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Carbapenem-resistant Klebsiella pneumoniae (CRKP) represents a critical global health threat, with ST101 identified as a major circulating clone in Saudi Arabia. We used whole genome sequencing and plasmid reconstruction to investigate the molecular characteristics of CRKP ST101 isolates from Saudi Arabia (2018–2021), analyzing antimicrobial resistance genes (ARGs), virulence factors, and plasmid structure and replicon types. Clinical isolates were obtained from the Ministry of National Guard Health Affairs (MNGHA) hospitals in Saudi Arabia between 2018 and 2021. Whole-genome sequencing was performed using the Illumina MiSeq® platform, followed by comprehensive bioinformatic analysis of ARGs, virulence factors, and plasmid content. All ten isolates belonged to ST101 and harbored extensive antimicrobial resistance (AMR) and virulence determinants. Nine isolates (90%) carried blaOXA-48, with three co-harboring blaNDM-1, representing dual-carbapenemase producers. These carbapenemase genes were located on plasmids with distinct replicon types, including IncL/M, IncHI1B/IncFIB, and IncFIA/IncR. All isolates were multidrug-resistant (MDR), with half classified as extensively drug-resistant (XDR). Four isolates exhibited hypervirulent profiles, harboring aerobactin and yersiniabactin siderophores. This study provides comprehensive genomic characterization of CRKP ST101 in Saudi Arabia, revealing complex resistance mechanisms mediated by diverse plasmid types. The findings highlight the importance of genomic surveillance to track the evolution and dissemination of high-risk MDR and XDR lineages and inform targeted infection control strategies.

Bloodstream infection among hospitalized patients is associated with serious adverse outcomes. Blood culture is routinely ordered in patients with suspected infections, although 90% of blood cultures do not show any growth of organisms. The evidence regarding the prediction of bacteremia is scarce. A retrospective review of blood cultures requested for a cohort of admitted patients between 2017 and 2019 was undertaken. Several machine-learning models were used to identify the best prediction model. Additionally, univariate and multivariable logistic regression was used to determine the predictive factors for bacteremia. A total of 36,405 blood cultures of 7157 patients were done. There were 2413 (6.62%) positive blood cultures. The best prediction was by using NN with the high specificity of 88% but low sensitivity. There was a statistical difference in the following factors: longer admission days before the blood culture, presence of a central line, and higher lactic acid-more than 2 mmol/L. Despite the low positive rate of blood culture, machine learning could predict positive blood culture with high specificity but minimum sensitivity. Yet, the SIRS score, qSOFA score, and other known factors were not good prognostic factors. Further improvement and training would possibly enhance machine-learning performance.

Despite low infectious potential of extrapulmonary tuberculosis (EPTB), it poses significant clinical challenges in terms of diagnosis and treatment monitoring. Understanding the main demographical risk factors for disease characteristics of EPTB plays a crucial role in speeding up diagnosis process and improving overall clinical experience. The aim of this study was to investigate the main demographical and clinical risk factors for EPTB among adults and adolescents for the first time in Saudi Arabia. A cross-sectional multicenter study was carried out on a collection of 902 extrapulmonary Mycobacterium tuberculosis complex (MTBC) isolates with demographical and clinical data. All isolates were subjected to spoligotyping and 24-loci based MIRU-VNTR typing. The association between two potential variables was assessed using odd ratios (OR) calculations. Independent risk factors for EPTB and diseases characteristics of EPTB were identified using multivariate regression model analyses. Gender was found to be significantly associated with lymph node, gastrointestinal, central nervous system and urogenital TB. Lymph node TB showed statistical association to age group below 25 years, non-Saudis and South East Asian ethnicity. While gastrointestinal TB demonstrated an association with patients above 60 years old, and Saudis. Multivariate analysis showed that gender is an independent risk factor to urogenital TB (p 0.03) and lymph node TB (p 0.005). On the other hands, South Asian (p 0.01) and South East Asian (p 0.03) ethnicities were both identified as independent risk factors significantly associated with EPTB. MTBC lineages, site of infections, gender, HIV and smear positivity showed no significant association. Nationwide qualitative-studies are highly warranted in the future to further understand the main demographic risk factors for disease characteristics of EPTB.

