The emergence of highly resistant and hypervirulent Klebsiella pneumoniae CC14 clone in a tertiary hospital over 8 years.

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 ß-lactamase (ESBL) and carbapenemase genes, namely blaOXA-48 and blaOXA-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.

COVID-19 Vaccination Knowledge and Attitude Among the General Population in Jeddah, Saudi Arabia.

Background The population's hesitancy to get the coronavirus disease 2019 (COVID-19) vaccination may pose a risk to public health worldwide. However, the causes and contributors to vaccine hesitancy in the Saudi people need to be understood. This study aimed to assess the knowledge and attitudes toward COVID-19 vaccination among the general population in Jeddah, Saudi Arabia. Methodology A cross-sectional study was conducted using an online structured questionnaire titled "Knowledge and attitude toward COVID-19 vaccination." The questionnaire collected demographic characteristics, knowledge, and attitudes toward COVID-19 vaccination among the general population in Jeddah, Saudi Arabia. The questionnaire was distributed through links on various sites, including Twitter and WhatsApp. Results A total of 544 participants were included in the present study. Overall, 64.9% were males, and 35.1% were females. Most of the population had received three doses (83.6%) of the COVID-19 vaccine. About half of the participants had a university education (56.8%), 17.5% of respondents were postgraduates, and 14.2% had secondary education. Overall, 41.4% of the population had a low knowledge level, and 58.5% had a low attitude toward COVID-19 vaccination. Receiving the COVID-19 vaccine was significantly (p < 0.05) associated with the population's knowledge and attitude toward COVID-19 vaccination. In addition, the education level substantially affected the knowledge and attitude toward COVID-19 vaccination. Additionally, knowledge of COVID-19 vaccination had a significant correlation (p < 0.05) with the attitude toward the vaccine. Conclusions Despite the high prevalence of the population who received the three doses of the COVID-19 vaccine in Jeddah city, the study showed insufficient knowledge and attitude among the population toward COVID-19 vaccination. However, fortunately, education plays an essential role in improving the knowledge of COVID-19 vaccination.

COVID-19 Vaccine Knowledge and Attitude Among Healthcare Workers in Jeddah, Saudi Arabia.

Background On March 11, 2020, the World Health Organization (WHO) proclaimed coronavirus disease 2019 (COVID-19) a pandemic. COVID-19 can result in asymptomatic infection, severe pneumonia, and death. In this study, healthcare workers in Jeddah, Saudi Arabia, were asked to reflect on their knowledge of and attitudes toward the COVID-19 vaccine. Methods Online anonymous polling of healthcare professionals in Jeddah, Saudi Arabia, was done. During the COVID-19 pandemic, the respondents' demographic information and knowledge of and attitudes toward the COVID-19 vaccine were gathered through a questionnaire. Both descriptive and inferential statistics were used to analyze the data. Results The knowledge of the responders for each vaccine is as follows: Pfizer-BioNTech, 96.1%; AstraZeneca-Oxford, 66.1%; Moderna, 56.9%; and Johnson & Johnson's Janssen, 18.2%. A small percentage of responders (5.7%) believe that COVID-19 vaccination may alter their DNA, while 70% believe it can prevent them from getting sick with COVID-19 infection. Half of the responders had a wrong opinion of COVID-19 vaccinations. Conclusion The findings imply that improving healthcare workers' knowledge of vaccines and changing attitudes toward vaccination may increase vaccine acceptability. This would involve addressing the respondents' concerns about vaccine side effects and their general mistrust of vaccine benefits.

Evidence-Based Interventions to Reduce the Incidence of Common Multidrug-Resistant Gram-Negative Bacteria in an Adult Intensive Care Unit.

