UCSF Medical Center Extended Infusion Piperacillin/tazobactam Policy and Procedure

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 Office of Origin: Department of Pharmaceutical Services, Antimicrobial Stewardship Program, Department of Nursing

     I.         PURPOSE

To develop an extended infusion (EI) protocol for inpatients receiving piperacillin/tazobactam with the goal of decreasing the dose of antibiotic needed to achieve equivalent or superior therapeutic target compared to standard short infusion (SI).

   II.         BACKGROUND/JUSTIFICATION

Pharmacokinetic/pharmacodynamic studies have demonstrated that EI dosing of piperacillin/tazobactam achieves target time above concentration goals for adequate empirical and definitive therapy of bacterial infections, including treatment of susceptible Pseudomonas.

III.         REFERENCES

1.         Pharmacist Prescribing Authority:  6.09.09 Medication Management: Pharmacist Prescribing Authority 

2.         Department of Nursing Medication Administration procedure

3.         Department of Nursing IV Pump – Alaris©  Medley with Guardrails procedure

4.         IDMP Website: idmp.ucsf.edu

5.         Lodise TP, Lomaestro B, Rodvold KA, et al. Pharmacodynamic profiling of piperacillin in the presence of tazobactam in patients through the use of population pharmacokinetic models and monte carlo simulations. Antimicrob Agents Chemother 2004;48(12): 4718-4724.

6.         Lodise TP, Lomaestro B, Drusano G. Application of antimicrobial pharmacodynamics concepts into clinical practice: focus on βlactam antibiotics. Pharmacotherapy2006;26:13201332.

7.         Shea KM, Cheatham SC, Wack MF, et al. Steadystate pharmacokinetics and pharmacodynamics of piperacillin/tazobactam administered by prolonged infusion in hospitalised patients. Int J Antimicrob Agents 2009;34(5):42933.

8.         Shea KM, Cheatham SC, Smith DW, et al. Comparative pharmacodynamics of intermittent and prolonged infusions of piperacillin/tazobactam using Monte Carlo simulations and steadystate pharmacokinetic data from hospitalized patients. Ann Pharmacother 2009;43(11):174754.

9.         Felton TW, Hope WW, Lomaestro BM, et al. Population pharmacokinetics of extendedinfusion piperacillintazobactam in hospitalized patients with nosocomial infections. Antimicrob Agents Chemother 2012;56(8):408794.

10.      Lodise TP, Lomaestro B, Drusano G. Piperacillintazobactam for Pseudomonas aeruginosa infection: clinical implications of an extendedinfusion dosing strategy. Clin Infect Dis2007;44(3):35763.

11.      Falagas ME, Tansarli GS, Ikawa K, et al. Clinical outcomes with extended or continuous versus short-term intravenous infusion of carbapenems and piperacillin/tazobactam: a systematic review and meta-analysis. Clin Infect Dis 2013;56:272-282.

12.      Lorente L, Jimenez A, Martin MM, et al. Clinical cure of ventilator-associated pneumona treated with piperacillin/tazobactam administered by continuous or intermittent infusion.  Int J Antimicrob Agents 2009;33:464-8

13.      Dulhunty JM, Roberts JA, Davis JS, et al. A multicenter randomized trial of continuous versus intermittent beta-lactam infusion in severe sepsis. Am J Respir Crit Care Med 2015;192(11):1298-1305.

14.      Dulhunty JM, Roberts JA, Davis JS, et al. Continuous infusion of beta-lactam antibiotics in severe sepsis: a multi-center double-blind, randomized controlled trial. Clin Infect Dis 2013;56:236-244.

15.      Xamplas R, Itokazu G, Glowacki R, et al.Implementation of an extended-infusion piperacillin/tazobactam program at an urban teaching hospital. Am J Health Syst Pharm 2010;67:622–8.

16.      Patel N, Scheetz MH, Drusano GL, et al. Identification of optimal renal dosage adjustments for traditional and extendedinfusion piperacillin/tazobactam dosing regimens in hospitalized patients. Antimicrob Agents Chemother2010;54(1): 46065.

17.      Trissel, LA. Handbook on Injectable Drugs16th Edition. Bethesda, Maryland: American Society of Health-System Pharmacist, 2011. Print

 IV.         POLICY

a. Inpatients being treated with piperacillin/tazobactam will receive EI unless the patient meets the exceptions stated below. 

b. Exclusion Criteria (These patients should receive piperacillin/tazobactam SI unless otherwise noted):

                                          i.         Pediatric patients admitted to Benioff Children’s Hospital

                                         ii.         Patients with creatinine clearance of < 20ml/min, not on continuous renal replacement therapy (CRRT)

                                       iii.         Patients on intermittent hemodialysis (iHD). Note that patients on continuous renal replacement therapy should get EI dosing unless meeting other exclusion criteria.

                                       iv.         Patients with infection or colonization with gram-negative bacteria intermediate or resistant to piperacillin/tazobactam within the last 60 days

a)  Consult with Infectious Diseases or Antimicrobial Stewardship for consideration of alternative therapies.

                                         v.         Patients with cystic fibrosis

                                       vi.         Patients stationed in the emergency department, operating room, peri-              procedural areas, or post anesthesia care units

                                      vii.         Patients with insufficient intravenous access

   V.         PROCEDURES

a.     Definitions

                                          i.         Extended intravenous infusion (EI): Infusion over 4 hours

                                         ii.         Short intravenous infusion (SI): Infusion over 30 minutes

                                       iii.         Continuous renal replacement therapy (CRRT)

                                       iv.         Intermittent Hemodialysis (iHD)

b.     Responsibilities

i.    Provider ordering

a) Determine whether the patient is eligible for EI. For patients meeting exclusion criteria discussed in section IV, subsection b, piperacillin/tazobactam should be ordered as a SI with appropriate dosing selected for renal function. All other patients should get EI dosing.

b) For patients ordered to receive EI, determine when the last dose of piperacillin/tazobactam was administered.

