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Background It had been more than 5 years since the first case of Middle East Respiratory Syndrome coronavirus infection (MERS-CoV) was recorded, but no specific treatment has been investigated in randomized clinical trials. Results from in vitro and animal studies suggest that a combination of lopinavir/ritonavir and interferon-β1b (IFN-β1b) may be effective against MERS-CoV. The aim of this study is to investigate the efficacy of treatment with a combination of lopinavir/ritonavir and recombinant IFN-β1b provided with standard supportive care, compared to treatment with placebo provided with standard supportive care in patients with laboratory-confirmed MERS requiring hospital admission. Methods The protocol is prepared in accordance with the SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) guidelines. Hospitalized adult patients with laboratory-confirmed MERS will be enrolled in this recursive, two-stage, group sequential, multicenter, placebo-controlled, double-blind randomized controlled trial. The trial is initially designed to include 2 two-stage components. The first two-stage component is designed to adjust sample size and determine futility stopping, but not efficacy stopping. The second two-stage component is designed to determine efficacy stopping and possibly readjustment of sample size. The primary outcome is 90-day mortality. Discussion This will be the first randomized controlled trial of a potential treatment for MERS. The study is sponsored by King Abdullah International Medical Research Center, Riyadh, Saudi Arabia. Enrollment for this study began in November 2016, and has enrolled thirteen patients as of Jan 24-2018. Trial registration ClinicalTrials.gov, ID: NCT02845843 . Registered on 27 July 2016.

The MIRACLE trial (MERS-CoV Infection tReated with A Combination of Lopinavir/ritonavir and intErferon-β1b) investigates the efficacy of a combination therapy of lopinavir/ritonavir and recombinant interferon-β1b provided with standard supportive care, compared to placebo provided with standard supportive care, in hospitalized patients with laboratory-confirmed MERS. The MIRACLE trial is designed as a recursive, two-stage, group sequential, multicenter, placebo-controlled, double-blind randomized controlled trial. The aim of this article is to describe the statistical analysis plan for the MIRACLE trial. The primary outcome is 90-day mortality. The primary analysis will follow the intention-to-treat principle. The MIRACLE trial is the first randomized controlled trial for MERS treatment. Trial registration ClinicalTrials.gov, NCT02845843 . Registered on 27 July 2016.

Background Despite being largely preventable, surgical site infections (SSIs) are still one of the most frequent healthcare-associated infections. The presence of resistant pathogens can further augment their clinical and economic impacts. The objective was to estimate the distribution and resistance in SSI pathogens in Saudi Arabia and to compare them to the US National Healthcare Safety Network (NHSN) hospitals. Methods Targeted SSI surveillance was prospectively conducted on several surgical procedures done between 2007 and 2016 in four hospitals of Ministry of National Guard Health Affairs. Definitions and methodology of SSI and bacterial resistance were based on NHSN. Results A total 492 pathogens causing 403 SSI events were included. The most frequent pathogens were Staphylococcus aureus (22.8%), Pseudomonas aeruginosa (20.1%), Klebsiella spp. (12.2%), and Escherichia coli (12.2%), with marked variability between surgeries. Approximately 30.3% of Staphylococcus aureus was methicillin-resistant (MRSA), 13.0% of Enterococcus spp. was vancomycin-resistant (VRE), and 5.5% of Enterobacteriaceae were carbapenem resistant (CRE). The highest multidrug-resistant (MDR) GNPs were Acinetobacter spp. (58.3%), Klebsiella spp. (20.4%) and Escherichia coli (16.3%). MRSA was significantly less frequent while cephalosporin-resistant Klebsiella spp., MDR Klebsiella spp., and MDR Escherichia coli were significantly more frequent in our hospitals compared with NHSN hospitals. Conclusion GNPs in a tertiary care setting in Saudi Arabia are responsible for more than 60% of SSI with more resistant patterns than Western countries. This information may be critical to secure resources and ensure support for caregivers and healthcare leaders in implementing antimicrobial stewardship programs and evidence-based SSI preventive practices.

Background Klebsiella pneumoniae is a major bacterial and opportunistic human pathogen, increasingly recognized as a healthcare burden globally. The convergence of resistance and virulence in K. pneumoniae strains has led to the formation of hypervirulent and multidrug-resistant strains with dual risk, limiting treatment options. K. pneumoniae clones are known to emerge locally and spread globally. Therefore, an understanding of the dynamics and evolution of the emerging strains in hospitals is warranted to prevent future outbreaks. Methods In this study, we conducted an in-depth genomic analysis on a large-scale collection of 328 multidrug-resistant (MDR) K. pneumoniae strains recovered from 239 patients from a single major hospital in the western coastal city of Jeddah in Saudi Arabia from 2014 through 2022. We employed a broad range of phylogenetic and phylodynamic methods to understand the evolution of the predominant clones on epidemiological time scales, virulence and resistance determinants, and their dynamics. We also integrated the genomic data with detailed electronic health record (EHR) data for the patients to understand the clinical implications of the resistance and virulence of different strains. Results We discovered a diverse population underlying the infections, with most strains belonging to Clonal Complex 14 (CC14) exhibiting dominance. Specifically, we observed the emergence and continuous expansion of strains belonging to the dominant ST2096 in the CC14 clade across hospital wards in recent years. These strains acquired resistance mutations against colistin and extended spectrum β-lactamase (ESBL) and carbapenemase genes, namely bla OXA-48 and bla OXA-232 , located on three distinct plasmids, on epidemiological time scales. Strains of ST2096 exhibited a high virulence level with the presence of the siderophore aerobactin ( iuc ) locus situated on the same mosaic plasmid as the ESBL gene. Integration of ST2096 with EHR data confirmed the significant link between colonization by ST2096 and the diagnosis of sepsis and elevated in-hospital mortality ( p- value < 0.05). Conclusions Overall, these results demonstrate the clinical significance of ST2096 clones and illustrate the rapid evolution of an emerging hypervirulent and MDR K. pneumoniae in a clinical setting.

