Isla Arantxazu, Canut Andrés, Rodríguez-Gascón Alicia, Planells Paloma, Beltrí-Orta Paola, Salmerón-Escobar José Ignacio, Labora Alicia, Pedraz José Luis
Laboratorio de Farmacia y Tecnología Farmacéutica, Facultad de Farmacia, Universidad del País Vasco, Spain.
Enferm Infecc Microbiol Clin. 2008 Dec;26(10):621-8. doi: 10.1016/s0213-005x(08)75278-9.
The objective of this study was to evaluate the efficacy of the most commonly used antimicrobial treatments in odontogenic infections in children and adolescents on the basis of pharmacokinetic/ pharmacodynamic (PK/PD) criteria.
Unbound drug plasma concentration-time curves were simulated with mean population pharmacokinetic parameters of amoxicillin, co-amoxiclav, cefuroxime axetil, spiramycin, clindamycin, azithromycin, and metronidazole. For drugs showing time-dependent antibacterial killing, the time above MIC90 of the pathogens studied was calculated (T>MIC). For drugs with concentration-dependent bactericidal activity, the area under the concentration-time curve (AUC)/MIC90 ratio was calculated.
Adequate efficacy indexes (T>MIC>40%) against all the microorganisms examined with the exception of Veillonella spp. were obtained with co-amoxiclav (80 mg/kg/day). Clindamycin (40 mg/kg/day) obtained adequate PK/PD indexes except for Lactobacillus, Actinobacillus actinomycetemcomitans, penicillin-resistant Peptostreptococcus, and Eikenella corrodens. High-dose amoxicillin yielded unsatisfactory results against many bacterial species. Azithromycin and metronidazole showed inadequate efficacy indexes against the majority of pathogens studied (AUC/MIC90<25).
When antibiotic therapy is needed for odontogenic infections in children and adolescents, the most active empirical therapeutic choice is co-amoxiclav with high doses of amoxicillin. Clindamycin can be used as an alternative option. These results should be confirmed in clinical trials, in which the PK/PD approach could be useful for the design and assessment of results.
本研究的目的是根据药代动力学/药效学(PK/PD)标准,评估儿童和青少年牙源性感染中最常用的抗菌治疗方法的疗效。
使用阿莫西林、阿莫西林克拉维酸、头孢呋辛酯、螺旋霉素、克林霉素、阿奇霉素和甲硝唑的平均群体药代动力学参数模拟未结合药物的血浆浓度-时间曲线。对于显示时间依赖性抗菌杀灭作用的药物,计算所研究病原体的高于MIC90的时间(T>MIC)。对于具有浓度依赖性杀菌活性的药物,计算浓度-时间曲线下面积(AUC)/MIC90比值。
除韦荣球菌属外,阿莫西林克拉维酸(80mg/kg/天)对所有检测的微生物均获得了足够的疗效指标(T>MIC>40%)。克林霉素(40mg/kg/天)除对乳酸杆菌、伴放线放线杆菌、耐青霉素消化链球菌和啮蚀艾肯菌外,获得了足够的PK/PD指标。高剂量阿莫西林对许多细菌种类产生的结果不尽人意。阿奇霉素和甲硝唑对大多数所研究的病原体显示出不足的疗效指标(AUC/MIC90<25)。
当儿童和青少年牙源性感染需要抗生素治疗时,最有效的经验性治疗选择是高剂量阿莫西林的阿莫西林克拉维酸。克林霉素可作为替代选择。这些结果应在临床试验中得到证实,其中PK/PD方法可能有助于设计和评估结果。