Generic Vancomycin Enriches Resistant Subpopulations of Staphylococcus aureus after Exposure in a Neutropenic Mouse Thigh Infection Model

ABSTRACT: Previous studies have shown that “bioequivalent” generic products of vancomycin are less effective in vivo against Staphylococcus aureus than the innovator compound. Considering that suboptimal bactericidal effect has been associated withemergence of resistance, we aimed to assess in vivo the impact of exposure to innovator and generic products of vancomycin on S. aureus susceptibility. A clinical methicillin-resistant S. aureus (MRSA) strain from a liver transplant patient withpersistent bacteremia was used for which MIC, minimum bactericidal concentration (MBC), and autolytic properties weredetermined. Susceptibility was also assessed by determining a population analysis profile (PAP) with vancomycin concentrations from 0 to 5 mg/liter. ICR neutropenic mice were inoculated in each thigh with 7.0 log10 CFU. Treatment with thedifferent vancomycin products (innovator and three generics; 1,200 mg/kg of body weight/day every 3 h) started 2 h laterwhile the control group received sterile saline. After 24 h, mice were euthanized, and the thigh homogenates were plated.Recovered colonies were reinoculated to new groups of animals, and the exposure-recovery process was repeated until 12cycles were completed. The evolution of resistance was assessed by PAP after cycles 5, 10, 11, and 12. The initial isolate displayed reduced autolysis and higher resistance frequencies than S. aureus ATCC 29213 but without vancomycinintermediate S. aureus (VISA) subpopulations. After 12 cycles, innovator vancomycin had significantly reduced resistantsubpopulations at 1, 2, and 3 mg/liter, while the generic products had enriched them progressively by orders of magnitude.The great capacity of generic vancomycin to select for less susceptible organisms raises concerns about the role of therapeutic inequivalence of any antimicrobial on the epidemiology of resistance worldwide  

• Autores: Rodríguez Jaramillo, Carlos Andrés; Agudelo Pérez, María; Zuluaga Salazar, Andres Felipe; Vesga Meneses, Omar
• Tipo de recurso: Article of investigation
• Fecha de publicación: 2011
• Institución: Universidad de Antioquia
• Repositorio: Repositorio UdeA
• Idioma: eng
• OAI Identifier: oai:bibliotecadigital.udea.edu.co:10495/26354
• Acceso en línea: http://hdl.handle.net/10495/26354
• Palabra clave: Vancomicina; Vancomycin; Medicamentos Genéricos; Drugs, Generic; Esquema de Medicación; Drug Administration Schedule; Modelos Animales de Enfermedad; Disease Models, Animal; Staphylococcus aureus Resistente a Meticilina; Methicillin-Resistant Staphylococcus aureus
• Rights: openAccess
• License: http://purl.org/coar/access_right/c_abf2