The goal of this study was to genotypically characterize extended-spectrum β-lactamase-producing Escherichia coli isolates from the western region of Saudi Arabia and to identify active antibiotics against these isolates using phenotypic and molecular modeling. In total, 211 ESBL-producing E. coli isolates recovered from heterogeneous clinical specimens were identified by MALDI-TOF. Thirty-two sequence types (STs) were identified from a multilocus sequence typing (MLST) analysis of ESBL-producing E. coli, including a novel ST (ST8162). The most common ST in the Saudi and expatriate population was ST131, followed by ST38. All the isolates were multidrug resistant (MDR), and >95% of the isolates were resistant to third-generation (ceftriaxone and ceftazidime) and fourth-generation (cefepime) cephalosporins. The ESBL-positive E. coli isolates primarily harbored the blaCTX-M and blaTEM genes. No resistance was observed against the carbapenem antibiotic group. All the ESBL-producing E. coli isolates were observed to be susceptible to a ceftazidime/avibactam combination. Molecular interaction analyses of the docked complexes revealed the amino acid residues crucial for the binding of antibiotics and inhibitors to the modeled CTX-M-15 enzyme. Importantly, avibactam displayed the most robust interaction with CTX-M-15 among the tested inhibitors in the docked state (∆G = −6.6 kcal/mol). The binding free energy values for clavulanate, tazobactam and sulbactam were determined to be −5.7, −5.9 and −5.2 kcal/mol, respectively. Overall, the study concludes that ‘ceftazidime along with avibactam’ should be carefully used as a treatment option against only carbapenem-resistant MDR ESBL-producing E. coli in this region.

Background: Enterococcus faecalis is a ubiquitous member of the gut microbiota and has emerged as a lifethreatening multidrug-resistant (MDR) nosocomial pathogen. The aim of this study was to survey the prevalence of multidrug-resistant and epidemiologically important strains of E. faecalis in the western region of Saudi Arabia using phenotypic and whole genome sequencing approaches. Methods: In total, 155 patients positive for E. faecalis infection were included in this study. The isolates were identified by MALDI-TOF, and screen for antimicrobial resistance using VITEK-2 system. Genome sequencing was performed with paired-end strategy using MiSeq platform. Results: Seventeen sequence types (STs) were identified through multilocus sequence typing (MLST) analysis of the E. faecalis genomes, including two novels STs (ST862 and ST863). The most common STs in the Saudi patients were ST179 and ST16 from clonal complex 16 (CC16). Around 96% (n = 149) isolates were MDR. The antibiotics quinupristin/dalfopristin, clindamycin, and erythromycin demonstrated almost no coverage, and high-level streptomycin, gentamycin, and ciprofloxacin demonstrated suboptimal coverage. Low resistance was observed against vancomycin, linezolid, and ampicillin. Moreover, 34 antimicrobial resistance genes and variants, and three families of insertion sequences were found in the E. faecalis genomes, which likely contributed to the observed antimicrobial resistance. Twenty-two virulence factors, which were mainly associated with biofilm formation, endocarditis, cell adherence, and colonization, were detected in the isolates. Conclusions: Diverse STs of E. faecalis, including strains associated with common nosocomial infections are circulating in the healthcare facility of Saudi Arabia and carried multi-drug resistance, which has important implications for infection control.

Since 2012, MERS-CoV has caused up to 2220 cases and 790 deaths in 27 countries with Saudi Arabia being the most affected country with~83.1% of the cases and~38.8% local death rate. Current serological assays such as microneutralization (MN), plaque reduction neutralization, immunofluorescence, protein microarray or pseudoparticle neutralization assays rely on handling of live MERS-CoV in high containment laboratories or need for expensive and special equipment and reagents and highly trained personnel which represent a technical hurdle for most laboratories in resource-limited MERS-CoV endemic countries. Here, we developed, compared and evaluated three different indirect ELISAs based on MERS-CoV nucleocapsid protein (N), spike (S) ectodomain (amino acids 1-1297) and S1 subunit (amino acids 1-725) and compared them with MN assay. The developed ELISAs were evaluated using large number of confirmed seropositive (79 samples) and seronegative (274 samples) MERS-CoV human serum samples. Both rS1-and rS-ELISAs maintained high sensitivity and specificity (≥90%) across a wider range of OD values compared to rN-ELISA. Moreover, rS1-and rS-based ELISAs showed better agreement and correlation with MN assay in contrast to rN-ELISA. Collectively, our data demonstrate that rS1-ELISA and rS-ELISA are more reliable than rN-ELISA and represent a suitable choice for seroepidemiological testing and surveillance in MERS-CoV endemic regions. Several MERS-CoV serological assays have been developed and https://doi.

