Abstract
BACKGROUND: Ceftriaxone is administered in regimens of either 2 g once-daily or 1 g twice-daily for the treatment of pneumonia caused by Streptococcus pneumoniae. Previous clinical study suggests the 2 g once-daily regimen is more effective, but comparison of antimicrobial efficacy between are lacking. OBJECTIVES: To assess the antimicrobial efficacy of these two ceftriaxone regimens against S. pneumoniae using a murine model of pneumonia. METHODS: The study employed three S. pneumoniae isolates with ceftriaxone MICs of 1, 2 and 4 mg/L and two human-simulated regimens based on the blood concentration of ceftriaxone (1 g twice-daily and 2 g once-daily). Antimicrobial activity was quantified based on the change in bacterial counts (Δlog(10) cfu/lungs) observed in treated mice after 24 h, relative to the control mice at 0 h. RESULTS: The human-simulated 2 g once-daily regimen of ceftriaxone exhibited significantly higher antimicrobial activity against S. pneumoniae isolates with MICs of 1 and 2 mg/L compared with the 1 g twice-daily regimen (1 mg/L, -5.14 ± 0.19 Δlog(10) cfu/lungs versus -3.47 ± 0.17 Δlog(10) cfu/lungs, P < 0.001; 2 mg/L, -3.41 ± 0.31 Δ log(10) cfu/lungs versus -2.71 ± 0.37 Δlog(10) cfu/lungs, P = 0.027). No significant difference in antimicrobial activity was observed against the S. pneumoniae isolate with a MIC of 4 mg/L between the two regimens (-0.33 ± 0.18 Δlog(10) cfu/lungs versus -0.42 ± 0.37 Δlog(10) cfu/lungs, P = 0.684). CONCLUSION: 2 g once-daily regimen of ceftriaxone is more effective for treating pneumonia caused by S. pneumoniae, with MICs of ≤2 mg/L.