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

Abstract

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.

• Authors: A R H van Zanten, M Oudijk, M K E Nohlmans-Paulssen, Y G van der Meer, A R J Girbes, K H Polderman
• Journal: British journal of clinical pharmacology (Br J Clin Pharmacol) Vol. 63 Issue 1 Pg. 100-9 (Jan 2007) ISSN: 0306-5251 [Print] England
• PMID: 16869814 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Bacterial Agents
• Cefotaxime

Topics

• Adult
• Aged
• Anti-Bacterial Agents (administration & dosage, pharmacokinetics, pharmacology)
• Cefotaxime (administration & dosage, pharmacokinetics, pharmacology)
• Disease Susceptibility (etiology)
• Female
• Humans
• Male
• Middle Aged
• Prospective Studies
• Pulmonary Disease, Chronic Obstructive (drug therapy)
• Respiratory Tract Infections (drug therapy)