在肺炎链球菌肺炎小鼠模型中评估头孢曲松方案的抗菌疗效:每天两次,每次 1 克与每天一次,每次 2 克。

IF 3.7 Q2 INFECTIOUS DISEASES JAC-Antimicrobial Resistance Pub Date : 2024-06-04 eCollection Date: 2024-06-01 DOI:10.1093/jacamr/dlae092
Hideo Kato, Mao Hagihara, Shun-Ichi Hiramatsu, Hiroyuki Suematsu, Naoya Nishiyama, Nobuhiro Asai, Hiroshige Mikamo, Kazuko Yamamoto, Takuya Iwamoto
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Previous clinical study suggests the 2 g once-daily regimen is more effective, but comparison of antimicrobial efficacy between are lacking.</p><p><strong>Objectives: </strong>To assess the antimicrobial efficacy of these two ceftriaxone regimens against <i>S. pneumoniae</i> using a murine model of pneumonia.</p><p><strong>Methods: </strong>The study employed three <i>S. pneumoniae</i> 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<sub>10</sub> cfu/lungs) observed in treated mice after 24 h, relative to the control mice at 0 h.</p><p><strong>Results: </strong>The human-simulated 2 g once-daily regimen of ceftriaxone exhibited significantly higher antimicrobial activity against <i>S. pneumoniae</i> 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<sub>10</sub> cfu/lungs versus -3.47 ± 0.17 Δlog<sub>10</sub> cfu/lungs, <i>P</i> < 0.001; 2 mg/L, -3.41 ± 0.31 Δ log<sub>10</sub> cfu/lungs versus -2.71 ± 0.37 Δlog<sub>10</sub> cfu/lungs, <i>P</i> = 0.027). 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引用次数: 0

摘要

背景:头孢曲松用于治疗由肺炎链球菌引起的肺炎,治疗方案为每日一次 2 克或每日两次 1 克。以往的临床研究表明,每天一次、每次 2 克的方案更为有效,但目前还缺乏两者抗菌效果的比较:利用小鼠肺炎模型评估这两种头孢曲松方案对肺炎双球菌的抗菌效果:研究采用了头孢曲松 MIC 值为 1、2 和 4 mg/L的三种肺炎链球菌分离株,以及两种基于头孢曲松血药浓度的人体模拟方案(1 克,每日两次;2 克,每日一次)。抗菌活性根据治疗小鼠 24 小时后观察到的细菌计数(Δlog10 cfu/lungs)相对于 0 小时对照小鼠的变化进行量化:结果:与每天两次、每次 1 克的头孢曲松治疗方案相比,每天一次、每次 2 克的头孢曲松治疗方案对肺炎双球菌分离株的抗菌活性明显更高(1 毫克/升,-5.14 ± 0.19 Δlog10 cfu/lungs 对 -3.47 ± 0.17 Δlog10 cfu/lungs,P 10 cfu/lungs 对 -2.71 ± 0.37 Δlog10 cfu/lungs,P = 0.027)。两种方案对 MIC 值为 4 mg/L 的肺炎双球菌分离株的抗菌活性无明显差异(-0.33 ± 0.18 Δlog10 cfu/lungs 对 -0.42 ± 0.37 Δlog10 cfu/lungs,P = 0.684)。
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Evaluating the antimicrobial efficacy of ceftriaxone regimens: 1 g twice daily versus 2 g once daily in a murine model of Streptococcus pneumoniae pneumonia.

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.

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