Continuous vs. intermittent cefotaxime administration in patients with chronic obstructive pulmonary disease and respiratory tract infections:: pharmacokinetics/pharmacodynamics, bacterial susceptibility and clinical efficacy

被引:39
作者
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
[1] Gelderse Vallei Hosp, Dept Intens Care, NL-6710 HN Ede, Netherlands
[2] Gelderse Vallei Hosp, Dept Pulmonol, NL-6710 HN Ede, Netherlands
[3] Gelderse Vallei Hosp, Dept Microbiol, NL-6710 HN Ede, Netherlands
[4] Gelderse Vallei Hosp, Dept Pharm, NL-6710 HN Ede, Netherlands
[5] Vrije Univ Amsterdam, Med Ctr, Dept Intens Care, NL-1081 HV Amsterdam, Netherlands
关键词
beta-lactam antibiotics; cefotaxime; continuous infusion; COPD; pharmacodynamics; pharmacokinetics;
D O I
10.1111/j.1365-2125.2006.02730.x
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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 >= MIC (CA 100% vs. IA 60% of patients) and/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.
引用
收藏
页码:100 / 109
页数:10
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