Meropenem or Piperacillin-tazobactam Continuous infusions in Adult Critical Care Areas

Publication: 11/01/2019  
Next review: 18/03/2025  
Clinical Guideline
ID: 5867 
Approved By: Improving Antimicrobial Prescribing Group 
Copyright© Leeds Teaching Hospitals NHS Trust 2022  


This Clinical Guideline is intended for use by healthcare professionals within Leeds unless otherwise stated.
For healthcare professionals in other trusts, please ensure that you consult relevant local and national guidance.

Guidelines for Extended or Continuous infusions of Meropenem or Piperacillin-tazobactam in Adult Critical Care Areas

This document provides guidance for critical care prescribers regarding the situations in which it would be appropriate to consider the use of continuous infusions of meropenem or piperacillin-tazobactam. This document is supplementary to, and should be used in conjunction with, existing LTHT antimicrobial guidelines for treatment, and the product specific summary of product characteristics.

The use of continuous infusions of meropenem or piperacillin-tazobactam can be considered within its currently approved LTHT Drugs and Therapeutics Committee [DTC] application; other indications will require chairman’s action.

Back to top

Drug Information


Piperacillin-tazobactam and meropenem are beta lactam antibiotics whose efficacy is dependent upon the percentage of time their free plasma concentration exceeds the pathogen’s minimum inhibitory concentration (MIC). The higher this percentage, the higher the effectiveness. In patients with normal renal function the fluctuation in beta lactam concentration improves when prolonged infusions are used compared to standard short term infusions or bolus doses.

A systematic review and meta-analysis compared prolonged versus short term intravenous infusion of antipseudomonal beta lactams in patients with sepsis. The authors concluded that critically ill patients with severe sepsis receiving prolonged infusions had a lower mortality compared to those receiving short infusions. - Risk Ratio 0.7, 95% CI 0.56-0.87.1

The Surviving Sepsis Campaign Guidelines 2021 recommend prolonged infusion of beta-lactams for maintenance (after an initial bolus) over conventional bolus infusion for adults with sepsis or septic shock 2

Piperacillin-tazobactam and meropenem are widely used in the critical care patient group. This guideline does not intend to affect the indications, or dosage of these antibiotics, rather it alters method of administration with the intention to improve the efficacy of these agents compared to previous practice.

Back to top

Antimicrobial Activity

Not applicable to this guideline.

Back to top

Dose/Routes of administration





1g by  intravenous injection over 5minutes
2g in selected cases***

4.5g by intravenous injection or short infusion (over 30-60minutes)


Followed (within 2 hrs) by


1g 8-hourly
Infused over 3hrs
2g 8-hourly regimen can be used in selected cases *** 

4.5g 8-hourly, infused over 8 hours     OR
4.5g 6-hourly, infused over 6hours (if neutropenic sepsis, severe pneumonia, suspected /proven pseudomonas infection, or where the organism is specified as “sensitive/increased exposure**)

Renal  Impairment

CrCl 20-50ml/min:  
1g (or 2g***) 12-hourly, infused over 3hours

CrCl <20ml/min  
500mg (or 1g***) 12-hourly, infused over 3hours

1g (or 2g***) 8-hourly, infused over 3hours

CrCl 20-40ml/min  
4.5g 8-hourly,  infused over 8 hours

CrCl <20ml/min  
4.5g 12-hourly, infused over 12 hours

4.5g 6 to 8-hourly,  infused over 6 to 8 hours (depending on indication - see above**)

Infusion method

500mg - 1g in 50ml Sodium Chloride 0.9%
2g in 100mL Sodium Chloride 0.9% ***
All infusions are over 3 hours due to stability.

4.5g in 50mL sodium chloride 0.9%
Infused over

  • QDS (6-hourly) 6hours
  • TDS (8-hourly) 8hours
  • BD   (12-hourly) 12hours

* Loading doses can be omitted if treatment was already started elsewhere
** Use of piperacillin-tazobactam for severe pneumonia requires microbiological approval/code

***A regimen based on a 2g 8-hourly dosage can be used in selected cases e.g. cystic fibrosis patient with pseudomonal infection

The choice of antibiotic therapy remains as per LTHT guidelines, or subject to microbiology approval (with approval code). The information in the table solely covers infusion methodology, and dosage adjustments due to renal impairment and continuous dialysis (CVVHD).

Patients transferred into critical care during treatment should change to prolonged/continuous infusions for the remaining maintenance doses

Patients transferred out of critical care during treatment should change back to bolus or short infusion as per usual practice on the transfer ward.

