Evaluation of an alternative extended-infusion piperacillin–tazobactam dosing strategy for the treatment of gram-negative infections

Abstract

Introduction To enhance the probability of pharmacodynamic target attainment, piperacillin-tazobactam can be administered as either a continuous or extended-infusion dosage regimen for the treatment of gram-negative infections. Four hour extended-infusions of piperacillin-tazobactam 3.375 g administered intravenously (IV) every 8 h have been widely studied as an alternative to conventional, intermittent dosage regimens with largely favorable outcomes. Objective To assess the clinical and economic impact of a novel 3-h extended-infusion piperacillin-tazobactam dosing strategy for the treatment of gram-negative infections. Setting 433-bed community hospital in Lexington, KY. Methods Retrospective cohort study before and after the implementation of an alternative dosing protocol using a 3-h infusion of piperacillin-tazobactam 3.375 g IV every 6 h. Main outcome measures The primary outcome was in-hospital mortality. Secondary outcomes include length of stay, ICU length of stay, 30-day all-cause hospital readmissions, total cost per admission, complications, and a composite of in-hospital mortality and readmission within 30 days of discharge. Results Readmission within 30 days of hospital discharge was significantly reduced in the extended-infusion arm (1.2 vs. 13.7 %, P = 0.002). A composite endpoint of death or readmission was lower among patients who received the extended-infusion dosing regimen [ORadj 0.20; 95 % CI (0.07-0.57)]. However this was likely driven by reductions in readmission. Conclusion An alternative regimen of extended-infusion piperacillin-tazobactam resulted in a significant reduction in 30-day all-cause hospital readmission. These results indicate that 3-h infusions of piperacillin-tazobactam 3.375 g IV every 6 h may represent a clinically effective alternative to other commonly used regimens and results in fewer readmissions within 30 days.

Optimal infusion rate in antimicrobial therapy: explosion of evidence in the last five years

“…Compared to the conventional intermittent dosage regimen, prolonged piperacillin/tazobactam infusion resulted in shorter ICU and hospital LOS among adult critically ill patients (ie, saving 0.6 days and 5.6 days, respectively), 29 a significantly lower rate of readmission within 30 days of hospital discharge (1.2% vs 13.7%, P =0.002), 30 and greater PTA in critically ill patients receiving continuous renal replacement therapy or critically ill patients with severe sepsis or septic shock undergoing continuous venovenous hemofiltration. 31 , 32 …”

Comparing Clinical Outcomes of Piperacillin-Tazobactam Administration and Dosage Strategies in Critically Ill Adult Patients: A Systematic Review and Meta-Analysis

“…An additional two studies that met the inclusion criteria were acknowledged through checking references of relevant studies. Twenty-three studies met the described inclusion criteria and were included in the systematic review (13,14,(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)15,33,34,(16)(17)(18)(19)(20)(21)(22). The article selection process is illustrated in Figure.1 and selected studies comparing clinical outcome between CI and II of piperacillin are listed in Table.2.…”

“…Fifteen of the included studies reported length of hospital stay (13,14,31,33,34,36,38,15,16,18,23,24,26,29,30). Pooling of studies showed that patients receiving C/PI had a signi cantly shorter length of hospital stay (2101 patients; Mean Difference -1.27, 95% C.I -2.45-0.08, P = 0.04; Figure 9) The meta-analysis suggests there is a signi cant reduction in the length of hospital stay in patients receiving C/PI compared to those receiving II.…”

Comparing Clinical Outcomes of Piperacillin-Tazobactam Administration and Dosage Strategies in Critically Ill Adult Patients: A Systematic Review and Meta-Analysis

“…Eighteen of the included studies reported patient mortality rates (Table 1) (13,14,(28)(29)(30)(31)(32)(33)(34)36,(15)(16)(17)(18)20,21,24,27). Statistically significantly fewer mortality rates were found among patients receiving C/PI compared with patients receiving conventional II (3100 patients; OR 0.68, 95% C.I 0.55-0.84, P = 0 .0003; Fig.…”

“…Fifteen of the included studies reported length of hospital stay (13,14,31,(33)(34)(35)37,15,16,18,23,24,26,29,30). Pooling of studies showed that patients receiving C/PI had a significantly shorter length of hospital stay (2101 patients; OR -1.27, 95% C.I -2.45-0.08, P = 0.04; Fig.…”