Use of pharmacodynamic endpoints for the evaluation of levofloxacin for the treatment of acute maxillary sinusitis
Use of pharmacodynamic endpoints for the evaluation of levofloxacin for the treatment of acute maxillary sinusitis
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DOI：
10.1016/j.diagmicrobio.2008.01.010
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发表时间：
2008-05-01
影响因子：
2.9
通讯作者：
Drusano, George L.
中科院分区：
文献类型：
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作者：
Ambrose, Paul G.;Anon, Jack B.;Drusano, George L.
鼻窦炎仍然是美国抗生素处方最常见的原因之一，每年的医疗费用接近 40 亿美元。我们利用连续鼻窦抽吸取样（SSAS）技术获取每日标本，以评估急性上颌窦炎患者的药物作用时程。 18 名经放射学证实患有急性上颌窦炎的患者被纳入一项研究，使用 SSAS 评估左氧氟沙星暴露与抗菌效果时程之间的关系。在治疗期间每天进行 SSAS 以进行细菌学评估。获得了六种稳态左氧氟沙星浓度。使用 S-ADAPT 1.53 中实施的蒙特卡罗参数期望最大化算法对左氧氟沙星血浆和鼻窦抽吸物浓度进行建模。评估的终点包括症状和体征消退的时间以及鼻窦绝育的时间。在 18 名入组患者中，15 名可进行临床评估。从这些微生物中分离出 1 株肺炎链球菌、3 株流感嗜血杆菌、1 株卡他莫拉菌、1 株棒状杆菌和 1 株凝固酶阴性葡萄球菌，后 2 种微生物可能是污染物。对于病原体，左氧氟沙星 MIC 值范围为 0.03 至 2 mg/L。治疗第 4 天时所有病原体均被根除。鼻窦绝育（仅针对病原体）的中位时间和平均时间分别为 1 天和 1.4 天。每种体征和症状消退的中位时间为 1.5 至 12-19 天，其中 83% 的体征和症状在治疗结束（第 5 天）时得到缓解。浓度-时间曲线下的平均血浆面积 (AUC) (mg(.)h/L) 为 100.1（n = 14，%CV = 27）。分离病原体的血浆 AUC/MIC 比率范围为 33.9 至 1696。在这项 SSAS 试点研究中，左氧氟沙星迅速根除上颌窦中分离的病原体。由爱思唯尔公司出版
Sinusitis remains 1 of the most common reasons for antimicrobial prescriptions in the United States, with health care costs approaching $4 billion annually. We utilized the serial sinus aspirate sampling (SSAS) technique to obtain daily specimens to evaluate the time course of drug effect in patients with acute maxillary sinusitis. Eighteen patients with a radiologically confirmed acute maxillary sinusitis were enrolled into a study evaluating the relationship between levofloxacin exposure and the time course of antimicrobial effect using SSAS. SSAS was performed daily during therapy for bacteriologic evaluation. Six steady-state levofloxacin concentrations were obtained. Levofloxacin plasma and sinus aspirate concentrations were modeled using Monte Carlo Parametric Expectation Maximization algorithm implemented in S-ADAPT 1.53. Endpoints evaluated included time to resolution of signs and symptoms and time to sinus sterilization. Among the 18 enrolled patients, 15 were clinically evaluable. From these, 1 Streptococcus pneumoniae, 3 Haemophilus influenzae, 1 Moraxella catarrhalis, 1 Corynebacterium spp., and I coagulase-negative Staphylococcus organisms were isolated, with the latter 2 organisms being likely contaminants. For the pathogens, levofloxacin MIC values ranged from 0.03 to 2 mg/L. All pathogens were eradicated by the 4th day of therapy. The median and mean time to sinus sterilization (pathogens only) was 1 and 1.4 days, respectively. The median time to resolution of each sign and symptom ranged from 1.5 to 12-19 days, with the 83% of total signs and symptoms resolved by the end of therapy (day 5). The mean plasma area under the concentration-time curve (AUC) (mg(.)h/L) was 100.1 (n = 14, %CV = 27). Plasma AUC/MIC ratios ranged from 33.9 to 1696 for isolated pathogens. In this pilot SSAS study, levofloxacin rapidly eradicated isolated pathogens from the maxillary sinus. Published by Elsevier Inc.