), fasting blood levels of peptide hormones (GLP-1, GLP-2, insulin, leptin, ghrelin, CCK, and PYY), fasting blood sugar (FBS), and Homeostatic Model Assessment of Insulin Resistance (HOMA-IR). We tested the associations between peptide hormones and markers of obesity and insulin resistance (IR) by using the Independent-Samples t-test and Mann-Whitney U test, partial correlation, and logistic regression. FBS, insulin, HOMA-IR, GLP-1, GLP-2, and leptin were significantly higher in the obese group; ghrelin and CCK were significantly higher in lean participants, and no difference was seen for PYY. Controlling for BMI, GLP-1 was positively correlated with WtHR, while ghrelin was inversely correlated with WtHR. GLP-1 was correlated with HOMA-IR. GLP-1 was associated with obesity and IR markers in the regression model. Our results show that obese and lean adults display significant differences in plasma peptide hormone levels. GLP-1 levels were independently associated with markers of obesity and IR. Restoring the appetite hormone balance in obesity may represent a potential therapeutic target.

Bactericidal effects and stability of LL-37 and CAMA in the presence of human lung epithelial cells.

Cationic antimicrobial peptides (CAMPs) are important actors in host innate immunity and represent a promising alternative to combat antibiotic resistance. Here, the bactericidal activity of two CAMPs (LL-37 and CAMA) was evaluated against Pseudomonas aeruginosa (PA) in the presence of IB3-1 cells, a cell line derived from patients with cystic fibrosis. The two CAMPs exerted different effects on PA survival depending on the timing of their administration. We observed a greater bactericidal effect when IB3-1 cells were pretreated with sub-minimum bactericidal concentrations (Sub-MBCs) of the CAMPs prior to infection. These findings suggest that CAMPs induce the production of factors by IB3-1 cells that improve their bactericidal action. However, we observed no bactericidal effect when supra-minimum bactericidal concentrations (Supra-MBCs) of the CAMPs were added to IB3-1 cells at the same time or after infection. Western-blot analysis showed a large decrease in LL-37 levels in supernatants of infected IB3-1 cells and an increase in LL-37 binding to these cells after LL-37 administration. LL-37 induced a weak inflammatory response in the cells without being toxic. In conclusion, our findings suggest a potential prophylactic action of CAMPs. The bactericidal effects were low when the CAMPs were added after cell infection, likely due to degradation of CAMPs by bacterial or epithelial cell proteases and/or due to adherence of CAMPs to cells becoming less available for direct bacterial killing.

Human Milk Microbiota and Oligosaccharides: A Glimpse into Benefits, Diversity, and Correlations.

Human milk represents a cornerstone for growth and development of infants, with extensive array of benefits. In addition to exceptionally nutritive and bioactive components, human milk encompasses a complex community of signature bacteria that helps establish infant gut microbiota, contributes to maturation of infant immune system, and competitively interferes with pathogens. Among bioactive constituents of milk, human milk oligosaccharides (HMOs) are particularly significant. These are non-digestible carbohydrates forming the third largest solid component in human milk. Valuable effects of HMOs include shaping intestinal microbiota, imparting antimicrobial effects, developing intestinal barrier, and modulating immune response. Moreover, recent investigations suggest correlations between HMOs and milk microbiota, with complex links possibly existing with environmental factors, genetics, geographical location, and other factors. In this review, and from a physiological and health implications perspective, milk benefits for newborns and mothers are highlighted. From a microbiological perspective, a focused insight into milk microbiota, including origins, diversity, benefits, and effect of maternal diet is presented. From a metabolic perspective, biochemical, physiological, and genetic significance of HMOs, and their probable relations to milk microbiota, are addressed. Ongoing research into mechanistic processes through which the rich biological assets of milk promote development, shaping of microbiota, and immunity is tackled.

Expression and Roles of Antimicrobial Peptides in Innate Defense of Airway Mucosa: Potential Implication in Cystic Fibrosis.

