Introdução: O meropenem é um carbapenêmico largamente prescrito aos pacientes sépticos em terapia intensiva com infecções graves causadas por patógenos hospitalares Gram-negativos Enterobacteriaceae (EB) e Non Enterobacteriaceae (NEB) CIM>2 mg/L. As alterações fisiopatológicas que ocorrem nestes pacientes pela síndrome da resposta inflamatória sistêmica decorrente do choque séptico podem causar profundas modificações na farmacocinética impactando o desfecho clínico desejado. Racional do estudo: O objetivo deste estudo foi investigar se o alvo terapêutico foi atingido na fase precoce do choque séptico nos pacientes grandes queimados pela comparação de adolescentes aos adultos jovens em terapia intensiva recebendo o meropenem no regime empírico recomendado. Casuística e Métodos: A aprovação ética foi obtida sob registro CAAE 07525118.3.0000.0068. Incluíram-se 14 pacientes grandes queimados 11M/3F com função renal preservada, após acidente com fogo ou alta voltagem (11/3). Os pacientes incluídos foram distribuídos em dois grupos: G1-Adolescentes, G2-Jovens adultos, sendo que as características dos pacientes, G1/G2 foram 16/24 anos, 60/70 kg, 42/35 % superfície corpórea total queimada, medianas. A lesão inalatória ocorreu em 9/14; a ventilação mecânica e o uso de vasopressor foram requeridos em 13/14 pacientes em choque séptico recebendo meropenem 1g q8h através de infusão estendida de 3 horas.Palavras-chave: Efetividade do meropenem, Terapia do choque séptico, Abordagem PK/PD, Farmacocinética, grandes queimados Adolescentes versus jovens adultos.
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.
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