Gómez-Lus M L, García Y, Valero E, Amores R, Fuentes F
Departamento de Microbiología, Facultad de Medicina, Universidad Complutense de Madrid,Avda. de la Complutense s/n, 28040 Madrid.
Rev Esp Quimioter. 2000 Sep;13(3):306-13.
Amoxicillin-clavulanic acid is a first choice treatment for respiratory tract infections caused by Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis. In a previous study we observed its high efficacy against penicillin-susceptible and intermediate-resistant strains of S. pneumoniae. We aimed to study the efficacy of this antibiotic against three strains of S. pneumoniae (susceptible, intermediate and resistant to penicillin) in a mouse model of pneumonia, and to determine the influence of the time of starting treatment and the in vitro postantibiotic effect. We also determined the serum levels of the antimicrobial agent in the mice, and correlated the pharmacodynamic parameters (Cmax/MIC, AUC/MIC and T>MIC) with the survival rate to establish the best predictor of efficacy. MICs with amoxicillin-clavulanic acid were 0. 03 mg/l, 0.25 mg/l and 2 mg/l for the penicillin-susceptible, -intermediate and -resistant strains, respectively. The ED90 were approximately 5 mg/kg for susceptible strains, 25 mg/kg for the intermediate and 50 mg/kg for the resistant strains. We observed a lower survival rate (approximately 55%) when the treatment began 31 h after infection than when it began 5 h (100%) and 19 h (approximately 90-100%) afterwards. Serum levels were dose dependent and the correlation with the pharmacodynamic parameters showed a significant association between survival and the T>MIC (r = 0.946). In vitro postantibiotic effects with 1, 4 and 10 times the MIC were 0.96 to 1.69 h for susceptible strains, 0.38 to 1.23 h for intermediate, and 1.52 to 2. 20 h for resistant strains. These results show the high efficacy of this antibiotic combination against strains with variable susceptibility to penicillin, with this activity being related mainly to the T>MIC of the microorganism. The postantibiotic effect would prolong the effect of the antibiotic in the dosing interval. These parameters and antimicrobial effects are important in terms of the clinical application of this antimicrobial agent.
阿莫西林-克拉维酸是治疗由肺炎链球菌、流感嗜血杆菌和卡他莫拉菌引起的呼吸道感染的首选药物。在之前的一项研究中，我们观察到它对青霉素敏感和中度耐药的肺炎链球菌菌株具有高效性。我们旨在研究这种抗生素在肺炎小鼠模型中对三株肺炎链球菌（对青霉素敏感、中度敏感和耐药）的疗效，并确定开始治疗的时间和体外抗生素后效应的影响。我们还测定了小鼠体内抗菌剂的血清水平，并将药效学参数（Cmax/MIC、AUC/MIC和T>MIC）与存活率相关联，以确定疗效的最佳预测指标。阿莫西林-克拉维酸对青霉素敏感、中度敏感和耐药菌株的MIC分别为0.03mg/l、0.25mg/l和2mg/l。敏感菌株的ED90约为5mg/kg，中度敏感菌株为25mg/kg，耐药菌株为50mg/kg。我们观察到，感染后31小时开始治疗时的存活率（约55%）低于感染后5小时（100%）和19小时（约90-100%）开始治疗时的存活率。血清水平呈剂量依赖性，与药效学参数的相关性表明存活率与T>MIC之间存在显著关联（r = 0.946）。对于敏感菌株，1、4和10倍MIC的体外抗生素后效应为0.96至1.69小时，中度敏感菌株为0.38至1.23小时，耐药菌株为1.52至2.20小时。这些结果表明，这种抗生素组合对青霉素敏感性不同的菌株具有高效性，这种活性主要与微生物的T>MIC有关。抗生素后效应会延长给药间隔期内抗生素的作用。这些参数和抗菌效果对于这种抗菌剂的临床应用很重要。
