title: Vancomycin Therapeutic Targets and Nephrotoxicity in Critically Ill Children With Cancer.
abstract: To obtain pharmacokinetic and pharmacodynamic data for vancomycin in a cohort of critically ill pediatric oncology patients, we analyzed 256 measurements of vancomycin concentrations in 94 patients. Variables were tested as possible risk factors for vancomycin-related nephrotoxicity or death for 28 days. We found the following: mean vancomycin trough serum concentration, 15.6 ± 12.4 μg/mL; mean vancomycin clearance, 0.16 ± 0.098 L/h/kg; and mean vancomycin distribution volume, 1.04 ± 0.11 L/kg. Only 13.6% of serum trough level measurements were between 15 and 20 μg/mL. The trough levels showed a strong correlation with the AUC (area under the curve of serum concentrations vs. time over 24 h to the minimum inhibitory concentration ratio), with a 94% positive predictive value for AUC/MIC ≥ 400, but only for MIC=1. The doses that are currently used (60 mg/kg/d) attained the therapeutic target (AUC/MIC ≥ 400) in only 56% of measurements, considering MIC=1. A serum trough level of ≥ 20 μg/mL was an independent risk for nephrotoxicity (P = 0.0008; odds ratio = 17.83). Vancomycin-related nephrotoxicity was a predictor of death for up to 28 days (P = 0.003, odds ratio = 7.68). Currently administered doses of vancomycin do not reach the therapeutic target for critical cancer patients, particularly if staphylococci isolates have a MIC>1.
authors.affiliation: From the Pediatric Oncology Institute (IOP/GRAACC)/ Sao Paulo Federal University, Sao Paulo, Brazil.
authors.forename: Glaucia T F
authors.initials: GT
authors.lastname: Seixas
authors.forename: Orlei R
authors.initials: OR
authors.lastname: Araujo
authors.forename: Dafne C B
authors.initials: DC
authors.lastname: Silva
authors.forename: Rodrigo G
authors.initials: RG
authors.lastname: Arduini
authors.forename: Antonio S
authors.initials: AS
authors.lastname: Petrilli
mesh_terms: D000293:Adolescent; D000900:Anti-Bacterial Agents / Q000009:adverse effects* / Q000493:pharmacokinetics*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D019540:Area Under Curve; D002648:Child; D002675:Child, Preschool; D016638:Critical Illness; D005260:Female; D006801:Humans; D007223:Infant; D007668:Kidney / Q000187:drug effects*; D008297:Male; D008826:Microbial Sensitivity Tests; D009369:Neoplasms / Q000188:drug therapy; D013203:Staphylococcal Infections / Q000188:drug therapy; D014640:Vancomycin / Q000009:adverse effects* / Q000493:pharmacokinetics*
chemical_list: D000900:Anti-Bacterial Agents; D014640:Vancomycin