Lunes, 20 Mayo 2019 17:08

GENTAMICIN AND PIPERACILLIN – TAZOBACTAM is there a CHEMICAL INTERACTION?

Escrito por 

 Congreso Internacional 

Noceti, OM; Woillard, JB; Prieto, JB; Medina, JC; Gerona, S . GENTAMICIN AND PIPERACILLIN – TAZOBACTAM is there a CHEMICAL INTERACTION? 17th International Congress of Therapeutic Drug Monitoring & Clinical Toxicology. Foz do Iguassu, Brazil, 22-26 September, 2019.

 

Background: As part of the surgical prophylaxis protocol in liver transplantation 60 minutes of pre-surgical incision, the recipient receive a loading dose of gentamicin of 5mg/Kg diluted in 200 mL of saline solution 0.9% in 30 minutes associated with 4.5 g of piperacillin-tazobactam diluted in 250 mL of glucose solution 5% in short infusion. This is followed by continuous infusion of piperacillin-tazobactam 13.5g over 8h and then 4.5g every 8h for the next 2 days. If bleeding exceeds 1500 mL intra-procedure, a second drip of gentamicin 2mg/kg is administrated. The goal is to prevent surgical site infection due to Coccus Gram+ and Multidrug resistant Gram-negative bacteria t, due to synergistic bactericide effect and extended spectrum, avoiding carbapenems. As it has been postulated that the carboxylate group of the piperacillin is susceptible of nucleophilic attack by the amino group of the glycoside resulting in an inactive amide, with beta-lactam as the limiting substrate of the reaction we wanted to assess this potential interaction in-vivo. Concomitantly use of other antibiotics with gentamicin yield lower target peaks and through concentrations of gentamicin.
Methods: Our sampling strategy was to take peripheral blood samples 30 minutes, 3.5 and 6.5 hours after gentamicin administration was finished. Piperacillin –tazobactam begins once of gentamicin load finishes. Results were modelized by Bayesian estimation in Limoges. Gentamicin determinations were measured by Architect. 14 patients who underwent for liver transplantation in Uruguay during 2018 with this prophylactic regimen were compared with 10 patients of Limoges cardiac surgical services on similar doses of gentamicin.
Results: After Student’s test, significant p values were obtained for AUC, half-life elimination time and creatinine clearance. Gentamicin elimination is by glomerular filtration. In both groups of patients Cmax did not reach theoretical 30-40 mg/L levels. Despite they exhibit similar distribution volume, Cmax and Caverage, their AUCs are quite different, pointing toward a disparity in absorption regardless Vd and Cmax. similarities. None of our patients developed intra-abdominal infections.

Grafico-1

Conclusions: Both groups achieved theoretical target peaks; besides our Cmin remains within the non-toxic levels. AUC, creatinine clearance and half-life elimination of gentamicin could be more reliable parameters to evaluate PK profile during liver transplant procedures.

 

 

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