Background Multidrug-resistant Gram-negative bacteria (MDR-GNB) present a significant and escalating hazard to healthcare globally. Context-specific interventions have been implemented for the prevention and control of MDR-GNB in several healthcare facilities. The objective of this study was to implement and evaluate the effectiveness of evidence-based interventions in the incidence and dissemination of MDR-GNB. Methods This was a pre-and post-intervention study conducted in three phases at King Abdulaziz Medical City Jeddah, Saudi Arabia. During Phase-1, the data on each of the four MDR-GNB (Acinetobacter baumannii, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Escherichia coli) were collected prospectively. Genomic fingerprinting was performed on isolates using enterobacterial repetitive intergenic consensus-polymerase chain reaction (ERIC-PCR) to determine clonality and establish a link between different strains within and between the hospital wards/units. In the second phase, targeted interventions were implemented in the adult intensive care unit (ICU) based on previously determined risk factors and included the education of healthcare workers on hand hygiene, disinfection of patients' surrounding, daily chlorhexidine baths, and disinfection rooms on discharge with hydrogen peroxide fogging after MDR-GNB patients were discharged. An antibiotic restriction protocol was simultaneously implemented as part of the hospital antibiotic stewardship program. In the third phase, the effectiveness of the interventions was evaluated by comparing the incidence rate and clonality (using ERIC-PCR genetic fingerprints) of MDR-GNB before and after the intervention. Results A significant reduction of MDR-GNB was observed in Phase-2 and Phase-3 compared with Phase-1. The mean incidence rate of MDR-GNB per 1000 patient days in Phase-1 (pre-intervention) was 11.08/1000, followed by 6.07 and 3.54/1000 in Phase-2 and Phase-3, respectively. A statistically significant reduction was observed in the incidence rate of MDR-GNB in the adult ICU (P=0.007), whereas no statistically significant decrease (P=0.419) was observed in areas other than the adult ICU. Two A. baumannii strains appear to be circulating within the ICU environment with reduced frequency in Phase-2 and Phase-3 compared to Phase-1. Conclusion  There was a significant reduction in the incidence of MDR-GNB in the adult ICU due to the successful implementation of both infection control and stewardship interventions, albeit challenging to ascertain the relative contribution of each.

Risk Factors for Infection With Multidrug-Resistant Gram-Negative Bacteria in a Tertiary Care Hospital in Saudi Arabia: A Case-Control Study.

Background The increase in the incidence of multidrug-resistant (MDR) organisms especially Gram-negative bacteria (GNB) in healthcare facilities is a serious cause of concern. This study identified risk factors for the infection with these MDR GNB, such as Acinetobacter baumannii, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Escherichia coli to inform healthcare workers about strategies for their containment. Methods A case-control study was carried out at a tertiary care hospital where 100 patients with healthcare-associated infections (infections arising 48 hours after admission) caused by MDR GNB were compared with two control groups, i.e., 100 patients with healthcare-associated infections caused by non-MDR GNB (not meeting the criteria of MDR) and 100 patients without infection caused by GNB. MDR bacteria were defined as the ones that were non-susceptible to at least one antibiotic in three or more classes of antibiotics. The data were analyzed using descriptive statistics (frequency and percentage of categorical variables). Multivariate regression analysis was undertaken to identify significant predictors of MDR GNB. Odds ratios with 95% confidence intervals were calculated, and the level of significance was determined at p-value < 0.05. Results A total of 388 organisms were isolated during four months (January-April 2015) from 332 patients. Fifty-six (17%) of the patients were infected with more than one organism. Among the MDR bacteria, the most dominant MDR organism was A. baumannii (38%), followed by K. pneumoniae (31%), P. aeruginosa (20%), and E. coli (11%). Among the non-MDR organisms, the most dominant was P. aeruginosa (47%), followed by E. coli (32%), K. pneumoniae (18%), and A. baumannii (3%). Patients with MDR organisms compared with the first control group (patients with non-MDR organisms) showed that prior antibiotic use (p-value: 0.001), intensive care unit (ICU) admission (p-value: 0.001), and indwelling medical devices (p-value: 0.005) were significant risk factors for MDR infections. It was also found that the risk factors for MDR GNB infection were the same in the second control group (patients without infection): prior antibiotic use (p-value: 0.002), ICU admission (p-value: 0.001), and indwelling medical devices (p-value: 0.03). Based on the comparison of the two control groups, prolonged hospital stays of more than five days (p-value: 0.001), immunosuppressive therapy (p-value: 0.02), and over 60 years of age (p-value: 0.02) were significant risk factors for non-MDR infection. Conclusion  The risk factors identified in our study provide guidance to healthcare workers for the prevention and containment of MDR GNB.

