Vancomycin and meropenem serum monitoring for target attainment by PK/PD approach as an effective tool in the battle against nosocomial pathogens in septic pediatric burn patients

Abstract

Introduction:Optimizing antimicrobial prescription for severe infections is a challenge in Intensive Care Units for critically ill patients to improve clinical outcome. Aim of the study was to evaluate drug effectiveness in septic pediatric burn patients undergoing combined therapy with vancomycin and meropenem.Methods: Pediatric septic burn patients receiving vancomycin and meropenem combined therapy were included (7F/10M). Characteristics of patient's population, expressed by minimum/maximum values were: 3.1/11.2 yrs; 12/44 kg; 11/75% TBSA; SCr: 0.15/0.47 mg/dL; 10/36 days in ICU, 21/45 days hospitalization for 15 patients. Drug serum measurements were done by liquid chromatography. Pharmacokinetic changes were investigated. Pharmacokinetic-pharmacodynamics (PK/PD) target recommended for vancomycin is AUC ss 0-24 /MIC>400; while the PK/PD meropenem target considered is 100%f∆T>MIC.Results: Target attainment (PTA) MIC 1 mg/L gram-positive strains was reached in 48% with vancomycin Set 1 empiric dose 40-60mg/kg daily 1hr-intermittent infusion (10-15mg/kg q6h); then, optimization of drug therapy was done Set 2 by dose adjustment patient bedside up to 102 mg/kg/day with cure for all patients. Meropenem effectiveness was reached against gram-negative susceptible strains up to MIC 2 mg/L and coverage was extended up to MIC 4 mg/L against strains of intermediate susceptibility due to the extended 3hrs-infusion. Then, meropenem coverage was guaranteed for all patients up to MIC 4 mg/L by recommended dose for ICU pediatric septic patients (40mg/kg q8h) after the extended infusion, to avoid mutant's selection of Klebsiella pneumoniae or Pseudomonas aeruginosa, intermediate susceptibility. Conclusion:A combined therapy with vancomycin -meropenem improves the effectiveness against infections in burn pediatric patients. Vancomycin dose adjustments must be done in real time by PK/PD approach based on serum levels permitting an earlier intervention of ICU Medical Team to reach the desired clinical outcome against nosocomial infections in septic pediatric burn patients and contributes also to avoid the bacterial resistance.

Antimicrobial therapy in severe septic ICU major burn patients to combat bacterial resistance by pharmacokinetic-pharmacodymamics of vancomycin, meropenem, and piperacillin, cultures, and inflammatory biomarkers

“…Antibiotics serum measurements were done by liquid chromatography/ ultraviolet detection (LC-UV, Shimadzu series10, with automatized serum samples extracts injection) of our laboratory at the Clinical Pharmacokinetics Center, as detailed previously. 17,18,20,25,27,28 It is important to highlight that antimicrobial agents were prescribed, and cultures were collected before the therapy with antibiotics start.…”

“…Additionally, PK changes that occurs in pediatric septic patients age dependently affecting vancomycin coverage, even without vasopressor agents. [15][16][17][18][19][20][21] It was demonstrated in table 2, of study that the therapeutic target for vancomycin was achieved at MIC 0.5 mg/L, strains for all patients (27/27) by the vancomycin serum monitoring (TDM-1) with eradication of Gram-positive strains isolated. However, the dose was reduced to 1g every 24 hours in 15/27 patients due to renal failure in TDM-2.…”

“…It is important to highlight that during the septic shock, meropenem plasma clearance is reduced by 50% because of decreases that occurs in drug renal tubular secretion. 17,20,21,[28][29][30][31]…”

“…During combined therapy, the period to death in the ICU for nonsurvivors occurred in 17 (13)(14)(15)(16)(17)(18)(19)(20)(21)11/26 days, table 1. On the other hand, discharge from the ICU occurred in 31(16-55) 8/58 days, and the length of stay of survivors in the hospital was 38 (31-64) 15/113 days.…”