                                                                i)         Patients who have not received a dose of piperacillin/tazobactam SI within 6 hours or EI started within 10 hours: piperacillin/tazobactam should be ordered as EI with loading dose. Please consult with a clinical pharmacist in the case of a patient previously on EI piperacillin/tazobactam with last dose started 10-14 hours ago.

                                                               ii)         Patients who have received a dose of piperacillin/tazobactam SI within 6 hours or EI started within 10 hours: piperacillin/tazobactam should be ordered as EI without loading dose.       

ii.   Pharmacist Verification

a) Review each order for appropriateness, including but not limited to:

                                                                i)         Allergies

                                                               ii)         Indication

                                                             iii)         Site of infection

                                                             iv)         Suspected pathogens

                                                               v)         Drug compatibilities

                                                             vi)         Timing of administration

b) Replace SI orders with EI orders, unless patient meets exclusion criteria outlined in Section IV, Subsection b.

c) Replace EI orders with SI orders, as outlined in Section VI for patients meeting exclusion criteria outlined in Section IV, Subsection b.

d) Assess need for loading dose of piperacillin/tazobactam based on last piperacillin/tazobactam administration time.

                                                                i)         Patients who have not received a dose of piperacillin/tazobactam SI within 6 hours or EI started within 10 hours: order a piperacillin/tazobactam loading dose as outlined in Section VI, if not already ordered by the provider. If the last dose of piperacillin/tazobactam EI was started 10-14 hours ago, please use best judgement based on renal function, indication, and clinical status when assessing need for loading dose. If assistance is needed, consult the Antimicrobial Stewardship Program pharmacist.

                                                               ii)         Patients who have received a dose of piperacillin/tazobactam SI within 6 hours or EI started within 10 hours: no loading dose is needed. Cancel the loading dose if ordered by the provider.

e) Adjust timing of piperacillin/tazobactam, depending on when the last dose, if any, was administered.

f) Adjust timing of piperacillin/tazobactam with vancomycin and other IV medications to avoid compatibility issues, if applicable. See Appendix I.

iii.  Nursing Administration

a) Administer medication following the Medication Administration and IV pump Alaris Medley with Guardrails nursing procedures.

b) To administer a STAT IV medication that is incompatible with piperacillin/tazobactam, stop EI piperacillin/tazobactam, flush the line, and administer the STAT IV medication. Then, resume EI piperacillin/tazobactam.

 VI.         DOSING RECOMMENDATIONS

Extended Infusion ( 4 hour infusion) in 100ml 0.9% NaCl

 

CrCl > 20 ml/min or CRRT

Loading Dose (LD), if indicated*

4.5 gm IV over 30 min x 1

Maintenance Dose (starting 4 hrs after loading dose, if indicated)

4.5 gm IV over 4 hr  q8h

 

* Only give a LD if there has not been a SI dose within 6 hours or an EI dose started within 10 hours

 

Short infusion (30-minute infusion)  in 100 ml 0.9% NaCl

 

CrCl ≥ 50 ml/min

CrCl 10-50 ml/min

CrCl < 10 ml/min

Dialysis (HD or CRRT)

General infections

3.375 gm IV Q6h

3.375 gm IV Q6-8h

2.25 gm IV Q8h

HD: 2.25 gm IVq8h

CRRT: 4.5 gm IV Q8h or 3.375 gm IV Q6h

Documented/suspected Pseudomonas infections

CrCl > 20 ml/min:

4.5 gm IV Q6h

CrCl < 20 ml/min: 2.25 gm IV Q8h

HD: 2.25 gm IVq8h

CRRT: 4.5 gm IV Q8h or 3.375 gm IV Q6h

 

APPENDIX I:   Common Y-site IV incompatibilitiesa

Known incompatible agents

Acyclovir

Amiodarone HCL

Amphotericin B (cholesteryl and conventional colloidal)

Caspofungin

Chlorpromazine

Ciprofloxacin

Cisplatin

Daunorubicin

Decarbazine

Dobutamine

Doxorubicin

Doxycycline

Droperidol

Diltiazem

Famotidine

Ganciclovir

Gemcitabine

Haloperidol

Hydralazine

Hydroxyzine

Idarubicin

Insulin regular

Levofloxacin

Mitomycin

Mitoxantrone

Minocycline

Nalbuphine

Phenytoin

Prochlorperazine

Promethazine

Tobramycinb

Variable compatibility

Azithromycin

Cisatracurium

Gentamicinb

Pantoprazole

Vancomycinc

 

 

a List is not comprehensive. Refer to Micromedex or LexiComp for more compatibility information.

b Avoid mixing aminoglycosides & penicillin in the same bag and avoid infusing concurrently through same line.

c Compatibility of vancomycin and piperacillin/tazobactam is concentration and formulation dependent. Avoid infusing vancomycin and piperacillin/tazobactam through the same lumen concurrently if possible (i.e. administer vancomycin and piperacillin/tazobactam infusion through separate lumens or administer vancomycin prior to the piperacillin/tazobactam 4-hour infusion). For additional information or clarification, call inpatient pharmacy.