Evaluating the antimicrobial efficacy of ceftriaxone regimens: 1 g twice daily versus 2 g once daily in a murine model of Streptococcus pneumoniae pneumonia

Abstract

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 (Δlog10 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 Δlog10 cfu/lungs versus −3.47 ± 0.17 Δlog10 cfu/lungs, P < 0.001; 2 mg/L, −3.41 ± 0.31 Δ log10 cfu/lungs versus −2.71 ± 0.37 Δlog10 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 Δlog10 cfu/lungs versus −0.42 ± 0.37 Δlog10 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.