Septic Abortion Secondary to Peptoniphilus asaccharolyticus Complicated by Bacteremia: A Case Report and Review of Literature.

Peptoniphilus species are gram-positive anaerobic coccus (GPAC) that are found in the human flora, such as the skin, gastrointestinal tract, and genitourinary tract, and can be pathogenic. Septic abortion caused by Peptoniphilus species has been reported only three times in the literature. Here, we present a case of Peptoniphilus asaccharolyticus (P. asaccharolyticus) bacteremia as a complication of septic abortion.

Prevalence of Carbapenem-Resistant Enterobacteriaceae in Western Saudi Arabia and Increasing Trends in the Antimicrobial Resistance of Enterobacteriaceae.

PURPOSE:  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. METHODS:  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 1st April 2017 to 30th March 2019. The prevalence of carbapenemase genes ( blaIMP, blaVIM, blaKPC, blaNDM-1, and blaOXA-48) 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: Klebsiella pneumoniae showed a higher frequency of bla OXA-48 (79%) than bla 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. K. pneumoniae was found to be the most frequently isolated causative organism followed by Escherichia coli . The  bla OXA-48 (76.1%) gene was predominant among overall isolates followed by bla NDM (13.9%); both genes coexisted in 6.1% of the isolates. CONCLUSION:  During the study period, the prevalence of CRE considerably rose in the two tertiary care institutions from western Saudi Arabia. In the CRE isolates, bla 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.

The prevalence, risk factors, and complications of Clostridium difficile infection in a tertiary care center, western region, Saudi Arabia.

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.

Molecular epidemiology and outcome of carbapenem-resistant Enterobacterales in Saudi Arabia.

BACKGROUND: The burden of carbapenem resistance is not well studied in the Middle East. We aimed to describe the molecular epidemiology and outcome of carbapenem-resistant Enterobacterales (CRE) infections from several Saudi Arabian Centers. METHODS: This is a multicenter prospective cohort study conducted over a 28-month period. Patients older than 14 years of age with a positive CRE Escherichia coli or Klebsiella pneumoniae culture and a clinically established infection were included in this study. Univariate and multivariable logistic models were constructed to assess the relationship between the outcome of 30-day all-cause mortality and possible continuous and categorical predictor variables. RESULTS: A total of 189 patients were included. The median patient age was 62.8 years and 54.0% were male. The most common CRE infections were nosocomial pneumonia (23.8%) and complicated urinary tract infection (23.8%) and 77 patients (40.7%) had CRE bacteremia. OXA-48 was the most prevalent gene (69.3%). While 100 patients (52.9%) had a clinical cure, 57 patients (30.2%) had died within 30 days and 23 patients (12.2%) relapsed. Univariate analysis to predict 30-day mortality revealed that the following variables are associated with mortality: older age, high Charlson comorbidity index, increased Pitt bacteremia score, nosocomial pneumonia, CRE bacteremia and diabetes mellitus. In multivariable analysis, CRE bacteremia remained as an independent predictor of 30 day all-cause mortality [AOR and 95% CI = 2.81(1.26-6.24), p = 0.01]. CONCLUSIONS: These data highlight the molecular epidemiology and outcomes of CRE infection in Saudi Arabia and will inform future studies to address preventive and management interventions.

Antimicrobial therapy, resistance, and appropriateness in healthcare-associated and community-associated infections; a point prevalence survey.