The treatment of respiratory infections is associated with the dissemination of antibiotic resistance in the community and clinical settings. Development of new antibiotics is notoriously costly and slow; therefore, alternative strategies are needed. Antimicrobial peptides (AMPs), the central effector molecules of the immune system, are being considered as alternatives to conventional antibiotics. Most AMPs are epithelium-derived and play a key role in host defense at mucosal surfaces. They are classified on the basis of their structure and amino acid motifs. These peptides display a range of activities, including not only direct antimicrobial activity, but also immunomodulation and wound repair. In the lung, airway epithelial cells and neutrophils, in particular, contribute to AMP synthesis. The relevance of AMPs for host defense against infection has been demonstrated in animal models and is supported by observations in patient studies, showing altered expression and/or unfavorable circumstances for their action in a variety of lung diseases. Of note, AMPs are active against bacterial strains that are resistant to conventional antibiotics, including multidrug-resistant bacteria. Several strategies have been proposed to use these peptides in the treatment of infections, including direct administration of AMPs. In this review, we focus on studies related to direct bactericidal effects of AMPs and their potential clinical applications with a particular focus on cystic fibrosis.

Assessment of the performance of CHROMagar KPC and Xpert Carba-R assay for the detection of carbapenem-resistant bacteria in rectal swabs: First comparative study from Abu Dhabi, United Arab Emirates.

OBJECTIVES: The objective of this study was to evaluate the performance of CHROMagar™ KPC compared with Xpert® Carba-R assay for the detection of carbapenem-resistant bacterial isolates from rectal swabs. METHODS: Rectal swabs were obtained from patients admitted to Cleveland Clinic Abu Dhabi (United Arab Emirates) over a period of 7 months and were screened for carbapenem resistance by either culture on CHROMagar KPC or carbapenemase production using the Xpert Carba-R molecular method. Further testing for carbapenem susceptibility of isolates recovered from CHROMagar KPC was performed using VITEK®2. RESULTS: A total of 1813 rectal swabs were screened, of which 61 (3.4%) were positive for carbapenem resistance by either one or both methods. Both methods were equally efficient in detecting carbapenem resistance in 37/61 swabs (60.7%), mostly positive for Klebsiella pneumoniae (22 isolates), of which 40.9% (9/22) carried blaOXA-48-like and blaNDM. Xpert Carba-R assay detected 12 additional swabs with negative CHROMagar KPC culture and revealed additional carbapenemase-producing organisms carrying blaOXA-48-like and/or blaNDM. CHROMagar KPC recovered organisms in nine swabs not detected by the genotypic method, 44.4% of which were K. pneumoniae. Three swabs yielded false-positive results (carbapenem-susceptible organisms) by both methods. Sensitivity and specificity were, respectively, 75.4% and 99.8% for CHROMagar KPC and 80% and 99.8% for Xpert Carba-R. CONCLUSION: This comparative study of CHROMagar KPC versus Xpert Carba-R in rectal swabs showed a slightly higher sensitivity for the PCR-based method. Whilst CHROMagar KPC provides a less expensive screening method, Xpert Carba-R may be more accurate and faster.

Clonal emergence of Klebsiella pneumoniae ST14 co-producing OXA-48-type and NDM carbapenemases with high rate of colistin resistance in Dubai, United Arab Emirates.

Few studies have addressed the molecular epidemiology of carbapenem-resistant Enterobacteriaceae (CRE) isolates in the Arabian Peninsula, and such investigations have been missing from Dubai, a major economical, tourism and medical centre of the region. The antibiotic susceptibility, the carbapenemase type produced, and the clonality of 89 CRE strains isolated in five major Dubai hospitals in June 2015 to June 2016 were determined. Thirty-three percent of the collection of 70 Klebsiella pneumoniae, 13 Escherichia coli and 6 other Enterobacteriaceae were extremely drug resistant, 27% were resistant to colistin, and 4.5% (4 K. pneumoniae isolates) were resistant to all antibiotics tested. The colistin resistance rate in K. pneumoniae was 31.4%. None of the isolates carried mobile colistin resistance genes. Seventy-seven isolates produced carbapenemase: 53.3% OXA-48-like, 24.7% NDM and 22.1% both OXA-48-like and NDM, respectively. Pulsed-field gel electrophoresis clustered 50% of K. pneumoniae into a 35-membered group, which showed significant association with double carbapenemase production, with extreme drug resistance, and with being isolated from Emirati patients. Members of the cluster belonged to sequence type ST14. The rate of colistin resistance in K. pneumoniae ST14 was 37.1% vs. 27.1% of K. pneumoniae isolates outside of the cluster. Two of the panresistant K. pneumoniae isolates also belonged to ST14, whereas the other two were ST15 and ST231, respectively. In conclusion, beyond the overall high colistin resistance rate in CRE, the emergence of a highly resistant clone of K. pneumoniae ST14 in all Dubai hospitals investigated is a serious problem requiring immediate attention.