ObjectivesTo analyze and evaluate the safety and cost-effectiveness of a gradually-implemented antimicrobial stewardship programs (ASP) in a tertiary care center.MethodsProspective data were collected from an ASP that was gradually introduced between April 2012 and December 2013 in 6 hospital departments, over successive periods of 3 months each. A multidisciplinary team supervised antibiotic use and regulated pharmacy dispensations of a list of restricted antimicrobials (RAs). Indicators were prospectively monitored and included hospital mortality as the safety indicator; incidence of multi-drug resistance (MDR) infections as the effectiveness indicator, RA cost savings as the cost-effectiveness indicator and RA consumption indicated the process implementation.ResultsBetween 2012 and 2014, dispensations of RAs decreased by 67% and prescriptions by 75%; no increase in mortality rate was observed. Microbiologically, there was a decreasing trend of incidence across all monitored infections, but this was only significant for Acinetobacter baumannii (p=0.007). Cost analysis showed a decrease in expenditure for RAs, with an average monthly saving of up to 326,020USD.ConclusionsStepwise implementation of ASPs is a safe and cost-effective strategy for improving antibiotic prescribing practice and to reduce multi-drug resistance.

Introduction: The World Health Organization's persistent reporting of global outbreaks of influenza A viruses, including the 2009 pandemic swine A H1N1 strain (H1N1pdm09), justified the targeted surveillance of pilgrims during their annual congregation that pools more than two million people from around 165 nations in a confined area of Makkah city in the Kingdom of Saudi Arabia (KSA). Methodology: A total of 1,600 pilgrims were included in the targeted surveillance of influenza A and the 2009 pandemic swine H1N1 strain in the Hajj (pilgrimage) season of 2010. Each pilgrim responded to a demographic and health questionnaire. Collected oropharyngeal swabs were analyzed by real-time PCR for influenza A viruses, and positive samples were further analyzed for the presence of H1N1pdm09. Fisher's exact test was applied in the analysis of the significance of the distribution of influenza-positive pilgrims according to demographic characters. Results: A total of 120 pilgrims (7.5%) tested positive for influenza A viruses by real-time PCR. Nine out of the 120 influenza-A-positive pilgrims (7.5%) were positive for H1N1pdm09. Demographics played a significant role in those pilgrims who tested positive for influenza A. Conclusions: The detection of H1N1pdm09 in pilgrims at their port of entry to the KSA was alarming, due to the high potential of transboundary transmission. This situation necessitates the implementation of specific prevention and control programs to limit infection by influenza A viruses.

The objective of this study was to assess the validity of the new dengue classification proposed by the World Health Organization (WHO) in 2009 and to develop pragmatic guidelines for case triage and management. This retrospective study involved 357 laboratory-confirmed cases of dengue infection diagnosed at King Abdulaziz University Hospital, Jeddah, Saudi Arabia over a 4-year period from 2014 to 2017. The sensitivity of the new classification for identifying severe cases was limited (65%) but higher than the old one (30%). It had a higher sensitivity for identifying patients who needed advanced healthcare compared to the old one (72% versus 32%, respectively). We propose adding decompensation of chronic diseases and thrombocytopenia-related bleeding to the category of severe dengue in the new classification. This modification improves sensitivity from 72% to 98% for identifying patients who need advanced healthcare without altering specificity (97%). It also improves sensitivity in predicting severe outcomes from 32% to 88%. In conclusion, the new classification had a low sensitivity for identifying patients needing advanced care and for predicting morbidity and mortality. We propose to include decompensation of chronic diseases and thrombocytopenia-related bleeding to the category of severe dengue in the new classification to improve the sensitivity of predicting cases requiring advanced care.

Therefore, the identification and management of important contributory factors by identifying the regulation of adipocyte differentiation leading to a chronic condition like adipogenesis and insulin resistance resulting in obesity is an urgent requirement globally for human health.

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