BACKGROUND: Data examining differences in antimicrobial therapy and its appropriateness between healthcare-associated infections (HAIs) and community-associated infections (CAIs) are limited. The objective was to compare antimicrobial therapy, resistance, and appropriateness between CAIs and HAIs. METHODS: One-day point prevalence survey targeting admitted patients with active infections was conducted in six tertiary care hospitals. Antimicrobial appropriateness was decided based on hospital antimicrobial guidelines, clinical assessment, culture results, and other relevant investigations. RESULTS: Out of 1666 patient records reviewed, 240 (14.4%) infection events were identified. Prevalence of infections treated with antimicrobials were 6.5% for HAIs and 7.1% for CAIs. The most commonly prescribed antimicrobials were carbapenems (19.6%), cephalosporins (14.8%), and vancomycin (13.2%), with some differences between HAIs and CAIs. The overall contribution of MDR pathogens to both HAIs and CAIs was similar (34.0% versus 34.3%, p = 0.969). ESBL was significantly associated with CAIs while other gram-negative MDR pathogens significantly associated with HAIs. Overall appropriateness of antimicrobial therapy was similar in HAI and CAI events (64.2% versus 64.7%, p = 0.934). However, it was highest in aminoglycosides (78.6%) and lowest in vancomycin (40.8%). It was lowest in bloodstream infections than other infections (48.5% versus 61% to 78%, p = 0.044). CONCLUSION: Although the overall burden of MDR pathogens and appropriateness of antimicrobial therapy were similar in HAI and CAI events, there were some differences related to the type of MDR, type of antimicrobials, and type of infection. The current finding can guide training and educational activities of local antimicrobial stewardship initiatives aiming to improve antimicrobial therapy in hospital setting.

Assessing the Effectiveness of Antibiotic Therapy Against Common Gram-Negative Bacteria in a Saudi Arabian Hospital Using the Drug Resistance Index.

INTRODUCTION: Assessing the effectiveness of antibiotics and communicating the problem of resistance are essential when devising antimicrobial stewardship programs (ASPs) in hospital settings. The Drug Resistance Index (DRI) is a useful tool that combines antibiotic consumption and bacterial resistance into a single measure. In this study, we used the DRI to assess the impact of introducing a new antibiotic restriction form on antibiotic effectiveness for the treatment of Gram-negative infections in the intensive care unit (ICU). METHODS: This was an observational study to assess and evaluate the antibiotic susceptibility of Gram-negative bacteria and antibiotic prescribing rates for the antibiotics indicated for Gram-negative bacteria following the introduction of a new antibiotic restriction form. The study was conducted from 2015 to 2017 at King Abdulaziz Medical City, a tertiary care facility in Jeddah, Saudi Arabia. Changes in antibiotic effectiveness before and after the introduction of the form were evaluated by calculating the DRI for four of the most common Gram-negative pathogens and eight commonly used antibiotic classes. RESULTS: The overall DRI for the adult ICU was higher (59.45) in comparison to the hospital-wide DRI (47.96). A higher DRI was evident for carbapenems and antipseudomonal penicillins + beta-lactamase inhibitors. Acinetobacter baumannii had the highest DRI followed by Klebsiella pneumoniae in both the adult ICU and hospital-wide. After the implementation of antibiotic restriction in the adult ICU, the DRI for carbapenems was significantly lower in the post-intervention phase (from 31.61 to 26.05) (p = 0.031). CONCLUSION: The DRI is a useful tool for tracking the effectiveness of antibiotics over time. The results of our study are significant in the way that it highlights the importance of having an effective antibiotic stewardship program in healthcare settings and regular feedback of antibiotic consumption data to the stakeholders to keep the antibiotic prescriptions in check, thereby ensuring their sustained effectiveness.

Melioidosis Pneumonia in Saudi Arabia: A Rare Case Report and Review of the Literature.