Heterogeneity of Carbapenem Resistance Mechanisms Among Gram-Negative Pathogens in Lebanon: Results of the First Cross-Sectional Countrywide Study.

Carbapenem-resistant Gram-negative pathogens have progressively disseminated to different countries worldwide, presenting a serious public health concern. The aims of this study were to determine the prevalence of carbapenem resistance in Gram-negative bacteria in Lebanon, to elucidate molecular mechanisms, and to identify genetic relatedness of incriminated strains. Carbapenem nonsusceptible Enterobacteriaceae, Acinetobacter baumannii, and Pseudomonas were collected from 11 Lebanese hospitals in 2012. Antimicrobial susceptibility was assessed with phenotypic tests, genes encoding carbapenemases were screened via PCR-sequencing, and genetic relatedness was examined by PGFE and ERIC-PCR. A total of 398 nonrepetitive carbapenem nonsusceptible isolates were studied, of which 44 were Enterobacteriaceae, 142 were A. baumannii, and 212 were Pseudomonas. Among Enterobacteriaceae, 70.4% carried blaOXA-48-like gene on IncL/M-type plasmids, while acquired AmpC cephalosporinases, extended-spectrum-ß-lactamases, and efflux-pump were additional contributors to carbapenem resistance. Among A. baumannii, 90% produced OXA-23 and GES-11 and carried insertion sequence ISAba1 upstream and adjacent to blaOXA-23 and blaAcinetobacter-derived cephalosporinases. Among Pseudomonas, 16% harbored VIM-2, 4.2% IMP-2, and 1.4% IMP-1 metallo-ß-lactamases. Fingerprint analysis indicated that the spread of OXA-48-like carbapenemases was mostly mediated by horizontal transfer, while OXA-23 and GES-11 diffusion in A. baumannii and VIM-2 diffusion in P. aeruginosa were primarily due to clonal dissemination. This study is the first nationwide investigation of carbapenem resistance in Lebanon, showing low level of resistance in Enterobacteriaceae, and higher levels in A. baumannii and Pseudomonas. With current changes in the region, continuous surveillance of carbapenem resistance is crucial.

SURVEILLANCE of CARBAPENEM NON-SUSCEPTIBLE GRAM NEGATIVE STRAINS and CHARACTERIZATION of CARBAPENEMASES of CLASSES A, B and D in a LEBANESE HOSPITAL.

The production of carbapenem-hydrolyzing enzymes has been recognized as one of the most currently relevant resistance mechanisms in gram negative bacterial isolates, and is being detected in various countries. In Lebanon, carbapenem resistance was studied among gram negative pathogens collected from a university hospital from January to June of years 2011 and 2012. All isolates were subjected to phenotypic tests including antibiotic susceptibility, cloxacillin effect, modified Hodge test, and Etest for metallo-ß-lactamase detection. They were also subjected to genotyping by PCR sequencing to characterize ß-lactamases. Between January and June 2011, 48 carbapenem non-susceptible strains were collected. Of these, one Klebsiella pneumoniae harbored OXA-48 and insertion sequence IS 1999; four Acinetobacter baumanni harbored simultaneously OXA-23 and GES-11, and three Pseudomonas harbored VIM-2 carbapenemase. Between January and June 2012, 100 carbapenem non-susceptible strains were collected. Of these, one K. pneumoniae harbored simultaneously OXA-48, IS 1999, and an acquired AmpC of the ACC group; four Serratia marcescens harbored OXA-48, while among eight A. baumannii, one strain co-harbored OXA-23 and GES-11, six harbored OXA-23 and one OXA-24. Fifteen P, aeruginosa and two Pseudomonas species harbored VIM-2; two P. aeruginosa strains produced IMP-1 and two others IMP-2. This epidemiological survey demonstrates the presence of carbapenemases of Ambler classes A, B, and D in a Lebanese hospital and indicates increase in the number and variety of such enzymes.