Mycobacterial avium complex (MAC) is one of the non-tuberculous mycobacterium (NTM) that is known to cause pulmonary disease (PD). MAC PD is diagnosed by fulfilling all of the following: presence of respiratory symptoms, imaging studies compatible with pulmonary disease, and isolation of the mycobacterium from either sputum or bronchial wash in symptomatic patients (isolation of at least two sputum specimens or at least one bronchial wash specimen). A mutation in the solute carrier family 11, member 1 (SLC11A1) gene has been associated with Mycobacteria infections, including MAC. Herein, we present a case of a young female diagnosed with pulmonary MAC who was found later to have an SLC11A1 genetic mutation.

ObjectivesThe present study was conducted to estimate the seroprevalence of antibody to pertussis toxin among adult populations in western Saudi Arabia.DesignA cross-sectional study.SettingKing Abdulaziz Medical City, Jeddah, western Saudi Arabia. A tertiary care teaching hospital.ParticipantsA total of 1200 participants (400 healthcare workers, 400 military recruits and 400 blood donors) were included. The majority were male (79.3%), and the mean (±SD) age was 27.2 (±6.7) years old.InterventionsThe study included the analysis of serum blood samples using commercial ELISA. A consecutive sampling technique was applied.Primary outcome measuresSeropositivity of antipertussis toxin immunoglobulin G (anti-PT IgG) ≥62.5 IU/mL.ResultsAntibody titres ≥62.5 IU/mL, indicating exposure to Bordetella pertussis infection within the last year, were identified in 12.0% (95% CI 10.2% to 14.0%) of the participants. Titres ≥125 IU/mL, suggesting recent infection, were detected in 3.5% (95% CI 2.5% to 4.7%). Seroprevalence of positive IgG antibody titres (≥62.5 IU/mL) was highest among the healthcare workers (HCWs) (14%), then the military recruits (13.5%) and blood donors (8.5%; p=0.03). The multivariate regression analysis showed association between participants group (HCWs and military), male gender and younger age (<25 years old) and higher antibody to pertussis toxin.ConclusionsHigh pertussis seropositivity was associated with participants’ occupation (ie, healthcare workers and military recruits), and anti-PT IgG titre was negatively correlated with age. A substantial deficiency in pertussis reporting in Saudi Arabia has been suggested, with potential increased risk to the most vulnerable populations (ie, infants and elderly). Enhancing the booster dose of pertussis vaccine for adolescents and adults is crucial to minimise the burden of pertussis.

Nosocomial infections caused by multi-drug resistant are a global public health threat that ought to be promptly identified, reported, and addressed accurately. Many carbapenem-resistant -associated genes have been identified in Saudi Arabia but not the endemic carbapenemases (KPCs), which are encoded by genes. KPCs are known for their exceptional spreading potential. We collected  = 286 multi-drug resistant (MDR) isolates as part of screening for resistant patterns from a tertiary hospital in Saudi Arabia between 2014 and 2018. Antimicrobial susceptibility testing was carried out using both VITEK II and the broth microdilution of all collected isolates. Detection of resistance-conferring genes was carried out using Illumina whole-genome shotgun sequencing and PacBio SMRT sequencing protocols. A Carbapenem-resistant (CRE) subsp. strain was identified as a novel ST-3510 carrying a carbapenemase encoding gene. The isolate, designated as NGKPC-421, was obtained from shotgun Whole Genome Sequencing (WGS) surveillance of 286 MDR . clinical isolates. The NGKPC-421 isolate was collected from a septic patient in late 2017 and was initially misidentified as . The sequencing and assembly of the NGKPC-421 genome resulted in the identification of a putative ~ 39.4 kb IncX6 plasmid harboring a gene, flanked by transposable elements (IS -IS ). This is the first identification of a KPC-2-producing CRE in the Gulf region. The impact on this finding is of major concern to the public health in Saudi Arabia, considering that it is the religious epicenter with a continuous mass influx of pilgrims from across the world. Our study strongly highlights the importance of implementing rapid sequencing-based technologies in clinical microbiology for precise taxonomic classification and monitoring of antimicrobial resistance patterns.