To aid prescribing, protocols exist on eMEDs. Each prescription includes guidance in the event that a patient is transferred out of critical care i.e. revert to usual method of administration for that area. Prescribers still need to include the indication and duration on the prescriptions and should follow the usual trust infection guidelines.

No adjustment required

No Adjustment required

Back to top

Therapeutic Drug Monitoring (checking levels)

Not applicable

Back to top


Not applicable

Back to top

Allergy advice

Piperacillin-Tazobactam and meropenem are contra-indicated in patients with a history of acute severe allergic reaction to any other beta-lactam active substances (e.g. penicillins, cephalosporins, monobactams or carbapenems). Clinical microbiology advice should be sought if necessary.
See LTH Assessment and Management of a Patient presenting with a History of Penicillin Allergy  for additional guidance.

Back to top

Key interactions (include BNF black dot)

None applicable

Back to top

Y Site Compatibility and Route of Administration

Infusions should be prepared immediately prior to administration, and never in advance.

Meropenem and piperacillin-tazobactam infusions as described in this guidance are suitable for either peripheral or central intravenous administration.

Venous access is often limited in critically ill patients, and it may be necessary to mix drug infusions at the point of administration i.e. infuse down the same intravenous line.

To ensure safety and efficacy practitioners should confirm if medicines are chemically & physically compatible with each other (Y Site compatibility), before proceeding with administration. Medicines that are Y Site incompatible, or where information is unavailable, should not be mixed during infusion. This information is available via Medusa, your ward pharmacist, or Medicines Information (Ex 65377)

Back to top

Drug Indications

Prophylaxis indications in LTHT

This guideline does not cover the use of these antibiotics for prophylaxis. Standard short term infusions or bolus injections should be used in this context

Back to top

Treatment indications in LTHT

The following patients are excluded from prolonged or continuous infusions

  • Patients outside of critical care wards
  • Patients undergoing intermittent renal replacement therapy e.g. haemodialysis, CAPD
  • Patients receiving these antibiotics for prophylaxis

This guideline covers the majority of situations where piperacillin-tazobactam or meropenem are prescribed for patients in adult critical care areas. i.e.

  • Sepsis Management Guidelines (including BUFALO)
  • Hospital-Acquired Pneumonia
  • Ventilator-associated Pneumonia
  • Intra-abdominal Infections in Adults
  • Neutropenic Sepsis (adults)
  • Skin and Soft tissue Infection - Including Cellulitis, Surgical Wound Infections and Necrotising Infections (Fasciitis) in Adults

The infection guidelines should always be referred to for the choice of anti-microbial; this guideline only covers how to give as an extended or continuous infusion on critical care wards.

In cases outside of the indications listed above and/or those involving resistant bacteria or difficult to reach sites of infection - microbiology approval (with approval code) is required.

Back to top

Prescribing restrictions

This guideline solely covers the administration of these antibiotics and does not replace existing LTHT infection guidelines. Prescriptions for extended or continuous infusions of meropenem or piperacillin-tazobactam must follow LTHT infection guidelines, or be subject to microbiology approval (with continued requirement for an approval code).

The dosage information in the prescribing table solely covers the recommended infusion periods, and any dosage adjustments, common in critical care, due to renal impairment and/or continuous renal replacement therapy (CVVHD).


Record: 5867
Clinical condition:
Target patient group:
Target professional group(s): Secondary Care Doctors
Secondary Care Nurses
Adapted from:

Evidence base

  1. Vardakos KZ, Voulgaris GL, Maliaros M, Samonis G, Falagas ME. Prolonged versus short-term intravenous infusion of antipseudomonal β-lactams for patients with sepsis: a systematic review and meta-analysis of randomised trials. Lancet 2018;18:108-120
  2. Evans L, et al. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock 2021. Critical Care Medicine: November 2021 - Volume 49 - Issue 11 - p e1063-e1143
  3. Intensive Care Society / British Renal Society / The Renal Association.  Clinical Practice Guidelines :  Guidelines Renal Replacement Therapy for Critically Unwell Adult Patients: Guidelines for best practice and service resilience during COVID-19 Accessed on 13/12/2021 at

Approved By

Improving Antimicrobial Prescribing Group

Document history

LHP version 2.0

Related information

Not supplied

Equity and Diversity

The Leeds Teaching Hospitals NHS Trust is committed to ensuring that the way that we provide services and the way we recruit and treat staff reflects individual needs, promotes equality and does not discriminate unfairly against any particular individual or group.