Melioidosis is a serious infection caused by the bacterium Burkholderia pseudomallei (B. pseudomallei) mostly found in endemic areas like Southeast Asia and Northern Australia. However, in non-endemic regions, such as Saudi Arabia, it remains somewhat rare and unknown to healthcare workers and the public. Herein, we present a case of melioidosis in a 59-year-old Bangladeshi man who presented with pneumonia. He recently returned from Bangladesh, was a known case of type 2 diabetes on metformin, and presented to the emergency department (ED) with a history of cough, shortness of breath, and fever for three weeks. He was initially misdiagnosed and treated as pulmonary tuberculosis in another hospital prior to his latest presentation. Melioidosis is a severe infection that can be misdiagnosed due to variable presentation and low awareness among healthcare workers of the disease. Diagnosis requires high clinical suspicion, especially in patients who are coming from endemic areas with appropriate risk factors such as diabetes mellitus. Treatment with appropriate antibiotics for a long duration, and outpatient follow-up is vital to reduce the risk of recurrence.

Simultaneous Occurrence of Cytomegalovirus Colitis and Retinitis as the Initial Presentation of Human Immunodeficiency Virus Infection in a Patient With Zero CD4 Count.

Cytomegalovirus (CMV) can be a reason for severe disease in immunocompromised patients, either via the reactivation of latent CMV infection or via the acquisition of primary CMV infection. Clinical syndromes that may be observed are retinitis, colitis, esophagitis, encephalitis, pneumonitis, hepatitis, uveitis, and graft rejection following transplantation. The simultaneous occurrence of CMV colitis and retinitis as the initial presentation of human immunodeficiency virus (HIV) infection is extremely rare. We present a case of a 42-year-old male, known to have type 2 diabetes, bronchial asthma, and allergic rhinitis, who presented to the emergency department (ED) with two weeks history of abdominal pain and watery diarrhea four to five times per day sometimes accompanied by small amounts of blood. He also had an on-and-off subjective fever for the last two months prior to presentation, loss of appetite, and weight loss of 13 kg over the last six months. Additionally, he had a history of travel outside Saudi Arabia and unprotected sex. HIV-1 serology (combination antigen/antibody immunoassay) was requested, which came out positive, with a viral load of 323141 copies/mL and decreased CD4+ T lymphocytes (0 cel/µL). CMV polymerase chain reaction (PCR) quantitative was detected and the CMV viral load was 694963 IU/mL. Given the patient's bloody diarrhea with positive CMV and HIV, the gastroenterology team was consulted and they decided to proceed with a colonoscopy and biopsy. The patient was diagnosed with CMV colitis based on the biopsy results. The patient also was found to have CMV retinitis based on ophthalmologic assessment. Multidisciplinary teams, including infectious diseases, gastroenterology, ophthalmology, and pathology, should cooperate to facilitate an accurate and fast diagnosis. Further complications can be prevented by early diagnosis andtreatment.

Favipiravir and Hydroxychloroquine Combination Therapy in Patients with Moderate to Severe COVID-19 (FACCT Trial): An Open-Label, Multicenter, Randomized, Controlled Trial.

INTRODUCTION: Antiviral drugs have shown limited effectiveness in treating patients with coronavirus disease 2019 (COVID-19). We aimed to assess the effects of a favipiravir and hydroxychloroquine combination on treating moderate-to-severe COVID-19 patients. METHODS: An investigator-initiated, multicenter, open-label, randomized trial at nine hospitals. Eligible patients were adults with moderate-to-severe COVID-19 defined as oxygen saturation (SaO2) of ≤ 94% while breathing ambient air or significant clinical symptoms with chest x-ray changes requiring hospital admission. Randomization was in a 1:1 ratio to receive standard care (control group) or standard care plus favipiravir and hydroxychloroquine. The primary outcome was time to clinical improvement of two points (from the status at randomization) on a seven-category ordinal scale or live discharge from the hospital within 14 days. Analyses were done in an intention-to-treat population. RESULTS: From May 2020 to Jan 2021, 254 patients were enrolled; 129 were assigned to standard of care and 125 to the treatment. The mean age was 52 (± 13) years, and 103 (41%) were women. At randomization, six patients were on invasive mechanical ventilation, 229 (90.15%) were requiring supplemental oxygen only (with or without non-invasive ventilation), and 19 (7.48%) were receiving neither. The time to clinical improvement was not significantly different between the groups: median of 9 days in the treatment group and 7 days in the control group (HR: 0.845; 95% CI 0.617-1.157; p-value = 0.29). The 28-day mortality was not significantly different between the groups (7.63% treatment) vs. (10.32% control); p-value = 0.45. The most prevalent adverse events were headache, elevation in ALT, and the prolonged QTc interval in the treatment group. CONCLUSION: The combination of favipiravir and hydroxychloroquine did not result in a statistically significant clinical benefit in patients with moderate-to-severe COVID-19. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov (NCT04392973).

