Extended Infusion Zosyn

Background / rationale:

For penicillins such as piperacillin/tazobactam the target for optimal bactericidal effects requires 50% fT>MIC.  Numerous recent studies have shown that the standard 3.375 gm Q 6 hr (0.5 hr infusion) regimen is actually inadequate at attaining this pharmacodynamic target for the full range of MIC’s that are deemed susceptible by current breakpoints.  Studies have demonstrated that a dose of 3.375 gm Q 8 hr (4 hr infusion) would better achieve the targeted T>MIC parameter as compared to the usual standard intermittent infusion which would result in greater bactericidal activity.  For the treatment of Pseudomonas aeruginosa, the extended infusion regimen has demonstrated in the literature a significantly lower 14 day mortality and decreased length of stay than the standard regimen.  In addition, the extended infusion regimen would result in cost savings due to one less dose being required per day.

Procedure:

Pharmacists will automatically interchange orders for intermittent infusion (over 30 min) piperacillin/tazobactam to extended infusion (over 4 hours) and adjust the frequency as indicated in the chart below.  The creatinine clearance (CrCl) will be estimated using the Cockroft-Gault or Corcoran-Salazar equation. This plan of action is supported by the MHCS Antimicrobial Stewardship Program.

Exceptions:

If IV line availability is limited because patients are receiving medications that are incompatible with piperacillin/tazobactam, the antibiotic can still be infused over 30 minutes if needed.  In the event this is necessary, the dose will be converted to the indication specific traditional 30 minute infusion dose based on the patient’s estimated renal function as per previously approved renal adjustment protocol.

Examples:

1.      Prescriber orders piperacillin/tazobactam 4.5g q6h.  Dose should be automatically adjusted by the pharmacist to piperacillin/tazobactam 3.375g q8h over 4 hours.

2. Prescriber orders piperacillin/tazobactam 3.375g q6h in a patient on hemodialysis.  Dose should be automatically adjusted by the pharmacist to piperacillin/tazobactam 3.375g q12h over 4 hours.
3. Patient currently being treated with 3.375g q8h over 4 hours for pneumonia with a CrCl of 100 mL/min. The patient loses IV access and only has one line. The nurse has requested to temporarily change piperacillin/tazobactam to the 30 min infusion. Dose should be automatically adjusted by the pharmacist to piperacillin/tazobactam 4.5g q6h over 30 min. Switch back to 3.375g q8h over 4 hours as soon as possible.