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

• Drug Information
• Introduction
• Antimicrobial activity
• Dose/Routes of administration
• Therapeutic Drug Monitoring (checking levels)
• Pharmacokinetics
• Allergy advice
• Key interactions (include BNF black dot)
• Y Site Compatibility and Route of Administration
• Drug Indications
• Prophylaxis indications in LTHT
• Treatment indications in LTHT
• Prescribing restrictions

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.

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Drug Information

Introduction

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.

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Antimicrobial Activity

Not applicable to this guideline.

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Dose/Routes of administration

* 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.

DOSE IN OBESITY
No adjustment required

DOSE IN LIVER FAILURE
No Adjustment required

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Therapeutic Drug Monitoring (checking levels)

Not applicable

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Pharmacokinetics

Not applicable

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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.

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Key interactions (include BNF black dot)

None applicable

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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)

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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

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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.

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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).