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

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.