Mazen Zaylaa

Background and Aims: Antimicrobial resistance (AMR) in Enterobacteriaceae poses a critical threat to global health, particularly in regions where antibiotic misuse and limited surveillance prevail. Intensive care units (ICUs) act as focal points for resistance emergence and dissemination. This study aimed to evaluate long‐term resistance trends among clinically significant Enterobacteriaceae isolated from two hospitals in North Lebanon (2016–2024). Methods: A retrospective analysis was conducted on 14,013 Enterobacteriaceae isolates obtained from Al Monla and Dar Al Shifa hospitals between 2016 and 2024. Identification was achieved using biochemical testing or MALDI‐TOF mass spectrometry, and susceptibility testing followed EUCAST standards. No molecular characterization of resistance genes was performed. Data were analyzed using SPSS v23.0, applying Chi‐square or Fisher's exact tests ( p < 0.05). Results: Among 14,013 isolates, Escherichia coli ( E. coli ) was predominant (66.4%), followed by Klebsiella pneumoniae ( K. pneumoniae ) (12.4%), Proteus mirabilis ( P. mirabilis ) (5.5%), and Enterobacter cloacae ( E. cloacae ) (3.7%). Overall, β‐lactam resistance remained widespread across species. In E. coli , carbapenem non‐susceptibility increased from 2.7% to 4.8% ( p < 0.001). P. mirabilis and E. cloacae exhibited significant increases in ESBL production ( p = 0.006 and p = 0.007, respectively). K. pneumoniae showed fluctuating resistance trends with a mild decline in carbapenem resistance ( p = 0.029). ICU isolates demonstrated higher ESBL and MDR rates than non‐ICU isolates ( p < 0.01), and hospital‐acquired infections showed significantly higher resistance across most drug classes compared to community‐acquired cases ( p < 0.05). Conclusion: Over the 9‐year study period, Enterobacteriaceae isolates in North Lebanon demonstrated persistently high β‐lactam resistance and increasing carbapenem non‐susceptibility, particularly in E. coli . These findings underscore the importance of ongoing AMR surveillance and provide regional data that may support future evidence‐based clinical and public health decision‐making.

Klebsiella pneumoniae ( K. pneumoniae ) is a major cause of urinary tract infections (UTIs) and poses a growing public health concern due to multidrug resistance and virulence potential. This study aimed to characterize antimicrobial resistance, biofilm formation, and virulence gene distribution among urinary K. pneumoniae isolates from North Lebanon and to explore correlations between these factors. A total of 153 non‐duplicate isolates from hospital and community settings were analyzed for antibiotic susceptibility, hypermucoviscosity, biofilm formation, and presence of key virulence (fimH, mrkD, magA, rmpA, entB, iucA, iroN, kfu) and β‐lactamase (blaTEM, blaSHV, blaCTX‐M) genes. Adhesion‐associated genes fimH and mrkD were highly prevalent, particularly in hospital‐acquired and strong biofilm‐producing isolates. Capsular and regulatory genes (magA) was more frequent in putative hypervirulent and community‐acquired strains, while siderophore genes entB and iucA were strongly associated with biofilm formation and hospital‐acquired infections. A significantly higher resistance to cephalosporins, along with an increased frequency of multidrug‐resistant phenotypes, was detected in hospital‐acquired, classical, and strong biofilm‐forming isolates. ESBL production was significantly more common in hospital‐acquired and biofilm‐forming isolates. Strong biofilm formation was largely associated with classical K. pneumoniae and hospital‐acquired infections, whereas putative hypervirulent strains were primarily weak biofilm producers and community‐acquired. These findings highlight the interplay between virulence determinants, biofilm formation, and antibiotic resistance, emphasizing the need for targeted infection control and treatment strategies in North Lebanon.

