title: Continuous vs. intermittent cefotaxime administration in patients with chronic obstructive pulmonary disease and respiratory tract infections: pharmacokinetics/pharmacodynamics, bacterial susceptibility and clinical efficacy.
abstract: OBJECTIVE
  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.affiliation: Department of Intensive Care, Gelderse Vallei Hospital, Ede, the Netherlands. zantena@zgv.nl
authors.forename: A R H
authors.initials: AR
authors.lastname: van Zanten
authors.forename: M
authors.initials: M
authors.lastname: Oudijk
authors.forename: M K E
authors.initials: MK
authors.lastname: Nohlmans-Paulssen
authors.forename: Y G
authors.initials: YG
authors.lastname: van der Meer
authors.forename: A R J
authors.initials: AR
authors.lastname: Girbes
authors.forename: K H
authors.initials: KH
authors.lastname: Polderman
mesh_terms: D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000494:pharmacology; D002439:Cefotaxime / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D004198:Disease Susceptibility / Q000209:etiology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy*; D012141:Respiratory Tract Infections / Q000188:drug therapy*
chemical_list: D000900:Anti-Bacterial Agents; D002439:Cefotaxime