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Document Title: Document Number

Administration of Beta-Lactam Antibiotics (Piperacillin/Tazobactam & Meropenem) by Extended Infusion in Adult Critical Care Patients 508

Version Number Name and date and version number of previous document (if applicable): Document author(s):

Document developed in consultation with: Staff with overall responsibility for development, implementation and review: Development / this review period:

1.0 N/A Dean Burns (Consultant, Emergency Medicine and Critical Care) Sue Lee (Lead Pharmacist, Critical Care) Rohinton Mulla (Consultant Microbiologist) Critical Care Consultants

July 2020

Date approved by the Policy Approval Group/Clinical Guidelines Committee / DTC on behalf of the Trust Board: Chief Executive / Chair Clinical Guidelines /Chief Pharmacist Signature: Date for next review:

Date document was Equality Analysed:

Target Audience:

Key Words:

Associated Trust Documents:

Reason for current amendments:

1st July 2020

Dr J Kapadia

July 2023 N/A

Beta-Lactam/Piperacillin-Tazobactam/Meropenem/ Continuous/Infusion 232: Antimicrobial Prescribing Guidelines for Adult Patients 2016 257: The management of neutropenic sepsis in adult oncology/haematology patients 2019 PGD 155: Tazocin for Neutropenic Sepsis 2018

Contents

Summary.................................................................................Page 3 Aim.........................................................................................Page 3 Background.............................................................................Page 3 Indications..............................................................................Page 3 Contraindications....................................................................Page 3 Allergy Status.........................................................................Page 3 Loading Dose..........................................................................Page 4 Tables for Doses, including Renal Impairment............................Page 4 Stability..................................................................................Page 5 Compatibility (Y-site)................................................................Page 5 Conversion to Intermittent Infusion...........................................Page 5 Training.................................................................................Page 6 Appendix 1 (Summary table).....................................................Page 7 References..............................................................................Page 9

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Summary This guideline is for use in adult critical care patients only. This includes patients in the Intensive Therapy Unit (ITU) and High Dependency Unit (HDU). Aim The aim of this guideline is to establish a safe practice for the use of Extended Infusion Beta-Lactam Antibiotics in the Critical Care Units at Luton and Dunstable University Hospital NHS Foundation Trust. Background Historically, most antibiotics have been administered by either bolus or intermittent infusion. Beta-Lactam antibiotics exhibit time-dependent bactericidal activity and pharmacokinetic / pharmacodynamic studies have shown that extended or continuous infusions will maintain the drug serum concentrations above the minimum inhibitory concentration (MIC) of targeted pathogens for a more optimal time-frame over a 24 hour period. Furthermore, some studies have found that prolonged infusions of broad spectrum beta-lactam antibiotics (carbapenems, penicillins and cephalosporins) significantly reduced all-cause mortality in adults with sepsis compared with short-term infusions. No data to date has demonstrated inferiority of extended infusions compared to traditional dosing, and extended infusions are already the standard method of administration in many Critical Care Units, both in UK and other countries. Indication Severe infection or sepsis in critical care patients when beta-lactams are indicated. Contraindications Patients on general wards, not critical care Patients on intermittent haemodialysis or peritoneal dialysis Allergy Status Piperacillin-Tazobactam : DO NOT USE IN PENICILLIN ALLERGY Meropenem : USE WITH CAUTION IN PENICILLIN ALLERGY

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First antibiotic dose / loading dose

To reduce any potential delay in achieving therapeutic concentrations, the first dose should be administered as a STAT (either a slow bolus or 30 minute infusion). The STAT dose should not be considered as the first dose of the multiple daily dosing schedules.

The first extended infusion dose should be started immediately after the loading dose.

Patients who have already received a dose of piperacillin/tazobactam or meropenem in the last 6 hours do not need an additional loading dose and the extended infusion can be started immediately.

Consider prescribing doses indicated for normal renal function in all patients for the first 24-48 hours, regardless of degree of renal impairment.