The Middle East respiratory syndrome (MERS) is a coronavirus (CoV)-mediated respiratory disease. Virus transmission occurs within health care settings, but cases also appear sporadically in the community. Camels are believed to be the source for community-acquired cases, but most patients do not have camel exposure. Here, we assessed whether camel workers (CWs) with high rates of exposure to camel nasal and oral secretions had evidence of MERS-CoV infection. The results indicate that a high percentage of CWs were positive for virus-specific immune responses but had no history of significant respiratory disease. Thus, a possible explanation for repeated MERS outbreaks is that CWs develop mild or subclinical disease. These CWs then transmit the virus to uninfected individuals, some of whom are highly susceptible, develop severe disease, and are detected as primary MERS cases in the community. Middle East respiratory syndrome (MERS), a highly lethal respiratory disease caused by a novel coronavirus (MERS-CoV), is an emerging disease with high potential for epidemic spread. It has been listed by the WHO and the Coalition for Epidemic Preparedness Innovations (CEPI) as an important target for vaccine development. While initially the majority of MERS cases were hospital acquired, continued emergence of MERS is attributed to community acquisition, with camels likely being the direct or indirect source. However, the majority of patients do not describe camel exposure, making the route of transmission unclear. Here, using sensitive immunological assays and a cohort of camel workers (CWs) with well-documented camel exposure, we show that approximately 50% of camel workers (CWs) in the Kingdom of Saudi Arabia (KSA) and 0% of controls were previously infected. We obtained blood samples from 30 camel herders, truck drivers, and handlers with well-documented camel exposure and from healthy donors, and measured MERS-CoV-specific enzyme-linked immunosorbent assay (ELISA), immunofluorescence assay (IFA), and neutralizing antibody titers, as well as T cell responses. Totals of 16/30 CWs and 0/30 healthy control donors were seropositive by MERS-CoV-specific ELISA and/or neutralizing antibody titer, and an additional four CWs were seronegative but contained virus-specific T cells in their blood. Although virus transmission from CWs has not been formally demonstrated, a possible explanation for repeated MERS outbreaks is that CWs develop mild disease and then transmit the virus to uninfected individuals. Infection of some of these individuals, such as those with comorbidities, results in severe disease and in the episodic appearance of patients with MERS. IMPORTANCE The Middle East respiratory syndrome (MERS) is a coronavirus (CoV)-mediated respiratory disease. Virus transmission occurs within health care settings, but cases also appear sporadically in the community. Camels are believed to be the source for community-acquired cases, but most patients do not have camel exposure. Here, we assessed whether camel workers (CWs) with high rates of exposure to camel nasal and oral secretions had evidence of MERS-CoV infection. The results indicate that a high percentage of CWs were positive for virus-specific immune responses but had no history of significant respiratory disease. Thus, a possible explanation for repeated MERS outbreaks is that CWs develop mild or subclinical disease. These CWs then transmit the virus to uninfected individuals, some of whom are highly susceptible, develop severe disease, and are detected as primary MERS cases in the community.

Background/Objectives: Central nervous system (CNS) infections remain a significant public health challenge and require rapid and accurate diagnosis to guide clinical management. Although the incidence of bacterial meningitis has declined owing to widespread vaccination, viral etiologies continue to dominate CNS infections. The aim of this study was to assess the epidemiological trends, age distribution, and seasonality of CNS infections using multiplex PCR. Methods: A retrospective analysis was conducted on cerebrospinal fluid (CSF) samples collected between January 2021 and December 2022 from patients with CNS infections at King Abdulaziz Medical City. A BioFire FilmArray Meningitis/Encephalitis (ME) panel was used to detect pathogens. Patient demographics, pathogen distribution, and seasonal trends were analyzed. Results: A total of 2460 CSF samples were tested, of which 130 (5%) were positive for at least one pathogen. Viral pathogens accounted for 82.3% of the infections, with human herpesvirus-6 (HHV-6) (31%) and enterovirus (EV) (20%) being the most common. Bacterial pathogens represented 17.7% of the cases, with Streptococcus pneumoniae (6%) and Escherichia coli K1 (5%) being the predominant bacterial agents. The highest infection burden was observed in infants aged 0–6 months, with a marked male predominance. Seasonal analysis revealed multiple peaks in viral infections, particularly of HHV-6 and EVs, whereas bacterial infections were sporadic, with Streptococcus agalactiae and Streptococcus pneumoniae peaking in October and November. Conclusions: Viral infections, particularly HHV-6 and EVs, dominated CNS infections, with distinct seasonal and age-related variations. These findings underscore the value of multiplex PCR in improving the rapid diagnosis of CNS infections and aiding in timely treatment and antimicrobial stewardship.

