Loo Angela S, Neely Michael, Anderson Evan J, Ghossein Cybele, McLaughlin Milena M, Scheetz Marc H
New York-Presbyterian/Weill Cornell Medical Center, New York, New York, USA.
Antimicrob Agents Chemother. 2013 Dec;57(12):5854-9. doi: 10.1128/AAC.00474-13. Epub 2013 Sep 9.
Ceftazidime is a broad-spectrum cephalosporin with high-level activity against a variety of Gram-negative pathogens, including Pseudomonas aeruginosa. Improved outcomes are associated with cumulative percentages of a 24-h period that the drug concentration exceeds the MIC under steady-state pharmacokinetic conditions (%TMIC) of >45 to 70% of the dosing interval. Optimal dosing to achieve a 90% probability of target attainment (PTA) in patients receiving high-flux hemodialysis (HFHD) is unknown. We used existing data from six anephric adults receiving hemodialysis to construct a population model with the Pmetrics package for R. From the final model's joint probability density, we simulated the PTA for various ceftazidime dosing regimens, HFHD schedules, and organism MICs. For HFHD every 48 h and 1 g of ceftazidime given posthemodialysis, the PTA exceeds 90% for all isolates with MICs of ≤8 μg/ml, assuming a goal of 70%TMIC. For 72-h dialysis intervals, postdialysis dosing of 1 g is adequate for achievement of the 70%TMIC goal only for organisms with MICs of ≤4 μg/ml, while 2 g is adequate for organisms with MICs of ≤8 μg/ml. A dose of 500 mg once daily, regardless of HFHD schedule, has a 90% PTA for organisms with MICs of ≤16 μg/ml, while 1 g once daily may achieve 100% PTA even for resistant organisms with a MIC of 32 μg/ml. Therefore, to ensure maximal ceftazidime activity, once-daily dosing of 500 mg to 1 g ceftazidime in patients receiving HFHD may be preferable for critically ill patients when MIC data are unavailable and for more resistant organisms with ceftazidime MICs of 16 to 32 μg/ml.
头孢他啶是一种广谱头孢菌素，对包括铜绿假单胞菌在内的多种革兰氏阴性病原体具有高活性。在稳态药代动力学条件下，药物浓度超过最低抑菌浓度（MIC）的24小时累积百分比（%TMIC）达到给药间隔的45%至70%时，治疗效果会得到改善。在接受高通量血液透析（HFHD）的患者中，实现90%目标达成概率（PTA）的最佳给药方案尚不清楚。我们使用来自6名接受血液透析的无肾成年人的现有数据，通过用于R的Pmetrics软件包构建了一个群体模型。根据最终模型的联合概率密度，我们模拟了各种头孢他啶给药方案、HFHD时间表和微生物MIC的PTA。对于每48小时进行一次HFHD且透析后给予1克头孢他啶的情况，假设目标为70%TMIC，所有MIC≤8μg/ml的分离株的PTA超过90%。对于72小时的透析间隔，透析后给予1克剂量仅对MIC≤4μg/ml的微生物足以实现70%TMIC目标，而对于MIC≤8μg/ml的微生物，2克剂量足够。无论HFHD时间表如何，每日一次500毫克的剂量对于MIC≤16μg/ml的微生物具有90%的PTA，而每日一次1克的剂量甚至对于MIC为32μg/ml的耐药微生物可能实现100%的PTA。因此，为确保头孢他啶的最大活性，对于接受HFHD的患者，当无法获得MIC数据时，对于病情危重的患者以及对于头孢他啶MIC为16至32μg/ml的更耐药微生物，每日一次给予500毫克至1克头孢他啶可能更可取。