In certain patients, intravenous (IV) line access may restrict the use of extended infusions, in which case the doses should be given as per Trust intravenous administration guidelines. However, please also refer to the compatibility section or the ward pharmacist for further advice

Extended Administration over 4 hours (Unlicensed)

Piperacillin-Tazobactam

Initial Bolus dose

Maintenance Dose (over 4 hours)

(in 20ml WFI)*

Dilute dose in 50ml of either Sodium Chloride 0.9% or Glucose 5%.

over 30 minutes

Infuse over 4 hours via peripheral or central line

Renal Function (creatinine clearance ml/min)

Haemo(dia)filtration exchange rate

Independent of

>40

renal function

mL/min

4.5grams

4.5g

STAT

6hrly

*(WFI = Water for Injection)

10-40 ml/min 4.5g 8hrly

2.4L/hr

4.5g 6hrly

Meropenem

Initial Bolus dose (over 3-5 minutes)

Independent of renal function

1gram STAT

Maintenance Dose (over 4 hours)

Dilute dose in 50ml of Sodium Chloride 0.9%

Infuse over 4 hours via peripheral or central line

Renal Function (creatinine clearance ml/min)

Haemo(dia)filtration exchange rate

>50 mL/min

26-50

10-25

HD

CRRT

CRRT

CRRT

ml/min

mL/min

1.5L/hr

1.6-3L/hr

>3.0L/hr

1g

500mg

500mg 1g 24hrly

500mg

500mg

1g

8hrly

6hrly

8hrly

(post HD)

8hrly

6hrly

8hrly

(Doses may differ from those in the Renal Drug Database- additional reference sources used)

NB: For patients with Meningitis, Cystic Fibrosis or infections requiring MIC of 4mg/L, eg Listeria, Meropenem doses should be doubled.

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Stability

Piperacillin/ Tazobactam ? Each 4.5g vial should be reconstituted with 20ml of Water for Injections or Sodium Chloride 0.9%. ? The contents of the vial should then be made up to 50ml in a syringe with either Sodium Chloride 0.9% or Glucose 5%. ? Infuse over 4 hours (unlicensed) via either peripheral or central line. Start infusion as soon as possible after preparation to reduce risk of microbial contamination. The diluted solution is stable for 24 hours at 25?C.

Meropenem ? Each 1g vial should be reconstituted with 20ml of Sodium Chloride 0.9% as per manufacturer's instructions. (500mg vial in 10ml of Sodium Chloride 0.9%)

? The contents of the vial should then be made up to 50ml in a syringe with Sodium Chloride 0.9%.

? Infuse over 4 hours (unlicensed) via either peripheral or central line. Start infusion as soon as possible after preparation to reduce risk of microbial contamination. The diluted solution is stable for 6 hours at 25?C.

Compatibility (Y-site)

Piperacillin/ Tazobactam in sodium chloride 0.9%

Compatibility

Aminophylline, co-trimoxazole, fluconazole, metronidazole,

morphine.

Incompatibility

Aciclovir, amiodarone, caspofungin, ciprofloxacin, dobutamine,

pantoprazole, vancomycin, gentamicin, amikacin, tobramycin,

sodium bicarbonate, sodium lactate (Hartmann's).

Meropenem in sodium chloride 0.9%

Compatibility

Aminophylline, anidulafungin, caspofungin, ciclosporin,

dexamethasone, digoxin, fluconazole, furosemide,

gentamicin, heparin, insulin human soluble, linezolid,

magnesium sulfate, metoclopramide, morphine sulfate,

phenobarbital sodium, potassium chloride, ranitidine,

vancomycin.

Incompatibility

Aciclovir, amphotericin, calcium chloride, calcium gluconate,

diazepam, doxycycline, ondansetron, pantoprazole,

zidovudine.

Converting to intermittent infusions or at discharge from Critical Care

All infusions should have completed prior to discharge from Critical Care. Infusion rates may be increased to support discharge from the unit provided the maximum rate is not exceeded. If the patient is to continue beta-lactam antibiotics after

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