title: Variability in plasma concentration of cefotaxime in critically ill patients in an Intensive Care Unit of India and its pharmacodynamic outcome: A nonrandomized, prospective, open-label, analytical study.
abstract: BACKGROUND
  Cefotaxime is a widely utilized cephalosporin in most intensive care units of India. However, no data are available about its pharmacokinetic/pharmacodynamic variability in critically ill patients of the Indian population.
  
  
  OBJECTIVE
  To investigate the variability in the plasma concentration and pharmacodynamic profile of intermittent dosing of cefotaxime in critically ill patients, according to their locus of infection and causative organism.
  
  
  METHODS
  Cefotaxime levels were determined using high-performance liquid chromatography by grouping patients according to their locus of infection as hepatobiliary, renal, pulmonary, and others. Patients with cefotaxime concentration below the minimum inhibitory concentration (MIC) and 5 times below the MIC for the isolated organism were determined.
  
  
  RESULTS
  The difference in the plasma cefotaxime concentration between the hepatobiliary and the nonhepatobiliary groups was significant at 1 h (P = 0.02) following drug dosing, while the difference was significant between the renal and nonrenal group at 1 h (P = 0.001), 4 h (P = 0.009), and 8 h (P = 0.02) after drug dosing. The pulmonary group showed significantly (P < 0.05) lower plasma cefotaxime levels than the nonpulmonary group at all-time points. The cefotaxime levels were below the MIC and below 5 times the MIC for the isolated organism in 16.67% and 43.33% of the patients, respectively.
  
  
  CONCLUSIONS
  The concentration of cefotaxime differs according to the locus of an infection in critically ill patients. Use of another class of antibiotic or shifting to continuous dosing of cefotaxime, for organisms having MIC values above 1 mg/L, is advisable due to the fear of resistance.
authors.affiliation: Department of Pharmacology, Vardhman Mahavir Medical College and Safdarjung Hospital, New Delhi, India.
authors.forename: B
authors.initials: B
authors.lastname: Abhilash
authors.affiliation: Department of Pharmacology, Vardhman Mahavir Medical College and Safdarjung Hospital, New Delhi, India.
authors.forename: Chakra Dhar
authors.initials: CD
authors.lastname: Tripathi
authors.affiliation: Department of Anaesthesia, Vardhman Mahavir Medical College and Safdarjung Hospital, New Delhi, India.
authors.forename: Anoop Raj
authors.initials: AR
authors.lastname: Gogia
authors.affiliation: Department of Pharmacology, Vardhman Mahavir Medical College and Safdarjung Hospital, New Delhi, India.
authors.forename: Girish Gulab
authors.initials: GG
authors.lastname: Meshram
authors.affiliation: Department of Pharmacology, Vardhman Mahavir Medical College and Safdarjung Hospital, New Delhi, India.
authors.forename: Manu
authors.initials: M
authors.lastname: Kumar
authors.affiliation: Department of Pharmacology, Vardhman Mahavir Medical College and Safdarjung Hospital, New Delhi, India.
authors.forename: B
authors.initials: B
authors.lastname: Suraj
keywords: Antibiotic resistance; intermittent dosing; locus of infection; minimum inhibitory concentration; pharmacokinetics