Soriano F, Ponte C, Santamaría M, Jimenez-Arriero M
Departamento de Microbiología Clínica, Fundación Jimenez Díaz, Universidad Autónoma, Madrid, Spain.
J Antimicrob Chemother. 1990 Apr;25(4):621-7. doi: 10.1093/jac/25.4.621.
The minimum dosage of antibiotics that reduced mortality in bacteraemic rats inoculated with two different Escherichia coli isolates was determined in an attempt to study the therapeutic importance of the inoculum effect. Low mortality rates (0-5%) at 48 h were obtained when antibiotics with minimal or no inoculum effect (ampicillin, cefuroxime, cefoxitin and gentamicin) were administered to yield serum levels 5 to 14 times the MIC, while antibiotics with a pronounced inoculum effect (piperacillin, cefotaxime and aztreonam) had to be administered to yield serum levels 57 to more than 1000 times the MIC determined with a standard (low) inoculum. All of the antibiotics with inoculum effect studied here are administered empirically in clinical practice at a higher dose than the microbiological and pharmacokinetic data would indicate (in order to reach peak serum concentrations exceeding the MICs of the pathogens by 4-10 times). Our experiment suggests that such high and empirical doses of antibiotics with inoculum effect may be justified.
为研究接种量效应的治疗重要性，测定了用两种不同大肠杆菌分离株接种的菌血症大鼠中降低死亡率的抗生素最低剂量。当给予无接种量效应或接种量效应极小的抗生素（氨苄西林、头孢呋辛、头孢西丁和庆大霉素）使血清水平达到最低抑菌浓度（MIC）的5至14倍时，48小时的死亡率较低（0 - 5%）；而具有显著接种量效应的抗生素（哌拉西林、头孢噻肟和氨曲南）则必须给予使血清水平达到用标准（低）接种量测定的MIC的57至1000倍以上。本文研究的所有具有接种量效应的抗生素在临床实践中经验性给药时的剂量均高于微生物学和药代动力学数据所显示的剂量（以便使血清峰值浓度超过病原体MIC的4至10倍）。我们的实验表明，这种针对具有接种量效应的抗生素的高剂量经验性用药可能是合理的。
