Premium
Continuous vs. intermittent cefotaxime administration in patients with chronic obstructive pulmonary disease and respiratory tract infections: pharmacokinetics/pharmacodynamics, bacterial susceptibility and clinical efficacy
Author(s) -
Van Zanten A. R. H.,
Oudijk M.,
NohlmansPaulssen M. K. E.,
Van Der Meer Y. G.,
Girbes A. R. J.,
Polderman K. H.
Publication year - 2007
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/j.1365-2125.2006.02730.x
Subject(s) - cefotaxime , medicine , pharmacokinetics , streptococcus pneumoniae , pharmacodynamics , antibiotics , respiratory tract infections , gastroenterology , minimum inhibitory concentration , haemophilus influenzae , dosing , pharmacology , respiratory system , microbiology and biotechnology , biology
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 × 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 × 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.