What is the recommended vancomycin trough level target in pediatric patients?

Vancomycin Trough Level Target in Pediatrics

For pediatric patients with serious infections (bacteremia, endocarditis, osteomyelitis, meningitis, pneumonia, severe skin/soft tissue infections), target trough concentrations of 15-20 mg/L should be considered, though the efficacy and safety of this range requires additional study in children. 1

Infection Severity-Based Targeting

Serious/Invasive Infections

• Target trough: 15-20 mg/L for serious infections including bacteremia, endocarditis, osteomyelitis, meningitis, pneumonia, and necrotizing fasciitis 1
• This higher target mirrors adult recommendations but comes with the caveat that pediatric-specific evidence remains limited 1
• The American Heart Association recommends this range for children beyond the neonatal period with infective endocarditis 1

Mild to Moderate Infections

• Target trough: 10-15 mg/L for less severe infections 1
• This lower range reduces nephrotoxicity risk while maintaining adequate antimicrobial coverage 2

Critical Dosing Considerations

Initial Dosing Strategy

• 15 mg/kg per dose every 6 hours is recommended for children with serious or invasive disease 1
• However, research demonstrates this regimen achieves therapeutic troughs (15-20 mg/L) in only 6.8% of pediatric patients 3
• Higher initial doses of 60-80 mg/kg/day may be necessary to achieve target AUC/MIC ratios >400, particularly in younger children 4, 5, 3

Age-Specific Nuances

• Children <12 years old require approximately 70 mg/kg/day to achieve target AUC/MIC in ~75% of cases 5
• Children ≥12 years old may achieve targets with 60 mg/kg/day 5
• Patients aged 1.0-5.9 years are significantly less likely to achieve therapeutic troughs with standard dosing 3

Monitoring Algorithm

Timing of Trough Measurement

• Obtain trough concentrations at steady state, before the fourth or fifth dose 1
• For dose adjustments, recheck trough before the fourth dose of the new regimen 6

Interpretation and Action

• Trough 15-20 mg/L: Maintain current regimen for serious infections 1
• Trough >20 mg/L: Reduce dose by approximately 12% to lower trough to 16-18 mg/L range, as levels >20 mg/L increase nephrotoxicity risk without additional benefit 6
• Trough <15 mg/L: Increase dose; median dose achieving therapeutic troughs is 80 mg/kg/day 3
• Trough 10-15 mg/L: Acceptable for mild-moderate infections 1, 2

Important Caveats and Pitfalls

The Trough vs. AUC Controversy

• Targeting troughs >15 mg/L may overshoot the target AUC/MIC >400 and expose children to unnecessary nephrotoxicity 4
• Research shows that an AUC/MIC of ~400 corresponds to trough concentrations of only 8-9 mg/L in pediatric patients 5
• Trough levels of 11-15 mg/L achieved target AUC >400 in 95% of children, while troughs of 7-11 mg/L achieved it in only 46% 4
• This suggests that troughs of 10-15 mg/L may be more appropriate than 15-20 mg/L for most pediatric patients to balance efficacy and safety 4

Nephrotoxicity Risk

• Troughs >15 mg/L significantly increase nephrotoxicity risk, especially in critically ill infants receiving other nephrotoxic agents 6
• Monitor serum creatinine closely; nephrotoxicity is defined as consecutive increases ≥0.5 mg/dL or ≥50% from baseline 6

Dosing Interval Considerations

• The every-6-hour interval is essential in pediatric patients; every-8-hour regimens produce inadequate troughs (~9 mg/L) that risk treatment failure and resistance development 6
• Maximum single dose should not exceed 750 mg per some institutional protocols 2

MIC-Dependent Decisions

• For isolates with vancomycin MIC ≥2 μg/mL, switch to alternative agents (daptomycin, linezolid, or ceftaroline) as target AUC/MIC ratios are not achievable 1

Quality Improvement Data

• Implementation of standardized higher-dose protocols (15 mg/kg for mild/moderate, 20 mg/kg for severe infections, both every 6 hours) increased initial therapeutic trough achievement from 6.1% to 20.9% 2
• Time to therapeutic trough decreased from 2.78 to 1.56 days with no increase in toxicity 2
• Traditional 40 mg/kg/day dosing achieved troughs >10 mg/L in only 14% of patients, compared to 49% with 60 mg/kg/day 7