Rationale and evidence for extended infusion of piperacillin-tazobactam

Purpose. The pharmacodynamics and therapeutic effects of extended-infusion (El) piperacillin-tazobactam therapy are reviewed, with an emphasis on growing evidence of its advantages over traditional infusion schemes. Summary. El beta-lactam therapy is now considered a key aspect of antimicrobial stewardship, and published evidence indicates that iv. infusion of piperacillin-tazobactam over extended periods (e.g., four hours) instead of the traditionally recommended 30 minutes may offer several advantages, including reduced mortality and length of hospital stay and lower treatment cost. A substantial body of evidence from in vitro and animal studies indicates that El enhances the pharmacodynamic profile of piperacillin-tazobactam, particularly by extending the time the free drug level remains above the minimum inhibitory concentration. In one published study comparing the use of El and traditional piperacillin-tazobactam infusion schemes in critically ill patients with Pseudomonas aeruginosa infection, El therapy was associated with significantly improved 14-day mortality and significantly shorter hospital stays; a few other studies have yielded less favorable results. Pharmacoeconomic evaluations indicate that El can offer significant cost benefits. However, evidence of the benefits of El in actual clinical practice remains relatively weak, highlighting the need for large, controlled clinical trials to define its optimal role in patient care. Conclusion. The pharmacodynamic profile of El piperacillin-tazobactam therapy; evidence of its benefits over traditional 30-minute infusions in terms of mortality, duration of hospitalization, clinical and microbiological cure rates, and reduction of fever; and El's lower total treatment cost suggest that El may be the superior mode of administration.