Molecular Detection of Influenza A and B Viruses in Four Consecutive Influenza Seasons 2015-16 to 2018-19 in a Tertiary Center in Western Saudi Arabia.

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.

The Burden of Invasive Vaccine-Preventable Diseases in Adults in the Middle East and North Africa (MENA) Region.

Implementing vaccination programmes at the national level is key to managing vaccine-preventable diseases (VPDs) in the overall population. Although paediatric immunization programmes have significantly reduced the burden of VPD, disease burden in adults still poses a substantial challenge, particularly in low- and middle-income countries such as those within the Middle East and North Africa (MENA) region. Invasive bacterial diseases (IBDs) are an important public health concern within this region, although vaccines are available to prevent the three most common causative organisms associated with IBD: Neisseria meningitidis (NM), Streptococcus pneumoniae (SP), and Haemophilus influenzae (HI). For this review, three separate PubMed searches were used to identify English-language publications describing the epidemiology of NM, SP, and HI in adults within the MENA region. Of the 161 total publications retrieved among all 3 literature searches, 39 were included in this review (NM: 8 publications; SP: 27 publications; HI: 4 publications). Publications describing epidemiology in paediatric or overall populations were excluded. Overall, these studies generally observed a high burden of IBD among adults in this region. Although NM, SP, and HI are communicable diseases in several countries, the surveillance systems in the MENA region are largely inadequate, resulting in poor responses to outbreaks and hindering improvement in outcomes of communicable diseases. Improving IBD surveillance would provide necessary estimates of disease burden, resulting in better vaccination strategies and improved outcomes. In conclusion, the present review provides a summary of the available information on the epidemiology of vaccine-preventable IBD in adults within the MENA region and highlights the need for increased disease surveillance and preventive strategies in these countries.

Dengue-Induced Hemophagocytic Lymphohistiocytosis: A Case Report and Literature Review.

Hemophagocytic lymphohistiocytosis (HLH) is an uncommon fatal disease of otherwise normal but hyperactive lymphocytes and histocytes. HLH could be primary (hereditary) or secondary (acquired). Fever, hepatosplenomegaly, lymphadenopathy, and neurologic dysfunction are among the common symptoms of HLH. The diagnosis of HLH is based on clinical and biochemical findings. We report here a case of a patient infected with the dengue virus who developed HLH during hospitalization. A 63-year-old female known case of asthma on inhalers, chronic hepatitis B virus, gastritis on proton pump inhibitors, and hemoglobin H disease presented to the emergency department (ED) with a history of high-grade fever (highest recorded temperature 40° C/ 104° F), which was relieved partially by antipyretics, generalized fatigability, body aches, headache and mosquito bites for four days. The physical examination was significant for hepatomegaly of 4 cm below the right costal margin. Investigations revealed pancytopenia with elevated ferritin levels (> 40000 µg/L). Viral serology was positive for dengue NS1 antigen. After hematology consultation, a bone marrow biopsy was done, which showed trilineage hematopoiesis with increased histiocytes and occasional hemophagocytosis. Given that the patient was clinically stable and there was a clear triggering condition, we opted for supportive measures rather than HLH-specific therapy. The patient was given 2 units packed red blood cells for anemia. On the following days, the patient has no recurrence of fever, with marked improvement in the biochemical profile including ferritin level (1165 µg/L). HLH is a deleterious disease with a high fatality rate, which requires the clinician to have a low threshold for suspicion in the differentials of children and adults with symptoms of persistent fever, hepatosplenomegaly, and cytopenia. Dengue-associated HLH diagnosis is challenging, but it is very important to be recognized, as early recognition is associated with better outcomes. Physicians must work in collaboration with pathologists and microbiologists for the proper diagnosis.

