Serum monitoring and PK/PD analysis of vancomycin and piperacillin for sepsis control in burn patients

Introduction: Metabolic and hemodynamic changes were reported in critically ill patients including burn patients in sepsis. Then, pharmacokinetics is altered in those patients mainly for hydrophilic antimicrobial agents prescribed for the control of severe bacterial infections; consequently, the therapeutic target wasn't reached based on drug plasma concentrations lower than expected. Antimicrobial therapy recommended in sepsis suspicious is based in a combination of two antimicrobials; vancomycin, a glycopeptides derivative and a beta-lactam agent piperacillin-tazobactam, a beta-lactamase inhibitor. Objective: It was proposed a pharmacokinetic investigation for vancomycin and piperacillin based on drug plasma monitoring followed by drug effectiveness measurements by PK/PD analysis after the empiric dose regimen recommended to normal renal function or renal failure burn patients in sepsis. Methods: 42 adult burn patients of both gender (33M/9F) with deep 2nd and 3rd injuries in septic shock by nosocomial pathogens under intensive care were investigated. A combined antimicrobial therapy at the recommended empirical dose regimen vancomycin-piperacillin was prescribed on the basis of renal function. Characteristics of population of patients investigated, means/SD were: 40.9±17.5 yrs, 70.1±11.5 kg, 33.6±20.7% total burn surface area (TBSA). Normal renal function was registered in 37/42 patients against 5/42 of them with renal failure. Thermal/electrical injuries occur in 39/3, and inhalation injury were in 25 of them. A serial of 2-3 blood samples were obtained from venous catheter into vacuum tubes (sodium EDTA); after centrifugation (2800g) plasma samples were obtained for drug plasma monitoring; both analytes, vancomycin and piperacillin were quantified by high performance liquid chromatography. Pharmacokinetics investigation based on one compartment open model was performed. PK/PD analysis was done to determine antimicrobial effectiveness against nosocomial pathogens isolated. Recommended drug effectiveness index was AUCss 0-24/MIC > 400 for vancomycin and 70%fΔT>MIC for piperacillin. Results: Pharmacokinetics for both antimicrobials investigated showed to be altered in a different extension for vancomycin and piperacillin in burn patients with normal renal function by comparison with reference data reported in healthy adult volunteers. PK/PD analysis indicated that after the initial dose regimen 2g daily for patients with normal renal function, the vancomycin effectiveness occurs only for susceptible pathogens MIC 1mg/L, once drug effectiveness falls to 49% (18/37) against pathogens (MIC 2mg/L). Similarly, piperacillin effectiveness occurs just for susceptible pathogens MIC ≤ 4 mg/L in patients with normal renal function, once only 22/37 (60%) of patients reached the target MIC 16mg/L for Pseudomonas aeruginosa and Enterococcus spp. Conclusion: Vancomycin and piperacillin plasma monitoring indicated that the therapeutic target wasn´t reached with the empiric dose regimen recommended against nosocomial pathogens vancomycin susceptible (MIC>1mg/L) and piperacillin susceptible (MIC >4 mg/L) due to plasma levels lower than expected as a consequence of kinetic disposition altered for both antimicrobials