title: Pharmacokinetic/pharmacodynamic profiling of imipenem in patients admitted to an intensive care unit in India: A nonrandomized, cross-sectional, analytical, open-labeled study.
abstract: OBJECTIVE
  Widespread use of imipenem in intensive care units (ICUs) in India has led to the development of numerous carbapenemase-producing strains of pathogens. The altered pathophysiological state in critically ill patients could lead to subtherapeutic antibiotic levels. Hence, the aim of this study was to investigate the variability in the pharmacokinetic and pharmacodynamic profile of imipenem in critically ill patients admitted to an ICU in India.
  
  
  METHODS
  Plasma concentration of imipenem was determined in critically ill patients using high performance liquid chromatography, at different time points, by grouping them according to their locus of infection. The elimination half-life (t΍) and volume of distribution (Vd) values were also computed. The patients with imipenem trough concentration values below the minimum inhibitory concentration (MIC) and 5 times the MIC for the isolated pathogen were determined.
  
  
  RESULTS
  The difference in the plasma imipenem concentration between the gastrointestinal and the nongastrointestinal groups was significant at 2 h (P = 0.015) following drug dosing; while the difference was significant between the skin/cellulitis and nonskin/cellulitus groups at 2 h (P = 0.008), after drug dosing. The imipenem levels were above the MIC and 5 times the MIC for the isolated organism in 96.67% and 50% of the patients, respectively.
  
  
  CONCLUSIONS
  The pharmacokinetic profile of imipenem does not vary according to the locus of an infection in critically ill patients. Imipenem, 3 g/day intermittent dosing, maintains a plasma concentration which is adequate to treat most infections encountered in patients admitted to an ICU. However, a change in the dosing regimen is suggested for patients infected with organisms having MIC values above 4 mg/L.
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; critically ill patients; imipenem; intensive care unit; pharmacokinetics/pharmacodynamics