The economic burden of dengue fever in the Kingdom of Saudi Arabia.

Rapid urbanization, global trade, and the exceptionally great numbers of worldwide visitors during Hajj and Umrah have all placed the Kingdom of Saudi Arabia at a significant risk of introducing several vector-borne tropical diseases, such as dengue fever virus (DENV) infection. In this study we estimated DENV infection cost of illness (COI) in Saudi Arabia in the period 2013-2017, by processing national data including all declared cases recorded in referral centers in the western region, being the endemic region of the country. Using a statistically validated predictive model that was built on a representative sample of 717 laboratory-confirmed cases of DENV infection, direct costs, due to care-related expenditures, were estimated by applying the predictive equation to national data. However, indirect costs, which are due to productivity loss, were estimated using the human capital model based on gross domestic product adjusted for invalidity duration. Further, under-reporting was adjusted by using an expansion factor EF = 3. We observed highest estimated costs in 2016 with over US$168.5 Million total costs, including direct (US$29.0 Million) and indirect (US$139.5 Million) costs, for a total 4415 confirmed cases. The total DENV COI for the five years was estimated as US$551.0 Million for a total 15,369 patients (59.7%) out of 25,745 declared cases, resulting in an average cost of US$11 947.6 by patient. Depending on the year, productivity years loss costs accounted for 63.3% to 83.8% of the estimated total costs. Dengue has a substantial local economic burden that costs US$110.2 Million per year, stressing the urgent need for an effective national prevention strategy to perform considerable cost-savings besides reducing morbidity.

First report of Klebsiella quasipneumoniae harboring blaKPC-2 in Saudi Arabia.

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 blaKPC-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 blaKPC-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 blaKPC-2 gene, flanked by transposable elements (ISKpn6-blaKPC-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.

Treatment patterns, resource utilization, and outcomes among hospitalized patients with methicillin-resistant Staphylococcus aureus complicated skin and soft tissue infections in Lebanon and Saudi Arabia.

OBJECTIVES: To describe treatment patterns and medical resource use for methicillin-resistant Staphylococcus aureus (MRSA) complicated skin and soft tissue infections (cSSTI) in Saudi Arabia and Lebanon in terms of drug selection against the infecting pathogen as well as hospital resource utilization and clinical outcomes among patients with these infections. METHODS: This retrospective chart review study evaluated 2011-2012 data from five hospitals in Saudi Arabia and Lebanon. Patients were included if they had been discharged with a diagnosis of MRSA cSSTI, which was culture-proven or suspected based on clinical criteria. Hospital data were abstracted for a random sample of patients with each infection type to capture demographics, treatment patterns, hospital resource utilization, and clinical outcomes. Statistical analysis was descriptive. RESULTS: Data were abstracted from medical records of 87 patients with MRSA cSSTI; mean age 52.4±25.9 years and 61% male. Only 64% of patients received an MRSA active initial therapy, with 56% of first-line regimens containing older beta-lactams. The mean total length of stay was 26.3 days, with the majority (19.1 days) spent in general wards. Surgical procedures included incision and drainage (22% of patients), debridement (14%), and amputation (5%). Mechanical ventilation was required by 9% of patients, with a mean duration of 18 days per patient. Hemodialysis was required by four patients (5%), two of whom were reported to have moderate to severe renal disease on admission, for a mean of 5.5 days. Inpatient mortality was 8%. Thirty-nine percent were prescribed at least one antibiotic at discharge, with the most commonly prescribed discharge antibiotics being clindamycin (44%), ciprofloxacin (18%), trimethoprim/sulfamethoxazole (12%), and linezolid (9%). CONCLUSION: This Middle Eastern real-world study of resource use and treatment patterns in MRSA cSSTI indicates that management of this condition could be further optimized in terms of drug selection and resource utilization.