Les maladies inflammatoires chroniques de l’intestin (MICI), qui comprennent les deux principales formes, la maladie de Crohn (MC) et la rectocolite hémorragique (RCH), sont caractérisées par une inflammation chronique et récurrente de la muqueuse intestinale, ayant un impact considérable sur la qualité de vie. À l'heure actuelle, la prise en charge thérapeutique de la MC n'est pas curative et un tiers des patients ne réagissent pas aux traitements biologiques et aux immunosuppresseurs. Par conséquent, de nouvelles stratégies pour traiter cette maladie sont fortement attendues. La dérégulation de l'interaction entre d'une part les facteurs génétiques et le système immunitaire de l'hôte, et d'autre part le microbiote intestinal et les facteurs environnementaux, est impliquée dans le développement des MICI. Cette perturbation entraîne effectivement une augmentation de la perméabilité intestinale et une inflammation persistante. Restaurer le microbiote «dysbiotique» et les fonctions intestinales altérées représentent donc une thérapeutique alternative intéressante. De ce fait, les probiotiques sont une option intéressante et ont été utilisés avec succès chez des patients souffrant de pouchite et de RCH. Cependant, leur effet protecteur est clairement souche-dépendant et plusieurs souches probiotiques bien connues n’ont pu conduire à un résultat clinique probant, en particulier chez les patients souffrant de MC. Le décryptage des mécanismes moléculaires sera donc la clé pour permettre une recommandation efficace des probiotiques dans le traitement ou la prévention des MICI. La sélection de souches basée sur des critères de sélection bien définis et en utilisant des modèles bien maitrisés est indispensable à ce processus. L'objectif principal de cette thèse était de sélectionner des lactobacilles et des bifidobactéries parmi une collection de souches françaises et libanaises, capables de présenter des propriétés protectrices contre les MICI, en se concentrant sur leurs capacités immuno-régulatrices et leurs capacités à renforcer la barrière épithéliale. Des approches in vitro ont été utilisées pour sélectionner des souches ayant une activité anti-inflammatoire et également capables d'améliorer la fonction de la barrière intestinale. Cinq souches ont été identifiées présentant des caractéristiques différentes, mais avec un potentiel thérapeutique élevé. Deux souches se sont révélées hautement protectrices dans deux modèles différents de colite aiguë et de colite de bas grade. Nos résultats ont confirmé en outre l'hypothèse selon laquelle la capacité des souches à atténuer l'inflammation est en partie due à l'amélioration de la barrière intestinale et à la restauration des protéines de jonction serrés.Un nombre croissant d’études génétiques ont prouvé que l’autophagie peut affecter plusieurs aspects de la réponse immunitaire des muqueuses, notamment via l’élimination de bactéries intracellulaires, la sécrétion de peptides antimicrobiens, la production de cytokines pro-inflammatoires et la présentation des antigènes. Par conséquent, l'autophagie peut être considérée comme un mécanisme de régulation clé impliqué dans la physiopathologie de la MC. Nous avons donc évalué la capacité des souches à activer cette voie et montré que les souches sélectionnées étaient en effet capables d’induire une activation de l’autophagie dans des cellules dendritiques murines. Nous avons démontré in vitro que le blocage de l'autophagie pouvait diminuer la capacité des souches à induire la sécrétion d'IL-10, cytokine anti-inflammatoire et, inversement, à exacerber la sécrétion d'IL-1β, cytokine pro-inflammatoire. Nous avons pu confirmer, à l'aide d'un modèle murin de colite, que la capacité protectrice d’une souche impliquait la machinerie autophagique, et nous avons pu mettre en évidence le rôle des cellules dendritiques dans ce processus

Background: Autism spectrum disorder (ASD) is defined by persistent social communication difficulties and restricted, repetitive behaviours. Its increasing prevalence heightens the demand for earlier diagnosis and intervention. ASD can be diagnosed between 18 and 24 months, the typical kindergarten entry age, highlighting the vital role of kindergarten teachers in early detection. In Lebanon, the economic crisis has increased the demand for kindergarten services as both parents are working. This study aims to assess the knowledge of kindergarten teachers in Lebanon about ASD, emphasising their role in early detection and intervention referral. Methods: A descriptive cross-sectional study was conducted between June 2023 and January 2024 using convenience sampling. Data were collected through a survey administered to 355 kindergarten teachers from all Lebanese governorates. The questionnaire assessed participants’ sociodemographic characteristics, perceived knowledge of ASD and included the validated Autism Spectrum Knowledge Scale—General. Results: Responses were obtained from 355 kindergarten teachers, aged 18 to 50 years, representing 57 kindergartens. Overall, Lebanese kindergarten teachers demonstrated moderate knowledge of ASD, with a mean score of 17.7/32 (55.3%). The level of knowledge regarding the symptoms and associated behaviours, assessment and diagnosis, treatment, outcomes and prognosis of the disease was moderate (59.9%, 58.2%, 54.3% and 52%, respectively). The lowest scores were observed in items related to the aetiology and prevalence of ASD (48.3%). Moreover, areas of residence, years of experience, sources of information and prior interactions with children with ASD were all statistically significant predictors of ASD knowledge (p=0.046, p=0.002, p=0.043 and p<0.001, respectively). Multivariate linear regression revealed that area of residence (p=0.009) and prior interaction with children with ASD (p<0.001) were significantly associated with knowledge scores. Conclusions: Many teachers are unfamiliar with ASD and its implications for children, yet it is crucial to raise awareness of ASD and incorporate it into educational curricula.

Background: The nasopharyngeal carriage of Streptococcus pneumoniae can be the source of transmission between humans and the starting step towards invasive pneumococcal diseases. Data on the carriage of pneumococci in children before and after the pneumococcal conjugate vaccines (PCV) integration in a country are essential for monitoring any change in pneumococcal carriage serotypes and their antimicrobial-resistance profiles. Methods: We investigated the epidemiology of S. pneumoniae carriage among children younger than five years old in Tripoli, Lebanon, in 2016, the same year of integration of PCV13 in the country’s Expanded Program on Immunization. Results: Of 104 participating children, 57 (54.8%) gave a positive culture for S. pneumoniae. Antimicrobial susceptibility testing revealed that 26.3% of isolates were multidrug-resistant. Resistance was detected mainly against oxacillin (77.2%), tetracycline (29.8%), erythromycin (22.8%), trimethoprim-sulfamethoxazole (22.8%), clindamycin (19.3%), minocycline (19.3%), and teicoplanin (1.8%). Serotyping analysis identified 14 distinct serotypes, with only 31.3% and 50% of isolates corresponding to vaccine serotypes covered by PCV13 and PCV20, respectively. The most common serotypes were 11A, 19F, 23A, and those of serogroup 24 (Sg24) accounted for 37.5% of the serotyped isolates. Conclusions: Our findings have revealed the circulation of a pool of pneumococci isolates with high levels of antibiotic resistance and different degrees of likelihood of causing invasive diseases in children under five years old in Tripoli in 2016. The overall limited PCV13 vaccine coverage in this study highlighted the need for vaccines with greater coverage in the immunization programs in Lebanon. Longitudinal national studies investigating the carriage of pneumococci in children are required to further assess the impact of the PCV vaccine on pneumococci carriage in children and steer new vaccine development.