β-lactam modification of the bacteraemic profile and its relationship with mortality in a pneumococcal mouse sepsis model

Abstract

A sepsis BALB/c mice model was used to investigate the relationship between mortality and the bacteraemic profile produced by a serotype 6B Streptococcus pneumoniae clinical isolate (MIC/MBC of amoxicillin 4/4 mg/L and of cefotaxime 2/4 mg/L). Animals were treated subcutaneously with doses of amoxicillin or cefotaxime ranging from 6.25 to 50 mg/kg tds for 48 h, starting 1 h after intraperitoneal inoculation (2 × 107 cfu/mouse). Blood cultures were carried out daily over 15 days. A survival rate of 100% was obtained with amoxicillin 25 mg/kg and of 60% with cefotaxime 50 mg/kg. A statistically significant (P = 0.012) relationship was found between the maximum cfu/mL in blood and mortality. A maximum log cfu/mL of 6.5 was associated with an 84% probability of death.