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PK/PD approach to evaluate Meropenem effectiveness in critically ill burn adolescents versus young adults undergoing therapy of septic shock

Pharmacy & Pharmacology International Journal
Thais Vieira de Camargo,1 Elson Mendes Silva Junior,2 Joao Manoel Silva Jr,2 David de Souza Gomez,2 Silvia R C J Santos1


Meropenem is largely prescribed to septic patients with severe infections caused by gram-negative nosocomial pathogens Enterobacteriaceae (fermenters, EB) and NonEnterobacteriaceae (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, Vdss, CLT) 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 x103 cells/mm3, and neutrophils 14/12x103 cells/mm3 . Total isolates of gram-negate of susceptible strains Enterobacteriaceae and Non-Enterobacteriaceae from cultures (blood, alveolar bronchus lavage, wound, bone, urine) and pathogens isolated of intermediate susceptibility were investigated. Clinical cure occurred for all patients by eradicating gramnegative, susceptible, and intermediate susceptibility, considering K. pneumoniae and P. aeruginosa, MIC 4mg/L. The target of 100%f?T>MIC was attained for all patients of both groups despite the meropenem of significant PK changes between them, and the desired outcome was reached. Finally, PK/PD approach based on drug serum monitoring done in real-time is an important tool to assess drug effectiveness in ICU septic burn patients.


septic shock, burn patients, Meropenem 1 g q8h extended infusion, PK/PD approach, adolescents versus young adults