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Zuluaga A.F.,GRIPE Grupo Investigador de Problemas en Enfermedades Infecciosas | Agudelo M.,GRIPE Grupo Investigador de Problemas en Enfermedades Infecciosas | Rodriguez C.A.,GRIPE Grupo Investigador de Problemas en Enfermedades Infecciosas | Vesga O.,GRIPE Grupo Investigador de Problemas en Enfermedades Infecciosas | Vesga O.,University of Antioquia
Journal of Biomedical Science | Year: 2015

Background: Experimental models of pneumonia with penicillin non-susceptible Streptococcus pneumoniae (PNSSP) are hard to reproduce because the majority of strains with clinical relevance (like serotypes 6B, 9 V and 19 F) have low murine virulence. By optimization of culture and inoculum conditions of PNSSP (using porcine mucin), our aim was to develop a suitable, reliable and reproducible pneumonia mouse model for anti-infective pharmacology research. Results: Seven PNSSP strains, including serotypes 6B, 9 V, 14 and 19 F were included. Strain INS-E611 displayed the highest murine virulence and was chosen to validate the lung model. Nose-instilled pneumococci grew between 2.1 and 2.5 log10 CFU/g of lung in 24 hours when an optimized culture of bacterial cells was used, but animals were all alive and recovered of infection after 36 h. In contrast, inoculum supplementation with mucin led to 100% mortality related to a successful lung infection confirmed by histopathology. These findings were reproduced with all seven PNSSP strains in neutropenic mice. Immunocompetent animals cleared all strains spontaneously. Conclusions: This pneumonia model produces a progressive and uniformly fatal lung infection with diverse serotypes of PNSSP independently of their intrinsic murine virulence. © 2015 Zuluaga et al.; licensee BioMed Central. Source


Rodriguez C.A.,GRIPE Grupo Investigador de Problemas en Enfermedades Infecciosas | Agudelo M.,GRIPE Grupo Investigador de Problemas en Enfermedades Infecciosas | Agudelo M.,University of Antioquia | Gonzalez J.M.,GRIPE Grupo Investigador de Problemas en Enfermedades Infecciosas | And 4 more authors.
Antimicrobial Agents and Chemotherapy | Year: 2015

Negligible in vivo growth of enterococci and high-level dispersion of data have led to inaccurate estimations of antibiotic pharmacodynamics (PD). Here we improved an in vivo model apt for PD studies by optimizing the in vitro culture conditions for enterococci. The PD of vancomycin (VAN), ampicillin-sulbactam (SAM), and piperacillin-tazobactam (TZP) against enterococci were determined in vivo, comparing the following different conditions of inoculum preparation: aerobiosis, aerobiosis plus mucin, and anaerobiosis plus mucin. Drug exposure was expressed as the ratio of the area under the concentration-time curve for the free, unbound fraction of the drug to the MIC ( fAUC/MIC) (VAN) or the time in a 24-h period that the drug concentration for the free, unbound fraction exceeded the MIC under steady-state pharmacokinetic conditions (fT>MIC) (SAM and TZP) and linked to the change in log10 CFU/thigh. Only anaerobiosis plus mucin enhanced the in vivo growth, yielding significant PD parameters with all antibiotics. In conclusion, robust in vivo growth of enterococci was crucial for better determining the PD of tested antibacterial agents, and this was achieved by optimizing the procedure for preparing the inoculum. © 2015, American Society for Microbiology. All Rights Reserved. Source

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