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.
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