Sinai Health Practice Change: Beta-lactam Extended Infusions��Optimizing Meropenem and Piperacillin-Tazobactam Administration to Improve Patient Outcomes

Sinai Health Antimicrobial Stewardship Program

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PK/PD data support prolonged infusions of beta-lactams

• Time > MIC! The longer the drug concentration is above the MIC, the better bacterial killing effect.  
• Prolonging the infusion time is one way we overcome resistance, improve patient outcomes and reduce the need to escalate to broader-spectrum antibiotics. 

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MIC of a more resistant bacteria

MIC of a less resistant bacteria

The green line (3-hour extended infusion) keeps the drug level above the MIC (purple lines) longer than the blue line (30-minute infusion). This improves bacterial killing and is particularly important for more resistant bacteria. 

Green (3hr infusion): time > MIC = 3-5 hrs

Blue (30min infusion): time > MIC = 0.5-1 hrs

Clinical data show benefit of prolonged infusions

Dulhunty JM, et al. JAMA. 2024;332(8):629-637. doi:10.1001/jama.2024.9779

Abdul-Aziz MH et al. JAMA. 2024;332(8):638–648. doi:10.1001/jama.2024.9803

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What is my role?

• The standard infusion time for meropenem and piperacillin-tazobactam for all inpatients will be 3 hours (extended infusion) instead of the traditional 30-minute infusion (usual renal dose adjustments apply)
• Enter orders via the new order sets in PowerChart which contain:

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What will this look like in PowerChart?

How to de-escalate therapy

• Please use our “De-escalation Guide” and flow chart on next slide.

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• To shorten infusion time to 30 min, use “Cancel/Re-order” in PowerChart:

Remember to:

1. Change infuse over from 3 to 30

2. Change unit from hr to min

3. Remove MD NOTES comment

4. Check timing of last dose on eMAR to ensure subsequent doses are scheduled at proper interval

Does the patient still need antibiotics?

Stop antibiotics.

Can the patient be switched to oral antibiotics?

Switch to appropriate oral antibiotic.

Can the antibiotics be changed to a narrowed spectrum?

Narrow antibiotics.

Is the patient clinically stable and improving?

Continue extended (3 hour) infusion.

Is the patient in ICU?

Is the targeted pathogen reporting susceptible dose-dependent (SDD) to piperacillin-tazobactam?

Shorten to intermittent (30 min) infusion

Yes

No

Yes

No

Yes

No

No

No

Yes

Yes

Yes

No

Are the patient’s infection site cultures negative ?

No

Yes

At 48-72h, evaluate patient for de-escalation

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Are there any exceptions for extended infusion protocols?

• One-time doses for patients in specific hospital units (e.g. OR) and in any emergent situations (including septic shock) .
• Central nervous system infections requiring meropenem.
• Medication scheduling and/or drug compatibility conflicts that cannot be resolved with available IV lines.
• Patients with other medical interventions (e.g. PT) that cannot be performed adequately during the IV infusion AND only if administration times cannot be modified to accommodate the intervention.
• Consultation by Antimicrobial Stewardship or Infectious Disease consultant recommending the use of intermittent infusion protocol.

Questions?��Sinai Health Antimicrobial Stewardship Program antimicrobial.stewardship@sinaihealth.ca�

References

1. Abdul-Aziz MH, Sulaiman H, Mat-Nor MB, Rai V, Wong KK, Hasan MS, Abd Rahman AN, Jamal JA, Wallis SC, Lipman J, Staatz CE, Roberts JA. Beta-Lactam Infusion in Severe Sepsis (BLISS): a prospective, two-centre, open-labelled randomised controlled trial of continuous versus intermittent beta-lactam infusion in critically ill patients with severe sepsis. Intensive Care Med. 2016 Oct;42(10):1535-1545. doi: 10.1007/s00134-015-4188-0.
2. Tran NN, Mynatt RP, Kaye KS, Zhao JJ, Pogue JM. Clinical Outcomes With Extended Versus Intermittent Infusion of Anti-Pseudomonal Beta-Lactams in Patients With Gram-Negative Bacteremia. Open Forum Infect Dis. 2023 Mar 27;10(4):ofad170. doi: 10.1093/ofid/ofad170.
3. Monti G, Bradić N, Marzaroli M, et al. Continuous vs Intermittent Meropenem Administration in Critically Ill Patients With Sepsis: The MERCY Randomized Clinical Trial. JAMA. 2023;330(2):141–151. doi:10.1001/jama.2023.10598
4. Dulhunty JM, Brett SJ, De Waele JJ, et al. Continuous vs Intermittent β-Lactam Antibiotic Infusions in Critically Ill Patients With Sepsis: The BLING III Randomized Clinical Trial. JAMA. Published online June 12, 2024. doi:10.1001/jama.2024.9779
5. Abdul-Aziz MH, Hammond NE, Brett SJ, et al. Prolonged vs Intermittent Infusions of β-Lactam Antibiotics in Adults With Sepsis or Septic Shock: A Systematic Review and Meta-Analysis. JAMA. Published online June 12, 2024. doi:10.1001/jama.2024.9803
6. Hong LT, Downes KJ, FakhriRavari A, et al. International consensus recommendations for the use of prolonged-infusion beta-lactam antibiotics: Endorsed by the American College of Clinical Pharmacy, British Society for Antimicrobial Chemotherapy, Cystic Fibrosis Foundation, European Society of Clinical Microbiology and Infectious Diseases, Infectious Diseases Society of America, Society of Critical Care Medicine, and Society of Infectious Diseases Pharmacists. Pharmacotherapy. 2023 Aug;43(8):740-777. doi: 10.1002/phar.2842
7. Wenker SA, Alabdulkarim N, Readman JB, et al. Defining the pharmacokinetic/pharmacodynamic index of piperacillin/tazobactam within a hollow-fibre infection model to determine target attainment in intensive care patients, JAC-Antimicrobial Resistance, 2024;6(2). https://doi.org/10.1093/jacamr/dlae036
8. Kong, D., Roberts, J.A., Lipman, J. et al. A Pooled Pharmacokinetic Analysis for Piperacillin/Tazobactam Across Different Patient Populations: From Premature Infants to the Elderly. Clin Pharmacokinet. 2025;64: 107–126. https://doi.org/10.1007/s40262-024-01460-6