Sauve C, Azoulay-Dupuis E, Moine P, Darras-Joly C, Rieux V, Carbon C, Bédos J P
Institut National de la Santé et de la Recherche Medicale U 13, Groupe Hospitalier Bichat-Claude Bernard, Paris, France.
Antimicrob Agents Chemother. 1996 Dec;40(12):2829-34. doi: 10.1128/AAC.40.12.2829.
We previously demonstrated the efficacy of ceftriaxone (CRO), at 50 mg/kg of body weight every 12 h, against a highly penicillin-resistant (MIC, 4 micrograms/ml) Streptococcus pneumoniae strain with low-level resistance to CRO (MIC, 0.5 microgram/ml) in a leukopenic-mouse pneumonia model (P. Moine, E. Vallée, E. Azoulay-Dupuis, P. Bourget, J.-P. Bédos, J. Bauchet, and J.-J. Pocidalo, Antimicrob. Agents Chemother. 38:1953-1958, 1994). In the present study, we assessed the activity of CRO versus those of cefotaxime (CTX) and amoxicillin (AMO) against two highly penicillin- and cephalosporin-resistant S. pneumoniae strains (P40422 and P40984) (MICs of 2 and 8 for penicillin, 2 and 4 for AMO, and 4 and 8 for CRO or CTX, respectively). Against both strains, a greater than an 80% cumulative survival rate was observed with CRO at a dose of 100 or 200 mg/kg every 12 h (dose/MIC ratio, 25). With CTX, a high dosage of 400 mg/kg (dose/MIC ratio, 100 or 50) administered every 8 h (TID) was needed to protect 66 and 75% of the animals, respectively, with no statistically significant differences versus CRO. Against the P40422 strain, CRO (100 mg/kg) produced the greatest bactericidal effect, from the 8th to the 24th hour after a single injection (1.8-log-unit reduction over 24 h), and the fastest bacterial pulmonary clearance during treatment; with CTX, only multiple injections at a high dosage, i.e., 400 mg/kg TID, demonstrated a significant bactericidal effect. AMO in a high dosage, 400 mg/kg (dose/MIC ratio, 200) TID, showed good activity only against the P40422 strain. Despite the identical MICs of CTX and CRO, the longer time (3.6 to 4.6 h) that serum CRO concentrations remained above the MICs for the pathogens at a dose of 100 mg/kg resulted in greater efficacy versus CTX against highly penicillin- and cephalosporin-resistant S. pneumoniae strains.
我们之前在白细胞减少小鼠肺炎模型中（P. Moine、E. Vallée、E. Azoulay-Dupuis、P. Bourget、J.-P. Bédos、J. Bauchet和J.-J. Pocidalo，《抗菌药物化疗》38:1953 - 1958，1994年）证明，头孢曲松（CRO）以每12小时50毫克/千克体重的剂量，对一株对青霉素高度耐药（MIC，4微克/毫升）且对CRO低度耐药（MIC，0.5微克/毫升）的肺炎链球菌菌株有效。在本研究中，我们评估了CRO与头孢噻肟（CTX）和阿莫西林（AMO）对两株对青霉素和头孢菌素高度耐药的肺炎链球菌菌株（P40422和P40984）的活性（青霉素的MIC分别为微克/毫升，AMO为2和4微克/毫升，CRO或CTX为4和8微克/毫升）。对于这两株菌株，每12小时给予100或200毫克/千克剂量的CRO时，观察到累积存活率大于80%（剂量/MIC比值，25）。对于CTX，需要每8小时（一日三次）给予400毫克/千克的高剂量（剂量/MIC比值，100或50）才能分别保护66%和75%的动物，与CRO相比无统计学显著差异。对于P40422菌株，CRO（100毫克/千克）在单次注射后第8至24小时产生了最大杀菌效果（24小时内细菌数量减少1.8个对数单位），且在治疗期间细菌从肺部清除最快；对于CTX，只有高剂量多次注射，即400毫克/千克一日三次，才显示出显著杀菌效果。高剂量400毫克/千克（剂量/MIC比值，200）一日三次的AMO仅对P40422菌株显示出良好活性。尽管CTX和CRO的MIC相同，但在100毫克/千克剂量下，血清CRO浓度高于病原体MIC的时间更长（3.6至4.6小时），这使得CRO在对抗对青霉素和头孢菌素高度耐药的肺炎链球菌菌株时比CTX更有效。
