Background and importance Although there is consensus for beta-lactam administration for extended infusions in critical care units, the use of this strategy in emergency departments remains unclear.
Aim and objectives To evaluate the probability of achieving an adequate pharmacokinetic/pharmacodynamic ratio for different dosages of piperacillin/tazobactam in septic patients attending an emergency department.
Material and methods A simulation study was carried out based on gram negative bacterial strains causing bacteraemia in septic patients treated in an emergency department (July 2018–December 2019). Two doses were evaluated, 4/0.5 g every 6 hours or 8 hours given as 0.5 hour or 3 hour infusion, in three different renal clearance rates (<30, 70 and 120 mL/min). Pharmacokinetic parameters were obtained from the literature. Minimum inhibitory concentration (MIC) values to piperacillin/tazobactam were obtained from Spanish records (trial database, TEST). Time above MIC was obtained according to the following equation: fT >MIC=[(t2−tinf)−t1] × (100/τ), where t1 was the time at which the free serum concentration reached the MIC, t2 the post-infusion time at which the free serum concentration equalled the MIC in the elimination phase and τ the dosing interval. A 1000 subject Monte Carlo simulation was performed using Microsoft Excel per dosing and rate of renal function.
Results Sixty patients with gram negative bacteraemia were included. The predominant species were Escherichia coli (34, 56.7%), Klebsiella pneumoniae (14, 23.3%) and Pseudomonas aeruginosa (6, 10%). The probability of target attainment (PTA) fT >100% MIC for piperacillin 4 g/8 hour dose was 60.3% and 81.8% for the 0.5 hour and 3 hour infusions for a ClCr >120 mL/min and 75.1% and 94.3% for a ClCr=70 mL/min. For the 4 g/6 hour dose, the PTA fT >100% MIC was >90% for both infusions at 0.5 and 3 hours. For tazobactam, the PTA fT >70% MIC for a ClCr=70 mL/min for the doses 0.5 g/8 hours and 0.5 g/6 hours were 56% and 89%, increasing in the extended infusion of 3 hours (87% and 98%). For a ClCr >120 mL/min, this probability was significantly reduced, being <50% for the dose 0.5 g/8 hours in a 0.5 hour infusion.
Conclusion and relevance The pharmacokinetic/pharmacodynamic objective of fT >100% MIC for piperacillin/tazobactam required a dose of 4/0.5 g/6 hours or extended infusion, especially in patients with high renal clearance and in strains with high levels of expression of beta-lactamases.
References and/or acknowledgements No conflict of interest.
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