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Abstract 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

Background: Candida auris, an emerging multidrug-resistant fungus species that grows as yeast, causes bloodstream infection, and is associated with high mortality rates. In this study, we identified risk factors associated with C. auris bloodstream infection, antifungal susceptibility pattern, complications, and outcome of the infection. Methods: This single-center cross-sectional retrospective study was conducted at King Abdulaziz Medical City, a tertiary care facility in Jeddah, Saudi Arabia, which included all patients 18 years or above who have had one or more blood cultures for C. auris between January 2021 and December 2022. We aimed to identify the risk factors associated with C. auris bloodstream infection, antifungal susceptibility patterns, complications, and outcomes at our center. Results: Forty-six patients with C. auris-positive blood cultures were included. All the patients had healthcare-associated infections. The mean age was 64.67 years, and the majority of patients were male (73.9 %). The most common concomitant hospital-acquired infections were skin and soft tissue infections (37 %), followed by hospital-acquired pneumonia (34.8 %) and intra-abdominal infections (26.1 %). The mean total white blood cell count, procalcitonin, and C-reactive protein was 10.5 ± 5.99 × 109/L, 2.63 ± 4.82 μg/L, and 90.3 ± 64.1 mg/L, respectively. Hypertension (73.9 %) was the most common comorbidity, followed by diabetes mellitus (58.7 %) and renal dysfunction (54.3 %). Risk factors associated with C. auris candidemia included antibiotic use (91.3 %), especially for > 14 days (78.3 %), C. auris colonization (60.9 %), use of central venous catheters, especially when the catheter was in place for >30 days (80.4 %), ICU admission in the last 30 days before C. auris-positive blood culture (93.5 %), especially for more than two weeks (76.1 %), mechanical ventilation (89.1 %), total parenteral nutrition (13 %), previous intra-abdominal surgery (30.4 %), and immunosuppressive therapy (56.5 %). A total of 97.8 % of C. auris isolates were resistant to fluconazole and 17.4 % were resistant to amphotericin B. Endocarditis and endophthalmitis were reported in one (2.2 %) patient each. The all-cause mortality at 30 days was 47.8 %. Conclusion: Our study is one of the few studies available globally on C. auris bloodstream infection that investigated risk factors, antifungal susceptibility, complications, and outcomes. A thorough screening and risk assessment strategy should aid infection control, preventing it from becoming a major concern in the future.

Background: Nosocomial outbreaks frequently occurred during the Coronavirus disease 2019 (COVID-19) pandemic; however, sharing experiences on outbreak containment is vital to reduce the related burden in different locations. Objectives: This article aims at sharing a practical experience on COVID-19 outbreak containment, including contact tracing, screening of target population, testing including molecular analysis, and preventive modalities. It also provides an epidemiological and molecular analysis of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS‑CoV‑2) infection outbreak in a tertiary care hospital in Saudi Arabia. Methods: The outbreak occurred in a non-COVID medical ward at a tertiary care hospital in Jeddah, Saudi Arabia, from 22nd March and 15th April 2021. The multidisciplinary outbreak response team performed clinical and epidemiological investigations. Whole-Genome Sequencing (WGS) was implemented on selected isolates for further molecular characterization. Results: A total of eight nurses (20 % of the assigned ward nurses) and six patients (16.2 % of the ward admitted patients at the time of the outbreak) tested positive for the SARS-CoV-2 virus based on PCR testing. The outbreak investigation identified strong evidence of an epidemiologic link between the affected cases. WGS revealed a set of spike mutations and deletions specific to the Alpha variant (B.1.1.7 lineage). All the nurses had mild symptoms, and the fatality among the patients was 50 % (three out of the six patients). Conclusions: The current nosocomial COVID-19 outbreak, caused by the Alpha variant, revealed multiple breaches in the adherence to the hospital infection control recommended measures. Containment strategies were successful in controlling the outbreak and limiting infection spread. Molecular analysis and genome sequencing are essential tools besides epidemiological investigation to inform appropriate actions, especially with emerging pathogens.

