Does vancomycin administered at an empirical dose ensure coverage of pediatric patients against grampositive pathogens?

Abstract

Objective To investigate the vancomycin effectiveness against gram-positive pathogens with the minimum inhibitory concentration of 1mg/L in pediatric patients based on the area under the curve and the minimum inhibitory concentration ratio > 400. Methods A population of 22 pediatric patients (13 boys) admitted to the pediatric intensive care unit with preserved renal function was stratified in two groups (G1 < 7 years and G2 ≥ 7 years). After the fourth dose administered of vancomycin (10 - 15mg/kg every 6 hours) was administered, two blood samples were collected (third and fifth hours), followed by serum measurement by immunoassays to investigate the pharmacokinetics and antimicrobial coverage. Results There was no difference between the groups regarding dose, trough level or area under the curve. Coverage against gram-positive pathogens with a minimum inhibitory concentration of 1mg/L occurred in only 46% of patients in both groups. The pharmacokinetics in both groups were altered relative to the reference values, and the groups differed in regard to increased total body clearance and shortening of the biological half-life, which were more pronounced in younger patients. Conclusion A minimum empirical dose of 60mg/kg per day should be prescribed for pediatric patients in intensive care units with preserved renal function. The use of the ratio between the area under the curve and minimum inhibitory concentration in the evaluation of vancomycin coverage is recommended to achieve the desired outcome, since the pharmacokinetics are altered in these patients, which may impact the effectiveness of the antimicrobial.

Vancomycin area under the curve-guided monitoring in pediatric patients

“…Le et al noted that daily doses of 60 to 70mg/kg were required to achieve the target AUC/MIC in 75% of pediatric patients, and Pires et al recommended a minimum empirical dose of 60mg/kg per day to achieve the desired outcome. ( 17 , 18 )…”

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

“…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.…”

“…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.…”

Combined vancomycin-meropenem therapy in pediatric major burns undergoing therapy of septic shock guided by cultures and pharmacokineticpharmacodynamics approach based on serum levels to combat bacterial resistance

“…15 Considering the previous pharmacokinetic studies of dose adjustment done in pediatric or in adult septic burns, it is well known that its coverage is impacted by differences in pharmacokinetics of vancomycin, due a reduction on biological half-life due to increases on total body clearance age dependently, or even changes that occurs in drug elimination by vasopressors requirements were expected at the earlier stage of septic shock (Figure 1,2). [18][19][20][21][22][23][24][25] Figure 1 Vancomycin PK/PD approach for drug effectiveness after the empirical dose regimen versus individualized therapy in pediatric septic burn patients. patients receiving the same empiric dose regimen (10-15mg/kg q6h, 1hr infusion) recommended for ICU pediatric patients.…”