Caracterização molecular da virulência e perfil de resistência antimicrobiana de cepas de shigella spp isoladas de crianças com diarreia moderada a severa na cidade de Fortaleza-Ce, Brasil

Abstract

Shigellosis is a major public health problem worldwide, mainly in children from developing countries, due to high clinical severity, lack of vaccine and high rates of antimicrobial resistance. The study aimed to perform molecular characterization of virulence and antimicrobial resistance description of Shigella sp. strains isolated from children with diarrhea in Fortaleza, Ceará, Brazil. 63 Shigella spp. strains were isolated from stool children samples with moderate to severe diarrhea between 2008 and 2009 in Fortaleza.Socioeconomic and clinical data was collected through a standardized questionnaire. Microbiological characterization and immunoagglutination assay were performed for serogroups classification (S. flexneri, S. sonnei, S. dysenteriae and S. boydii). Genetic material was extracted and analyzed by four multiple polymerase chain reactions, detecting 16 virulence genes. Antimicrobial susceptibility tests were performed using Kirby-Bauer disk diffusion method, with a panel of 13 antimicrobials. A majority of S. flexneri (43%) and S. sonnei (43%) was observed, followed by S. dysenteriae (8%) and S. boydii (6%).S. flexneri was associated with family incomes below the minimum wage and with higher number of virulence genes detected. The virulence genes pic (protein associated with adhesion to intestinal mucosa), set (enterotoxin 1) and sepA (protein involved with cell invasion) were separately associated with S. flexneri. The presence of the sepA gene was associated with more intense abdominal pain. The resistant phenotype to at least one drug was observed in 96.8% of the isolates. The higher resistance rates were against sulfamethoxazol/trimethoprim combination (82.5%), followed by tetracyclin (79.4%), ampicilin (60.3%) and chloramphenicol (47.6%). S. flexneri was associated with resistance to ampicilin and to chloramphenicol, while S. sonnei was associated with resistance to azitromicin. Resistance to three or more antimicrobial was associated with S. flexneri. The presence of pic, set e sepAgenes was associated with resistance to at least three antimicrobials. Strains harboring higher number of virulence genes were associated with resistance to more antimicrobials. In conclusion, shigellosis in children from Fortaleza has major and similar proportions ofS. sonnei andS. flexneri.In addition, the former is associated with increased disease severity, lower socioeconomic level, higher number of virulence genes, the concomitant presence of pic, set e sepAgenes and resistance to three or more antimicrobials. This study suggests a potential socioeconomic transition of the population and alerts for the resistance to commonly prescribed antimicrobials. Moreover, resistance to some antimicrobials can be Shigellaserogroup-specific and is associated with higher bacterial virulence.