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This randomised prospective non-blinded study compared the pharmacokinetics, pharmacodynamics, antibiotic resistance and clinical efficacy of continuous vs intermittent administration of cefotaxime in 93 patients with chronic obstructive pulmonary disease (COPD) requiring hospitalisation for moderate to severe community acquired exacerbations (GOLD stages 2–4). Forty-seven patients received 2 g of cefotaxime as a continuous infusion over 24 h plus a loading dose of 1 g, while 46 patients received the drug intermittently (1 g three times daily). The mean duration of treatment was 10 days.
The most commonly isolated pathogens were Haemophilus influenzae, Streptococcus pneumoniae and Moraxella catarrhalis. Clinical cure was achieved in 37/40 (93%) with continuous infusion and 40/43 (93%) with intermittent administration (p = 0.93). No patients in the continuous group had antibiotic concentrations lower than minimal inhibitory concentration (MIC) compared with 40% in the intermittent group. Samples with <5 MIC (the optimal bactericidal concentration) were found in no patients on continuous infusion but 65% in the intermittent group. Serum drug concentrations <5 MIC for more than 30% of the treatment time (a feature associated with risk of antibiotic resistance) did not occur in patients in the continuous group compared with 45% in the intermittent group (all p<0.01). The mean MIC values were similar before and after treatment in both groups.
The authors conclude that continuous administration of β lactam antibiotics such as cefotaxime preceded by a loading dose is equally effective compared with intermittent bolus administration and has potentially important pharmacological advantages, may be more cost-effective and could help to decrease staff workload. Long-term effects on antibiotic resistance are yet to be determined. It is worth remarking that these exacerbations included patients with radiological infiltrates, and that intravenous cefotaxime is not first line treatment in uncomplicated exacerbations of COPD.
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