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.
Meropenem is largely prescribed to septic patients with severe infections caused by gram-negative nosocomial pathogens Enterobacteriaceae (fermenters, EB) and Non-Enterobacteriaceae (non-fermenters, NEB). Pharmacokinetics (PK) changes reported previously in burns can affect the desired outcome by physiopathology alterations during the systemic inflammatory response syndrome. The study aimed to investigate if the target is attained in septic burn patients' adolescents versus young adults receiving the same recommended meropenem dose regimen by extended infusion. Ethical approval register CAAE 07525118.3.0000.0068 was obtained; no conflicts of interest to declare were obtained from all authors. Septic burn patients (16M/4F) were included after the fire or electrical injury (16/4), respectively. Patients have preserved renal function at admission in the Intensive Care Unit (ICU), and during the meropenem pharmacokinetic-pharmacodynamics (PK/PD) approach done by therapeutic drug monitoring (TDM) patient's bedside number beef patients (N) was estimated according to Power & Sample Size Calculation, software v. 3.0.43; estimated power of 80% was considered. Twenty patients were allocated into two groups: G1: 10 adolescents, and G2: 10 young adults. Characteristics of burn patient's admission were: G1/G2 16/25 yrs, 60/70 kg ideal body weight, 40/34% total burn surface area, simplified acute physiologic score III (SAPS3) 53/56 and 23/7% for the risk of death, medians. Inhalation injury occurred in 13/20 G1:G2 patients (5:8, proportion); mechanical ventilation in 18/20 (9:9; G1:G2), and vasoactive drugs were required in 15/20 patients (7:8; G1:G2) undergoing therapy of septic shock with meropenem 1 g q8h by extended 3hr infusion. Cultures were before the antimicrobial therapy started Blood was sampled and only two samples were required (2 ml/each) at the steady-state level for drug serum measurements done by liquid chromatography. Pharmacokinetics (PK) data parameters (Kel t (1/2)β , Vd ss , CL T ) obtained from burn patients were compared with the results reported in adults healthy volunteers. Target of 100% f∆T>MIC recommended was considered to evaluate patient's meropenem effectiveness; biomarkers were monitored since patient's admission and during the clinical course of septic shock During the earlier period of the septic shock, important changes occurred in the pharmacokinetics for both groups of burn patients compared with reference data considered for healthy volunteers. Additionality a significant difference between groups (G1/G2) related to the o volume of distribution (23/42 L, p=0.0310), and biological half-life (2.7/3.5 h, p=0.0035) were obtained. Blood was sampled simultaneously for meropenem serum measurements and biomarkers. Data expressed by medians were C-reactive protein 140/185 mg/L G1/G2, white blood cells 17/14 x10 3 cells/mm 3, and neutrophils 14/12x10 3 cells/mm 3 . Total isolates of gram-negate of susceptible strains Enterobacteriaceae and Non-Enterobacteriaceae from cultures (blood, alveolar bronch...
Meropenem is largely prescribed to septic patients with severe infections caused by gramnegative nosocomial pathogens Enterobacteriaceae (fermenters -EB) and Non-Enterobacteriaceae (non-fermenters -NEB). Pharmacokinetics (PK) changes reported previously in burns could impact the desired outcome by physiopathology alterations during the systemic inflammatory response syndrome. The aim of the study was to investigate if the target is attained in septic burn patients' adolescents versus young adults receiving the same recommended meropenem dose regimen by extended infusion. Ethical approval register CAAE 07525118.3.0000.0068 was obtained; no conflicts of interest to declare were obtained from all authors. Burn patients (16M/4F) were included after the accident by fire or electricity (16/4). At admission and meropenem TDM, patients presented preserved renal function. Patients included were stratified in groups: G1: 10 adolescents, and G2: 10 young adults. Characteristics of patient's admission were: G1/G2 16/25 yrs, 60/70 kg ideal body weight, 40/34% total burn surface area, SAPS3 53/56 and 23/7% for the risk of death, medians. Inhalation injury occurred in 13/20 patients (5G1: 8G2, proportion); mechanical ventilation in 18/20 (9G1: 9G2), and vasopressors were required in 15/20 patients (7G1: 8G2) undergoing therapy of septic shock with meropenem 1 g q8h by extended 3hr infusion. Cultures were collected prior to the antimicrobial therapy starts. Only two blood samples were collected (1.5 ml/each) at the steady state level for drug serum measurements done by liquid chromatography. Pharmacokinetics (PK) parameters (t(1/2)β, Vd ss , CLT) from burn patients were compared with the results reported in healthy volunteers. A new target of 100% f∆T>MIC was considered to evaluate patient's meropenem effectiveness; biomarkers were monitored since patient's admission and during the clinical course of septic shock. At the earlier period of the septic shock, it was demonstrated profound changes that occurred on the pharmacokinetics for both groups of burn patients by comparison with reference data from healthy volunteers. Additionally, significant difference between groups (G1/G2) related to volume of distribution (23/42 L, p=0.0310), and biological half-life (2.7/3.5 h, p=0.0035) was obtained. At the same period, blood was sampling for meropenem serum measurements; biomarkers monitored were expressed by medians: CRP140/185 mg/L G1/G2, WBC 17/14 X 103 cells/mm3 and neutrophiles 14/12 X 103 cells/mm3. Total isolates of Gram-negative strains from cultures of blood, alveolar bronchus lavage, and urine were investigated; susceptible Enterobacteriaceae and non-Enterobacteriaceae, and strains of intermediate susceptibility were isolated. Clinical cure occurred for all patients by eradication of gram-negative strains up to MIC 4mg/L, considering K. pneumoniae and P. aeruginosa, MIC 4 mg/L. Target of 100% f∆T>MIC was attained for all patients of both groups, in spite of meropenem PK significant changes between them, and desired outcome wa...
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