Patients in the ICU have encountered an increasing emergence and spread of antibiotic-resistant pathogens. We examined patterns of antimicrobial susceptibility in gram-negative isolates to commonly used drugs in an adult ICU at a tertiary care hospital in Riyadh, Saudi Arabia. A retrospective study was carried out of gram-negative isolates from the adult ICU of King Fahad National Guard Hospital (KFNGH) between 2004 and 2009. Organisms were identified and tested by an automated identification and susceptibility system, and the antibiotic susceptibility testing was confirmed by the disk diffusion method. The most frequently isolated organism was Acinetobacter baumannii, followed by Pseudomonas aeruginosa, Escherichia coli, Klebsiella pnemoniae, Stenotrophomonas maltophilia, and Enterobacter. Antibiotic susceptibility patterns significantly declined in many organisms, especially A baumannii, E coli, S marcescens, and Enterobacter. A baumannii susceptibility was significantly decreased to imipenem (55% to 10%), meropenem (33% to 10%), ciprofloxacin (22% to 10%), and amikacin (12% to 6%). E coli susceptibility was markedly decreased (from 75% to 50% or less) to cefuroxime, ceftazidime, cefotaxime, and cefepime. S marcescens susceptibility was markedly decreased to cefotaxime (100% to 32%), ceftazidime (100% to 35%), and cefepime (100% to 66%). Enterobacter susceptibility was markedly decreased to ceftazidime (34% to 5%), cefotaxime (34% to 6%), and pipracillin-tazobactam (51% to 35%). Respiratory samples were the most frequently indicative of multidrug-resistant pathogens (63%), followed by urinary samples (57%). Antimicrobial resistance is an emerging problem in the KFNGH ICU, justifying new more stringent antibiotic prescription guidelines. Continuous monitoring of antimicrobial susceptibility and strict adherence to infection prevention guidelines are essential to eliminate major outbreaks in the future.

The objective of this study is to examine the IgG antibody response in critically ill patients with the Middle East respiratory syndrome (MERS) and to examine the association of early antibody response with mortality and viral clearance. We collected blood samples from 40 consecutive real-time reverse transcription-polymerase chain reaction (rRT-PCR) confirmed critically ill MERS patients on ICU days 1, 3, 7, 14 and 28. MERS-CoV antibodies were detected by enzyme-linked immunosorbent assay (ELISA), using wells coated with MERS-CoV S1 antigen. Patients were admitted to ICU after a median (Q1, Q3) of 9 (4, 13) days from onset of symptoms with an admission Sequential Organ Failure Assessment (SOFA) score of 11 (6.5, 12). Among the study cohort, 38 patients (95%) received invasive ventilation, 35 (88%) vasopressors, 21 (53%) renal replacement therapy and 17 (43%) corticosteroids. Median (Q1,Q3) ELISA optical density (OD) ratio significantly increased with time (p < 0.001) from 0.11 (0.07, 1.43) on day 1; to 0.69 (0.11, 2.08) on day 3, 2.72 (1.84, 3.54) on day 7, 2.51 (0.35, 3.35) on day 14 and 3.77 (3.70, 3.84) on day 28. Early antibody response (day 1–3) was observed in 13/39 patients (33%) and was associated with lower mortality (hazard ratio: 0.31, 95% CI 0.10, 0.96, p = 0.04) but was not associated with faster clearance of MERS-CoV RNA. In conclusion, among critically ill patients with MERS, early antibody response was associated with lower mortality but not with faster clearance of MERS-CoV RNA. These findings have important implications for understanding pathogenesis and potential immunotherapy.

