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Beta-lactam modification of the bacteraemic profile and its relationship with mortality in a pneumococcal mouse
1Centro Nacional de Microbiología, Instituto de Salud Carlos III, Ctra. Majadahonda-Pozuelo, Km. 2, 28220 Majadahonda, Madrid, Spain.
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 x 10(7) 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.
Insights
High bacterial load in the blood of mice with sepsis significantly increases mortality risk. Amoxicillin demonstrated higher survival rates than cefotaxime in this Streptococcus pneumoniae infection model.
Area of Science:
- Microbiology
- Pharmacology
- Infectious Diseases
Background:
- Sepsis remains a major global health challenge, often caused by bacterial infections.
- Streptococcus pneumoniae serotype 6B is a significant pathogen, necessitating effective antimicrobial strategies.
- Understanding the relationship between bacterial load and mortality is crucial for sepsis management.
Purpose of the Study:
- To investigate the correlation between the bacteraemic profile and mortality in a murine sepsis model.
- To evaluate the efficacy of amoxicillin and cefotaxime against a clinical isolate of Streptococcus pneumoniae serotype 6B.
Main Methods:
- A sepsis model was established in BALB/c mice using Streptococcus pneumoniae serotype 6B.
- Animals received varying doses of amoxicillin or cefotaxime subcutaneously for 48 hours.
- Blood cultures were performed daily for 15 days to monitor bacteraemia.
- Survival rates were recorded and analyzed in relation to bacterial load.
Main Results:
- Amoxicillin achieved a 100% survival rate at 25 mg/kg, while cefotaxime yielded 60% survival at 50 mg/kg.
- A statistically significant relationship (P = 0.012) was observed between peak blood bacterial concentration (cfu/mL) and mortality.
- A maximum bacterial load of 6.5 log cfu/mL was associated with an 84% probability of death.
Conclusions:
- The bacterial load in the bloodstream is a critical predictor of mortality in this Streptococcus pneumoniae sepsis model.
- Amoxicillin exhibited superior efficacy compared to cefotaxime in improving survival rates.
- These findings underscore the importance of early bacterial load assessment and prompt, effective antibiotic treatment in sepsis.