 The aim of the study is to estimate the prevalence rate of carbapenem-resistant Enterobacteriaceae (CRE) and to determine the types of carbapenemase genes present in patients admitted to King Abdulaziz Medical City (KAMC-J) and King Abdulaziz University Hospital (KAUH), both in Jeddah, Saudi Arabia.  A total of 180 isolates were analyzed which were included on the basis of retrospective chart review of patients from KAMC-J and KAUH between 1 April 2017 to 30 March 2019. The prevalence of carbapenemase genes was evaluated by Xpert® Carba-R (Cepheid, Sunnyvale, CA, USA). We assessed the CRE prevalence and described their susceptibility to antimicrobial agents based on antibiogram reports.  Results:   showed a higher frequency of OXA-48 (79%) than NDM (11.7%) genes (p=0.007). The CRE prevalence in KAUH was 8% in 2017 and increased to 13% in 2018. In KAMC-J, the prevalence was 57% in 2018 and 61% in 2019. was found to be the most frequently isolated causative organism followed by   The  OXA-48 (76.1%) gene was predominant among overall isolates followed by NDM (13.9%); both genes coexisted in 6.1% of the isolates.  During the study period, the prevalence of CRE considerably rose in the two tertiary care institutions from western Saudi Arabia. In the CRE isolates, OXA-48 was discovered to be the most common gene. We recommend an antimicrobial resistance surveillance system to detect the emergence of resistant genes through use of new rapid diagnostic tests and monitor antimicrobial use in order to improve clinical outcomes of CRE infections given the severity of infection associated with the CRE isolates as well as the limited treatment options available.

Introduction Influenza infection poses a significant public health threat. The core for disease prevention and control relies on strengthened surveillance activities, particularly in Saudi Arabia, the country that hosts the largest annual mass gathering event worldwide. This study aimed to assess the molecular and seasonal pattern of influenza virus subtypes in western Saudi Arabia to inform policy decisions on influenza vaccine. Methods This cross-sectional study was conducted at King Abdulaziz Medical City, western Saudi Arabia. Medical records and surveillance database of laboratory-confirmed influenza cases were reviewed from October 2015 to 2019. A panel of real-time polymerase chain reactions was performed to detect influenza A and B. Extracted RNA from a subset of positive samples was used to determine influenza A subtypes and influenza B lineages. Results This study included a total of 1928 patients with laboratory-confirmed influenza infections. Influenza peaks were observed in October each season, with variant predominant strains. Influenza virus subtypes co-circulate with no reports of co-infection. Influenza A(H3N2) was reported in 42% of the cases, then influenza B (30.7%) and influenza A(H1N1)pdm09 (27.3%). Healthcare workers represented 9.4% of the cases. One-third of the cases (30.4%) were admitted to the hospital with a median admission duration of 4 days. The influenza B viruses were subtyped in 218 cases. Victoria lineage was predominant (64.1%) in 2015 and 2016; however, Yamagata was predominant in the next two consecutive seasons (94.4% and 85.4%, respectively). Conclusion The burden due to influenza B may be underestimated with an observed vaccine mismatch. A quadrivalent influenza vaccine is recommended to reduce the health impact associated with influenza B infections. Molecular surveillance of the influenza viruses should be enhanced continuously for a better understanding of the influenza activity and assessment of vaccine effectiveness.

Background Studying temporal changes in resistant pathogens causing healthcare-associated infections (HAIs) is crucial in improving local antimicrobial and infection control practices. The objective was to describe ten-year trends of resistance in pathogens causing HAIs in a tertiary care setting in Saudi Arabia and to compare such trends with those of US National Health Surveillance Network (NHSN). Methods Pooled analysis of surveillance data that were prospectively collected between 2007 and 2016 in four hospitals of Ministry of National Guard Health Affairs. Definitions and methodology of HAIs and antimicrobial resistance were based on NHSN. Consecutive NHSN reports were used for comparisons. Results A total 1544 pathogens causing 1531 HAI events were included. Gram negative pathogens (GNP) were responsible for 63% of HAIs, with a significant increasing trend in Klebsiella spp. and a decreasing trend in Acinetobacter . Methicillin-resistant Staphylococcus aureus (27.0%) was consistently less frequent than NHSN. Vancomycin-resistant Enterococci (VRE, 20.3%) were more than doubled during the study, closing the gap with NHSN. Carbapenem resistance was highest with Acinetobacter (68.3%) and Pseudomonas (36.8%). Increasing trends of carbapenem resistance were highest in Pseudomonas and Enterobacteriaceae , closing initial gaps with NHSN. With the exception of Klebsiella and Enterobacter , multidrug-resistant (MDR) GNPs were generally decreasing, mainly due to the decreasing resistance towards cephalosporins, fluoroquinolones, and aminoglycosides. Conclusion The findings showed increasing trends of carbapenem resistance and VRE, which may reflect heavy use of carbapenems and vancomycin. These findings may highlight the need for effective antimicrobial stewardship programs, including monitoring and feedback on antimicrobial use and resistance.