Background Antibiotics significantly increased life expectancy and decreased mortality rates due to infections. However, this trend is starting to fade with the rise of multidrug-resistant organisms (MDR); these strains are becoming a global burden on healthcare and the economy. The dramatic increase and spread of carbapenem-resistant gram-negative bacteria (CRGNB) has become a serious global public health concern. In this retrospective cross-sectional study, we aimed to estimate the rates of gram-negative bacteremia in five tertiary care hospitals in different geographical locations in Saudi Arabia for five years. Methods A retrospective cross-sectional study was conducted in five tertiary care hospitals in Saudi Arabia among patients with bacteremia due to CRGNB. Electronic medical records were used to retrieve data regarding patient demographics and antimicrobial susceptibility testing (AST) over five years between January 2016 and December 2020. Patients with positive blood cultures for carbapenem-resistant and comprise the final study population. Results This retrospective multicentric study was conducted between 2016 and 2020 in five tertiary care hospitals across five cities in Saudi Arabia. (n=2190, 38.03%), (n=2154, 37.41%), (n = 918, 15.94%), and (n=496, 8.61%) constitute the 5758 gram-negative bacteria isolates. was the most frequently identified species in Riyadh, AlAhsa, Dammam, and Madinah (40%, 46.50%, 61.67%, and 43.66%, respectively), with a p-value of (p<0.001), except in Jeddah, where was the most prevalent (42%). The mean age of patients across Riyadh, AlAhsa, Dammam, and Madinah was 62.2 years (± 4.24). In contrast to Jeddah, where the majority of isolates (702; 41.8%) belonged to the adult age group. Most isolates were from male patients (3045; 52.9%), compared to 2713 (47.1%) from female patients. 1226 (40.3%) was the most prevalent isolate among male patients while  (1135; 41.8%) was the most prevalent isolate among female patients. Conclusion Our study showed that the prevalence of carbapenem non-susceptible Gram-negative bacteria is relatively high, which therefore makes them very challenging to treat. The results show an urgent need for improved antibiotic stewardship strategies, including better surveillance and more effective infection control measures to reduce this issue. Further research into the molecular epidemiology and risk factors associated with these infections is necessary to guide public health policymakers in developing interventions to help control the spread of carbapenem-resistant Gram-negative bacteria.

Empirical antimicrobial therapy (EAT) for Acinetobacter infections may not be appropriate as it tends to be multidrug-resistant. This study evaluated the relationship between appropriate EAT and the outcomes of Intensive Care Unit (ICU) patients with Acinetobacter bacteremia. This is a retrospective study of patients admitted to a medical-surgical ICU (2005-2010) and developed Acinetobacter bacteremia during the stay. Patients were categorized according to EAT appropriateness, defined as administration of at least one antimicrobial agent to which the Acinetobacter was susceptible before susceptibility results were known. The relation between EAT appropriateness and outcomes was evaluated. Sixty patients developed Acinetobacter bacteremia in the 6-year period (age = 50 ± 19 years; 62% males; Acute Physiology and Chronic Health Evaluation II score = 28 ± 9; 98.3% with central lines; 67% in shock and 59% mechanically ventilated) on average on day 23 of ICU and day 38 of hospital stay. All isolates were resistant to at least three of the tested antimicrobials. Appropriate EAT was administered to 60% of patients, mostly as intravenous colistin. Appropriate EAT was associated with lower ICU mortality risk (odds ratio: 0.15; 95% confidence interval: 0.03-0.96) on multivariate analysis. In this 6-year cohort, Acinetobacter bacteremia was related to multidrug-resistant strains. Appropriate EAT was associated with decreased ICU mortality risk.

To describe local experience in managing an outbreak of Candida auris in a tertiary-care setting. In response to emerging Candida auris, an outbreak investigation was conducted at our hospital between March 2018 and June 2019. Once a patient was confirmed to have Candida auris, screening of exposed patients and healthcare workers (HCWs) was conducted. Postexposure screening included those who had had direct contact with or shared the same unit or ward with a laboratory-confirmed case. In response to the increasing number of cases, new infection control measures were implemented. In total, 23 primary patients were detected over 15 months. Postexposure screening identified 11 more cases, and all were patients. Furthermore, ~28.6% of patients probably caught infection in another hospital or in the community. Infection control measures were strictly implemented including hand hygiene, personal protective equipment, patient hygiene, environmental cleaning, cohorting of patients and HCWs, and avoiding the sharing of equipment. The wave reached a peak in April 2019, followed by a sharp decrease in May 2019 and complete clearance in June 2019. The case patients were equally distributed between intensive care units (51.4%) and wards (48.6%). More infections (62.9%) occurred than colonizations (37.1%). Urinary tract infection (42.9%) and candidemia (17.1%) were the main infections. In total, 7 patients (20.0%) died during hospitalization; among them, 6 (17.1%) died within 30 days of diagnosis. Active screening of exposed patients followed by strict infection control measures, including environmental cleaning, was successful in ending the outbreak. Preventing future outbreaks is challenging due to outside sources of infection and environmental resistance.