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.Aim: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.Materials and 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.Conclusion: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.