Background: Clostridium difficile is an anaerobic gram-positive spore-forming bacillus that is most commonly associated with nosocomial diarrhea. This study aimed to analyze the prevalence and risk factors of Clostridium difficile infection (CDI) at a tertiary health care center, Western region, Saudi Arabia. We also aimed to examine the duration of exposure to each risk factor prior CDI development, and to categorize CDI as severe and non-severe depending on the white blood cell (WBC) count. Various complications of the infection were also analyzed. Methods: We performed a retrospective chart review of all patients who had a positive nucleic acid amplification test (NAAT) for Clostridium difficile toxin genes between October 2018 and October 2020. Results: The prevalence of CDI among the included patients was 9.1% (237 of 2611 patients). The mean age (standard deviation) was 56.86 (21) years, and the infection was more prevalent among men (52.74%) than among women (47.26%). The most common risk factor associated with CDI was recent antibiotic use (74.68%), followed by recent acid suppressant use (67.50%), malignancy (46%), and previous gastrointestinal surgery (6.30%). The CDI recurrence rate was 13.90%. Piperacillin-tazobactam was the most frequently used broad-spectrum antibiotic, and was used in 38.8% of the patients, followed by meropenem. The most common malignancy type was lymphoma (22.94%, n = 25), followed by leukemia (n = 23). The most common type of surgery was subtotal colectomy (n = 6). Three patients underwent transverse colon resection, and two underwent ileocecal resection. Hypotension was the most frequently recorded complication (28.40%) in the study population. Conclusion: The prevalence rate of CDI among the study patients during the two-year study from October 2018 to October 2020 was 9.1%. Appropriate use of antibiotic and acid suppressants, and contact isolation measures can help in decreasing the number of CDI cases.

We report two cases of inflammatory reaction to postvaccination to Pfizer COVID-19 vaccine from Saudi Arabia: A case of delayed inflammatory reactions (DIRs) to hyaluronic acid (HA) dermal filler in the upper lip following the first dose of messenger ribonucleic acid Pfizer-BioNTech COVID-19 vaccine; the second case of DIR to HA filler underneath of eye following the second dose of Pfizer COVID-19 vaccine. The mechanism of this late reaction to HA fillers may be dependent on numerous factors and is not well understood.

Healthcare workers have been categorized among the priority groups for COVID-19 vaccination. However, post-vaccination infections have been identified. This study was conducted to investigate SARS-CoV-2 infection among healthcare workers (HCWs) who received the COVID-19 vaccine. A case series in a multicenter healthcare system in Saudi Arabia was created from HCWs who had (PCR-RT) confirmed SARS-CoV-2 infection after at least one dose of Pfizer-BioNTech vaccination. A total of 20 healthcare workers (HCWs) have been included. The majority (70.0%) were males and the average age was 39.4 ± 10.1 years. They included physicians (55.0%), nurses (25.0%) and other HCWs (20.0%). Eighteen (90%) HCWs had infection after the first dose; 47.1% within the first week, 41.2% within the second week, and 11.8% within the third week. Only two HCWs (10.0%) had infection one week after the second dose. The majority (63.2%) had mild (52.6%) or moderate (10.3%) disease with no severe disease or hospitalization. The majority of post-vaccination COVID-19 infections among HCWs occurred before the full protection of the vaccine is gained. Suspicion of COVID-19 infection should be considered even with a history of COVID-19 vaccination. Recently vaccinated HCWs should be advised to fully comply with all recommended precautions to prevent COVID-19 transmission.

Deep learning has massive potential in predicting phenotype from different omics profiles. However, deep neural networks are viewed as black boxes, providing predictions without explanation. Therefore, the requirements for these models to become interpretable are increasing, especially in the medical field. Here we propose a computational framework that takes the gene expression profile of any primary cancer sample and predicts whether patients’ samples are primary (localized) or metastasized to the brain, bone, lung, or liver based on deep learning architecture. Specifically, we first constructed an AutoEncoder framework to learn the non-linear relationship between genes, and then DeepLIFT was applied to calculate genes’ importance scores. Next, to mine the top essential genes that can distinguish the primary and metastasized tumors, we iteratively added ten top-ranked genes based upon their importance score to train a DNN model. Then we trained a final multi-class DNN that uses the output from the previous part as an input and predicts whether samples are primary or metastasized to the brain, bone, lung, or liver. The prediction performances ranged from AUC of 0.93–0.82. We further designed the model’s workflow to provide a second functionality beyond metastasis site prediction, i.e., to identify the biological functions that the DL model uses to perform the prediction. To our knowledge, this is the first multi-class DNN model developed for the generic prediction of metastasis to various sites.

Knowing metastasis is the primary cause of cancer-related deaths, incentivized research directed towards unraveling the complex cellular processes that drive the metastasis. Advancement in technology and specifically the advent of high-throughput sequencing provides knowledge of such processes. This knowledge led to the development of therapeutic and clinical applications, and is now being used to predict the onset of metastasis to improve diagnostics and disease therapies. In this regard, predicting metastasis onset has also been explored using artificial intelligence approaches that are machine learning, and more recently, deep learning-based. This review summarizes the different machine learning and deep learning-based metastasis prediction methods developed to date. We also detail the different types of molecular data used to build the models and the critical signatures derived from the different methods. We further highlight the challenges associated with using machine learning and deep learning methods, and provide suggestions to improve the predictive performance of such methods.

