van Zanten Arthur R H, Polderman Kees H, van Geijlswijk Ingeborg M, van der Meer Gert Y G, Schouten Marinus A, Girbes Armand R J
Department of Intensive Care, Gelderse Vallei Hospital, 6710 HN Ede, The Netherlands.
J Crit Care. 2008 Sep;23(3):422-30. doi: 10.1016/j.jcrc.2007.11.011. Epub 2008 Apr 18.
Optimal dosing of antibiotics is important for efficacy and avoidance of resistance. Fluoroquinolones are frequently used to treat severe infections in critically ill patients. We studied ciprofloxacin pharmacokinetics after administration of 400 mg twice a day (bid) intravenously (IV).
Serum concentrations were measured in 32 intensive care unit patients (age, 68.7 +/- 17.4 years; Sepsis-related Organ Failure Assessment (SOFA) scores, 7.3 +/- 3.4). Blood samples were drawn at 7 time points after ciprofloxacin infusion. We evaluated whether areas under the curve (AUCs) exceeded minimal inhibitory concentration (MIC) values of 0.125, 0.25, 0.5, 1.0, and 2.0 mg/L by 125 times and peak concentrations (C(max)) 10 x MIC (C(max)/MIC >10).
The AUC/MIC more than 125 was achieved in 100% for MIC 0.125. For MIC values 0.25, 0.5, 1.0, and 2.0, results were 84%, 31%, 3%, and 0%, respectively (P < .01). The C(max)/MIC more than 10 for MIC values of 0.125, 0.25, 0.5, 1.0, and 2.0 was realized in 100%, 97%, 69%, 25%, and 0%, respectively (P < .01). Female sex, SOFA(pulmonary) points, and SOFA(renal) points predicted higher AUC. Cumulative SOFA scores were most predictive of high AUCs.
Ciprofloxacin 400 mg bid IV leads to inadequate AUC/MIC and C(max)/MIC ratios in many cases. Effective killing concentrations were only achieved in pathogens with MIC less than 0.25. As bacteria in intensive care unit patients often exceed this threshold, we recommend to use higher doses of ciprofloxacin (1200 mg daily) to ensure optimal bacterial killing and avoid antibiotic resistance.
抗生素的最佳剂量对于疗效和避免耐药性至关重要。氟喹诺酮类药物常用于治疗重症患者的严重感染。我们研究了每天两次静脉注射（IV）400毫克环丙沙星后的药代动力学。
对32名重症监护病房患者（年龄68.7±17.4岁；脓毒症相关器官功能衰竭评估（SOFA）评分7.3±3.4）进行血清浓度测定。在环丙沙星输注后的7个时间点采集血样。我们评估曲线下面积（AUC）是否超过最低抑菌浓度（MIC）值（0.125、0.25、0.5、1.0和2.0毫克/升）的125倍以及峰值浓度（C(max)）是否超过10×MIC（C(max)/MIC>10）。
对于MIC值0.125，AUC/MIC超过125的比例达到100%。对于MIC值0.25、0.5、1.0和2.0，结果分别为84%、31%、3%和0%（P<.01）。对于MIC值0.125、0.25、0.5、1.0和2.0，C(max)/MIC超过10的比例分别为100%、97%、69%、25%和0%（P<.01）。女性、SOFA（肺部）评分和SOFA（肾脏）评分预示着更高的AUC。累积SOFA评分对高AUC的预测性最强。
每天两次静脉注射环丙沙星400毫克在许多情况下会导致AUC/MIC和C(max)/MIC比值不足。仅在MIC小于0.25的病原体中能达到有效的杀菌浓度。由于重症监护病房患者体内的细菌常常超过这个阈值，我们建议使用更高剂量的环丙沙星（每日1200毫克）以确保最佳的细菌杀灭效果并避免抗生素耐药性。
