慢性阻塞性肺疾病合并呼吸道感染患者中头孢噻肟持续给药与间歇给药的比较：药代动力学/药效学、细菌敏感性及临床疗效
Continuous vs. intermittent cefotaxime administration in patients with chronic obstructive pulmonary disease and respiratory tract infections: pharmacokinetics/pharmacodynamics, bacterial susceptibility and clinical efficacy.
作者信息
van Zanten A R H, Oudijk M, Nohlmans-Paulssen M K E, van der Meer Y G, Girbes A R J, Polderman K H
机构信息
Department of Intensive Care, Gelderse Vallei Hospital, Ede, the Netherlands.
出版信息
Br J Clin Pharmacol. 2007 Jan;63(1):100-9. doi: 10.1111/j.1365-2125.2006.02730.x. Epub 2006 Jul 21.
AIM
To compare the pharmacokinetics/pharmacodynamics, antibiotic resistance and clinical efficacy of continuous (CA) vs. intermittent administration (IA) of cefotaxime in patients with obstructive pulmonary disease and respiratory infections.
METHODS
A randomized controlled prospective nonblinded study was performed in 93 consecutive hospitalized patients requiring antibiotics for acute exacerbations of chronic obstructive pulmonary disease. Forty-seven patients received 2 g of cefotaxime intravenously over 24 h plus a loading dose of 1 g, and 46 patients were given the drug intermittently (1 g three times daily).
RESULTS
Similar pathogens were identified in both groups, being mostly Haemophilus influenzae (51%), Streptococcus pneumoniae (21%) and Moraxella catharralis (18%). Mean minimal inhibitory concentration (MIC) values were also similar before and after treatment in both groups. Clinical cure was achieved in 37/40 (93%) (CA) vs. 40/43 (93%) (IA) of patients (P = 0.93). In microbiologically evaluable patients, criteria such as 70% of treatment time with antibiotic concentrations > or = MIC (CA 100%vs. IA 60% of patients) and/or > or = 5 x MIC (CA 100%vs. IA 55% of patients) were significantly better following continuous administration (P < 0.01). Samples with suboptimal antibiotic concentrations were found in 0% of CA vs. 65% of IA patients (P < 0.01).
CONCLUSIONS
Although clinical cure rates were comparable, continuous cefotaxime administration led to significantly greater proportions of concentrations > MIC and > 5 x MIC compared with intermittent dosing. Continuous administration of cefotaxime at a lower dose [2 g (CA) vs. 3 g (CI)] is equally effective pharmacodynamically and microbiologically, may be more cost-effective and offers at least the same clinical efficacy. Based on these observations, we recommend continuous administration of cefotaxime as the preferred mode of administration.
目的
比较头孢噻肟持续给药（CA）与间歇给药（IA）在慢性阻塞性肺疾病合并呼吸道感染患者中的药代动力学/药效学、抗生素耐药性及临床疗效。
方法
对93例因慢性阻塞性肺疾病急性加重而需使用抗生素的连续住院患者进行了一项随机对照前瞻性非盲研究。47例患者在24小时内静脉输注2g头孢噻肟加1g负荷剂量，46例患者间歇给药（每日3次，每次1g）。
结果
两组鉴定出的病原体相似，主要为流感嗜血杆菌（51%）、肺炎链球菌（21%）和卡他莫拉菌（18%）。两组治疗前后的平均最低抑菌浓度（MIC）值也相似。37/40（93%）（CA组）和40/43（93%）（IA组）的患者实现了临床治愈（P = 0.93）。在微生物学可评估的患者中，连续给药后，诸如抗生素浓度>或= MIC的治疗时间占70%（CA组为100%，IA组为60%的患者）和/或>或= 5×MIC（CA组为100%，IA组为55%的患者）等标准明显更好（P < 0.01）。CA组0%的患者与IA组65%的患者发现抗生素浓度未达最佳（P < 0.01）。
结论
虽然临床治愈率相当，但与间歇给药相比，头孢噻肟持续给药导致浓度> MIC和> 5×MIC的比例显著更高。以较低剂量[2g（CA组）对3g（CI组）]持续给予头孢噻肟在药效学和微生物学上同样有效，可能更具成本效益且具有至少相同的临床疗效。基于这些观察结果，我们推荐将头孢噻肟持续给药作为首选给药方式。
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