Objectives: There is local and regional deficiency in the data examining the contribution of resistant pathogens to device-associated healthcare-associated infections (DA-HAIs). The objective was to examine such data in a multi-hospital system in Saudi Arabia in comparison with the US National Health Surveillance Network (NHSN). Methods: Surveillance of DA-HAIs was prospectively conducted between 2008 and 2016 in four hospitals of Ministry of National Guard Health Affairs. Consecutive NHSN reports were used for comparisons. Definitions and methodology of DA-HAIs and bacterial resistance were based on NHSN. Results: A total 1260 pathogens causing 1141 DA-HAI events were included. Gram negative pathogens (GNPs) were responsible for 62.5% of DA-HAIs, with a significantly higher Klebsiella, Pseudomonas, Acinetobacter, and Enterobacter than NHSN hospitals. Approximately 28.3% of GNPs and 23.5% of gram positive pathogens (GPPs) had some type of resistance. Nearly 34.3% of Klebsiella were resistant to third/fourth generation cephalosporins, 4.8% of Enterobacteriaceae were carbapenem-resistant (CRE), 24.4% of Staphylococcus aureus were methicillin-resistant (MRSA), and 21.9% of Enterococci were vancomycin-resistant (VRE). Multidrug resistance (MDR) was 65.0% in Acinetobacter, 26.4% in Escherichia coli, 23.0% in Klebsiella, and 14.9% in Pseudomonas. Resistant GNPs including cephalosporin-resistant Klebsiella, MDR Klebsiella, and MDR Escherichia coli were significantly more frequent while resistant GPPs including MRSA and VRE were significantly less frequent than NHSN hospitals. Conclusion: The current findings showed heavier and more resistant contribution of GNPs to DA-HAIs in Saudi hospitals compared with American hospitals. The higher resistance rates in Klebsiella and Escherichia coli are alarming and call for effective antimicrobial stewardship programs.

Abstract 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.

Brevibacterium species are to be opportunistic pathogens. Although rare, several case reports have mentioned infections ranging from cutaneous infections to bacteremia. Here, we present a case report describing a 64-year-old male pancreatic cancer patient diagnosed with B. luteolum bacteremia.

Abstract 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.

We describe the clinical and genetic characteristics of multi-drug resistant tuberculosis (MDR-TB) in a family cluster in the western region of Kingdom of Saudi Arabia diagnosed between 2012 and 2016. All cases had risk factors for tuberculosis acquisition and they were not household contacts of the index case. Genetic analysis detected both MDR-TB and pre-extensively drug-resistant tuberculosis (pre-XDR TB) strains in the index case and confirmed tuberculosis transmission between two cases. Lack of early diagnosis of MDR-TB by molecular testing and lack of extended contact tracing contributed to the transmission of MDR-TB among this family cluster over four years. Keywords: Multidrug resistant tuberculosis, Family cluster

Abstract 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.

Abstract Background Nosocomial infections caused by multi-drug resistant Enterobacteriaceae are a global public health threat that ought to be promptly identified, reported, and addressed accurately. Many carbapenem-resistant Enterobacteriaceae-associated genes have been identified in Saudi Arabia but not the endemic Klebsiella pneumoniae carbapenemases (KPCs), which are encoded by bla KPC-type genes. KPCs are known for their exceptional spreading potential. Methods We collected n = 286 multi-drug resistant (MDR) Klebsiella spp. 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. Results A Carbapenem-resistant Enterobacteriaceae (CRE) Klebsiella quasipneumoniae subsp. similipneumoniae strain was identified as a novel ST-3510 carrying a bla KPC-2 carbapenemase encoding gene. The isolate, designated as NGKPC-421, was obtained from shotgun Whole Genome Sequencing (WGS) surveillance of 286 MDR Klebsiella spp. clinical isolates. The NGKPC-421 isolate was collected from a septic patient in late 2017 and was initially misidentified as K. pneumoniae. The sequencing and assembly of the NGKPC-421 genome resulted in the identification of a putative ~ 39.4 kb IncX6 plasmid harboring a bla KPC-2 gene, flanked by transposable elements (ISKpn6-bla KPC-2–ISKpn27). Conclusion 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.

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.

Objectives The present study was conducted to estimate the seroprevalence of antibody to pertussis toxin among adult populations in western Saudi Arabia.Design A cross-sectional study.Setting King Abdulaziz Medical City, Jeddah, western Saudi Arabia. A tertiary care teaching hospital.Participants A 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.Interventions The study included the analysis of serum blood samples using commercial ELISA. A consecutive sampling technique was applied.Primary outcome measures Seropositivity of antipertussis toxin immunoglobulin G (anti-PT IgG) ≥62.5 IU/mL.Results Antibody 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 (

Abstract 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.