Piperacillin-tazobactam (Zosyn) (IV)

Criteria & Principles

Appropriate Indications for Use:

Inappropriate Indications for Use:

Sepsis of Unknown Etiology Nosocomial Pneumonia Severe/limb-threatening Skin and Soft Tissue Infection (e.g., DFI, necrotizing) Health-care associated/high risk intra-abdominal infection Severe infection with recent history of MDR-pathogen

Community Acquired Pneumonia (standard ceftriaxone +/- azithromycin) Aspiration Pneumonia (standard ampicillin-sulbactam) COPD Exacerbation (standard doxycycline) Community Acquired Intra-abdominal Infection (standard ceftriaxone +/- flagyl) Uncomplicated Skin/soft tissue infection (standard cefazolin=non-purulent OR vancomycin=purulent) Urinary tract infections (standard ceftriaxone) Meningitis (standard ceftriaxone or cefepime)

 

Usual Dose & Administration

Usual Adult Dose

3.375 g IV q8h (administer each dose over 4 hours)

Adjustment of Dose & Administration

Indication-Specific Adjustment

Loading doses:  a 3.375 g to 4.5 g loading dose can be given over 0.5 hours. This approach may be particularly useful to achieve faster target attainment in immunocompromised patients or in patients with previously documented Pseudomonas organisms with higher MIC distribution. The optimal time to start the subsequent extended infusion is 4 hours later in patients with CrCl >20 mL/min and 8 hours later in patients with CrCl <20 mL/min. Of note, administering loading doses has not been shown to decrease mortality or time to clinical improvement compared to initiating therapy with an extended infusion.

Higher doses may be considered in select patients, such as cystic fibrosis patients or critically-ill ICU patients with a known susceptible pathogen not improving on 3.375 g IV q8h. In such cases, piperacillin-tazobactam 4.5 g IV over 4hrs Q8h may be considered (in those with normal renal function)

Extended infusion of piperacillin-tazobactam is preferred at DRAH. Patients with orders for piperacillin-tazobactam for which a 4-hour infusion time may not be practical may receive a traditional standard 30-minute infusion at the discretion of the physician and/or nursing staff. See the "Renal Dysfunction" section for dosing adjustments.

• To avoid inappropriate ordering of q8 or q12 interval traditional infusion, a BPA will fire on pharmacist verification  
• To avoid inappropriate timing transitions from traditional to extended infusion, a BPA will fire on pharmacist verification 
• Clinical pharmacists should be contacted to assist with traditional infusion dosing.  Placing new lines to accommodate extended-infusion PTZ is discouraged

Renal Adjustment

 Dosing adjustments for patients receiving 4-hour extended infusions

	CrCl
	>20 mL/min	<=20 mL/min (including peritoneal or hemodialysis)	CRRT
Piperacillin-tazobactam standard dose	3.375g q8h (4hr)	3.375g q12h (4hr)	3.375g q8h (4hr)
Cystic fibrosis (susceptible organisms; all indications except CNS)* MDR Pseudomonas/Acinetobacter, susceptible to pip/tazo* Necrotizing fasciitis*	4.5g q8h (4hr)	4.5g q12h (4hr)	4.5g q8h (4hr)

*piperacillin-tazobactam 4.5 g IV over 4hrs may be considered in select patients, such as cystic fibrosis patients or critically-ill ICU patients with a known susceptible pathogen not improving on 3.375 g IV q8h

 

Dosing adjustments for patients receiving 30-min traditional infusions

CrCl	Dosing for 30-min infusions
> 40 mL/min	3.375g to 4.5g IV q6h (30-min)
20-40 mL/min, CRRT	2.25g IV q6h (30-min)
< 20 mL/min, hemodialysis	2.25g IV q8h (30-min)

 

Drug-Specific Information

Extended infusion piperacillin-tazobactam dosing was adopted into clinical practice at DUHS in 2013. Exceptions to extended infusion dosing and administration are pediatric patients, patients in the Emergency Department who have not yet been admitted and transferred to the floor, as well as patients receiving piperacillin-tazobactam for surgical prophylaxis in the OR and PACU areas. Ambulatory care clinics may also resort to traditional 30-min infusions upon the discretion of the physician or nursing staff.

Piperacillin/tazobactam and IV Vancomycin Compatibility

• ​The physical compatibility of vancomycin has been evaluated with both branded and generic piperacillin-tazobactam in concentrations typical for extended infusions. Vancomycin concentrations of less than or equal to 7 mg/mL were compatible using simulated Y-site administration with piperacillin-tazobactam 33.75 mg/mL up to 90 mg/mL.
• At DRAH, vancomycin peripheral line concentrations do not exceed 6 mg/mL whereas central line concentrations may be up to 10 mg/mL. Therefore, it can be recommended to Y-site peripheral concentration vancomycin with pip-tazo 3.375g or 4.5g to help resolve medication scheduling issues [Ref: O’Donnell JN, et al. Visual and absorbance analyses of admixtures containing vancomycin and piperacillin-tazobactam at commonly used concentrations. Am J Health-Syst Pharm 2016; 73: 241-6.]

Piperacillin/tazobactam and Lactated Ringers Compatibility

• See pip/tazo and LR memo

Cost Index

$ (1-10)

General Notes

1. Up to date cost information for select antimicrobials is found in the PDF on this page. https://www.customid.org/antimicrobial/antimicrobial-cost-chart
2. Information about how to administer select IV antimicrobials outpatient (OPAT) is found here https://assets.customid.org/OPATchart%20Final.pdf
3. When dosing guidance is provided it is important to note the following:

Fixed (ie non weight-based) doses in adults are historically based on a 70 kg patient. Specific disease states or individual patients may warrant dosages that differ from the above recommendations. Since product-specific criteria for dose adjustment based on creatinine clearance exist, consult product information regarding specific recommendations for dosage adjustment based on estimated creatinine clearance.